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Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the aberrant production of a broad and heterogenous group of autoantibodies. Even though the presence of autoantibodies in SLE has been known, for more than 60 years, still nowadays a great effort is being made to understand the pathogenetic, diagnostic, and prognostic meaning of such autoantibodies. Antibodies to ds-DNA are useful for the diagnosis of SLE, to monitor the disease activity, and correlate with renal and central nervous involvements. Anti-Sm antibodies are highly specific for SLE. Anti-nucleosome antibodies are an excellent marker for SLE and good predictors of flares in quiescent lupus. Anti-histone antibodies characterize drug-induced lupus, while anti-SSA/Ro and anti-SSB/La antibodies are associated with neonatal lupus erythematosus and photosensitivity. Anti-ribosomal P antibodies play a role in neuropsychiatric lupus, but their association with clinical manifestations is still unclear. Anti-phospholipid antibodies are associated with the anti-phospholipid syndrome, cerebral vascular disease, and neuropsychiatric lupus. Anti-C1q antibodies amplify glomerular injury, and the elevation of their titers may predict renal flares. Anti-RNP antibodies are a marker of Sharp's syndrome but can be found in SLE as well. Anti-PCNA antibodies are present in 5–10% of SLE patients especially those with arthritis and hypocomplementemia.
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Review Article
Serology of Lupus Erythematosus: Correlation between
Immunopathological Features and Clinical Aspects
Emanuele Cozzani, Massimo Drosera, Giulia Gasparini, and Aurora Parodi
Di.S.Sal, Section of Dermatology, IRCCS Azienda Ospedaliera, Universitaria San Martino-IST, 16132 Genoa, Italy
Correspondence should be addressed to Emanuele Cozzani; emanuele.cozzani@unige.it
Received September ; Accepted December ; Published February
Academic Editor: Juan-Manuel Anaya
Copyright © Emanuele Cozzani et al. is is an open access article distributed under the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly
cited.
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the aberrant production of a broad and
heterogenous group of autoantibodies. Even though the presence of autoantibodies in SLE has been known, for more than
years, still nowadays a great eort is being made to understand the pathogenetic, diagnostic, and prognostic meaning of such
autoantibodies. Antibodies to ds-DNA are useful for the diagnosis of SLE, to monitor the disease activity, and correlate with renal
and central nervous involvements. Anti-Sm antibodies are highly specic for SLE. Anti-nucleosome antibodies are an excellent
marker for SLE and good predictors of ares in quiescent lupus. Anti-histone antibodies characterize drug-induced lupus, while
anti-SSA/Ro and anti-SSB/La antibodies are associated with neonatal lupus erythematosus and photosensitivity. Anti-ribosomal P
antibodies play a role in neuropsychiatric lupus, but their association with clinical manifestations is still unclear. Anti-phospholipid
antibodies are associated with the anti-phospholipid syndrome, cerebral vascular disease, and neuropsychiatric lupus. Anti-Cq
antibodies amplify glomerular injury, and the elevation of their titers may predict renal ares. Anti-RNP antibodies are a marker
of Sharp's syndrome but can be found in SLE as well. Anti-PCNA antibodies are present in –% of SLE patients especially those
with arthritis and hypocomplementemia.
1. Introduction
Systemic lupus erythematosus (SLE) is an autoimmune dis-
ease characterized by the presence of autoreactive B and T
cells, responsible for the aberrant production of a broad and
heterogeneous group of autoantibodies (Ta ble ). Indeed, in
Sherer et al. reported that one hundred sixteen autoan-
tibodies have been described in SLE patients []. In SLE, espe-
cially in its systemic form (SLE), autoantibodies directed to
nuclear (ANAs), cytoplasmtic, and cellular membrane anti-
gens are considered the serological hallmark. ANAs consist
of various types of autoantibodies characterized by dierent
antigen specicities. ese nuclear antigens include single
strand (ss) and double strand (ds) DNA (deoxyribonucleic
acid), histone proteins, nucleosome (histone-DNA complex),
centromere proteins, and extractable nuclear antigens (ENA)
(Smith antigen (Sm), Ro, La, ribonucleoprotein (RNP), etc.).
ANAs are present in about % of SLE patients with an active
disease. In patients with prevalent cutaneous lesions, ANAs
have been found positive in % of cases.
erefore, considering the very wide spectrum of dis-
covered autoantibodies, the aim of the present paper is to
highlight the most promising and signicant ones from both
immunopathologic and clinical perspectives.
e presence of autoantibodies in SLE was envisaged
when lupus phenomenon was described by Hargraves et al.
in [ ] and then proven when it was understood that it
was due to neutrophil phagocytosis of cell nuclei opsonised
by autoantibodies. In , antibodies to DNA were identied
[ ] and in Tan and Kunkel found autoantibodies directed
to antigens dierent from DNA and described the anti-Sm
antibodies [ ].
Even though the presence of autoantibodies in SLE
has been known for more than years, still nowadays a
great eort is being made to understand the pathogenetic,
diagnostic, and prognostic meaning of such autoantibodies.
In particular, studies have focused on ANAs, anti-Cq anti-
bodies, and anti-phospholipid antibodies.
Demonstrating the pathogenic role of autoantibodies is
an arduous task; nevertheless recent data from murine, and
Hindawi Publishing Corporation
Autoimmune Diseases
Volume 2014, Article ID 321359, 13 pages
http://dx.doi.org/10.1155/2014/321359
Autoimmune Diseases
T : Correlation between antibodies reactivity lupus subtypes and diagnostic utility.
Antibody Target Diagnostic utility Associated lupus subtypes
(prevalence) Other associated diseases References
ANAs e cell nucleus High sensitivity, but specicity is
low
SLE (%)
LN (%)
MCTD
Drug-induced lupus
Discoid lupus (%)
Hepatic diseases (autoimmune hepatitis
A), malignancies, chronic infections,
thyroid diseases, elderly people, SS, SSc,
PM, DM, juvenile chronic arthritis,
Felty's syndrome, relapsing
polychondritis, and rheumatoid arthritis
[ , , ]
Anti-dsDNA Double strand DNA
High sensitivity and specicity
for SLE. Correlate with disease
activity
SLE (–%)
LN (%)
NPSLE (, –, %)
RA, HIV and parvovirus B infections,
myeloma, and type autoimmune
hepatitis
[ , , – ]
Anti-Sm Sm Low sensitivity, but high
specicity for SLE
SLE (–%)
LN (%)
MCTD (%)
EBV infections [ , ,, ]
Anti-nucleosome Nuclesome
High sensitivity and specicity
for SLE. Correlate with disease
activity
SLE (–%)
LN (–%)
MTCD (%)
RA, SSc, and SS [ , , , ]
Anti-histone Histone Low IgM
Higher IgG
SLE (%)
LN (%)
Anti-HA and Anti-Hb specic
for SLE induced by drugs
(–%)
Rheumatoid arthritis, SSc, PBC ,
Alzheimer's disease, dementia, and
infections
[ , , , ]
Anti-SSA/Ro SSA/Ro (proteins
/ kD) High prognostic value for NLE in
pregnant women
SLE (%)
LN (%)
NLE (especially CHB) (%)
SCLE (–%)
Discoid Lupus (–%)
SSc, IIM ,PBC,RA,andSS [ , , – ]
Anti-SSB/La SSB/La Moderate
SLE (%)
LN (%)
Protective for LN
SCLE (%)
NLE (%)
SS [ ,,, ]
Anti-ribosomal P Ribosomes Moderate
SLE (–%)
LN (%)
NPSLE (especially psychosis and
depression) (%)
Hepatic diseases, malignancies, and RA [ , ,, ]
Autoimmune Diseases
T : C on tinue d.
Antibody Target Diagnostic utility Associated lupus subtypes
(prevalence) Other associated diseases References
Anti-phospholipid
Phospholipids (of
cardiolipin, LACs are
the most important
ones)
High if Anti-PL syndrome is
suspected
SLE (–%)
LN (–%)
Anti-PL syndrome: venous
thrombosis, arterial thrombosis,
recurrent pregnancy loss,
thrombocytopenia and
haemolytic anaemia, livedo
reticularis, and skin ulcers.
Other autoimmune diseases, infections,
malignancies, and drug-induced
disorders, rheumatoid arthritis
[ ,, ]
Anti-Cq Cq Low but useful to monitor
evolution of LE nephritis
SLE (–%)
LN (–%)
CLE (%)
Hypocomplementemic urticarial
vasculitis syndrome, rheumatoid
arthritis, and renal disease
[ ,, ]
Anti-RNP RNP Unclear SLE (–%)
MCTD (%)
Sharp's syndrome
scleroderma, polymyositis,
rheumatoid arthritis,
SSc, Sj ̈
ogren's syndrome
[ ,, ]
Anti-PCNA PCNA Low SLE (–%) Chronic hepatitis B and C [ , ]
1In biology, Sm proteins are a family of RNA-binding proteins found in virtually every cellular organism.
A nucleosome is the basic unit of DNA packaging in eukaryotes, consisting of a segment of DNA wound in sequence around eight histone protein cores.
Primary biliary cirrhosis.
Ro is a ribonuclear protein containing small uridine-rich nucleic acids known. Protein KD is located into the nucleus and nucleolus, while protein is located into the cytoplasm.
Idiopathic inammatory myopathies.
SSB/La particle is a – kDa nuclear phosphoprotein composed of distinct regions of and kDa.
P, P, and P of , , and kDa, respectively, of the S subunit.
Anionic phospholipis including cardiolipin (CL), LA, phophatidylserine (PS), phsphatidylinositol (PI), and phosphatidic acid (PA).
Cq is a cationic glycoprotein of – kDa which binds to the Fc portions of immunoglobulins in immune complexes to initiate complement activation via the classical pathway.
ribonucleoproteins: of kDa (U), kDa (protein A), and kDa (protein C), respectively.
Anti-proliferating cell nuclear antigen.
Autoimmune Diseases
humanmodelshaveclariedthekeyroleofautoantibodiesin
severe organ involvements, such as nephritis and neuropsy-
chiatric dysfunctions [ ]. Common autoantibody-mediated
mechanisms of damage in SLE include immune complex-
mediate damage, cell surface binding and cytotoxicity, reac-
tivity with autoantigens expressed on apoptotic or activated
cell surface, penetration into living cells, and binding to cross-
reactive extracellular molecules [].
Beyond elucidating the mechanisms behind the disease,
understanding the pathogenetic role of autoantibodies, might
have therapeutic implications. Indeed, in a recent article
Diamond et al., aer discovering the antigenic specicity of
a subset of anti-DNA antibodies, hypothesized a potential
therapeutic strategy, using peptides to block the antigen-
binding site of the pathogenetic antibody [ ].
Pisetsky gives another extremely interesting perspective,
based on dierent sources [ – ], on the role of ANAs
in autoimmune diseases, hypothesizing a protective role of
such antibodies [ ]. ANAs would prevent the disease by
inhibiting the immunological activity of nuclear antigens,
promoting their clearance in a nonphlogistic way or blocking
the formation of immune complexes. Indeed, in SLE anti-
SSA/Roandanti-SSB/Laantibodiesseemtoexertaprotective
role from lupus nephritis [ ].ishypothesisrequiresfur-
ther investigations but could translate into other interesting
ndings in SLE as well.
However, the biggest eort was made to understand
the clinical implications of antibodies found in the sera of
patients aected by SLE. Indeed, the diagnostic and prognos-
ticvaluesofsuchantibodiesarewellknownandnolessthan
two of the American College of Rheumatology (ACR) criteria
for SLE [] regard immunological abnormalities:
". Immunologic disorder:
. Anti-DNA: antibody to native DNA in abnormal titer
or
. Anti-Sm: presence of antibody to Sm nuclear antigen
or
. Positive nding of antiphospholipid antibodies on:
- An abnormal serum level of IgG or IgM anticar-
diolipin antibodies,
- A positive test result for lupus anticoagulant
using a standard method,
- A false-positive test result for at least months
conrmed by treponema pallidum immobiliza-
tion or uorescent treponemal antibody absorp-
tion test
. Positive antinuclear antibody: An abnormal titer of
antinuclear antibody by immunouorescence or an equiv-
alent assay at any point in time and in the absence of
drugs"
Many authors have recently questioned the validity of
these criteria, for example, Bizzaro et al. demonstrated
through a study of meta analysis that the anti-nucleosome
antibodies (AnuA) test is superior for diagnostics than the
test for anti-dsDNA antibodies [ ]. Furthermore Doria et al.
underline that the test for anti-ribosomal P protein antibodies
has a sensitivity and specicity for the classication of
SLE similar to that of anti-Sm antibodies and that it could
possibly substitute anti-Sm antibodies in the ACR criteria
[ , ].
Furthermore, anti-ribosomal P protein antibodies cor-
relate with the activity of the disease and are associated
with neuropsychiatric manifestations of SLE, while anti-
Sm antibodies are frequently static over the disease course
and it is dicult to link them with clinical manifestations.
Nevertheless, the Systemic Lupus International Collaborating
Clinics (SLICC) group recently revised and validated the
ACR SLE classication criteria, maintaining and further
emphasizing the same immunological criteria [ ]. Indeed,
according to the SLICC rules, patients must satisfy at least
criteria, including at least one immunologic criterion, or
the patient must have biopsy-proven lupus nephritis in the
presence of antinuclear antibodies or anti-double stranded
DNA antibodies.
ANAs can be useful to identify particular subsets of
LE: Anti-dsDNA is associated with renal involvement, anti-
Ro/SSA antibodies with photosensitive rash especially sub-
acutelupuserythematosus(SCLE)aswellaswithserositis
and haematological manifestations, anti-P ribosomal protein
with neuropsychiatric disorders, and anti-RNP with arthritis,
Raynaud's, and puy ngers. In this regard, another inter-
estingpointofviewisgivenbyShivastavaandKhanna[ ],
who propose the cluster theory: according to which distinct
autoantibody clustering correlates to particular clinical syn-
dromes. Cluster (anti-Sm and anti-RNP) is characterized by
the lowest incidence of proteinuria, anaemia, lymphopenia,
and thrombocythemia. Cluster (anti-dsDNA, anti-Ro and
anti-L a) is associated with a higher rate of nephritic syndrome
and leukopenia. Cluster (anti-ds-DNA, LAC and aCL) is
expectedly associated with thrombotic events [ ]. Moreover,
Ching et al. [ ] studied the serological proles of SLE
patients, nding that most of them segregated into one of two
distinct clusters dened by autoantibodies against Sm/anti-
RNP or Ro/La autoantigens. e Sm/RNP cluster was asso-
ciatedwithahigherprevalenceofserositisincomparisonto
the Ro/La cluster.
2. Techniques
ANAscanbedetectedbyvariousassays:indirectimmunou-
orescence (IIF) using cultured cells as substrates, enzyme-
linked immunosorbent assay (ELISA), and farr radioim-
munoassay (RIA).
IIF and ELISA are most popular in routine work. ELISA
is more sensitive but less specic while IIF is sensitive,
reproducible, and easy to perform. ELISA is preferable when
the exact titration of ANAs is needed in the follow-up of SLE.
Lately, multiplexed ELISA assays have been used for
ANAs titration and these new sophisticated techniques are
able to detect simultaneously multiple autoantibodies from
a single sample. Until now, various studies report overall
agreement between the detection of lupus autoantibodies by
conventional ELISA and by multiplexed ELISA assays [ –
].
Autoimmune Diseases
F : IIF on Hep cells: homogeneous pattern. Dilution : .
Monolayer of cultured cells, particularly HEp (a human
laryngeal carcinoma cell line), is now considered the gold
standard for IIF. In cultured cells used for IIF, the antigens are
in the native location and form, undenatured or minimally
denatured, and the nuclei and nucleoli are clearly visible in
dividing cells.
About dierent uoroscopic patterns have been
described in IIF, related to dierent antibody specicities.
e most common are homogeneous, peripheral or ring,
speckled, nucleolar, pleomorphic speckled, nuclear dots, and
nuclear membrane. Generally, the homogenous pattern is
linked to SLE (Figure ). ANA pattern has some correlation
with clinical subsets, such as a shrunken peripheral pattern
with renal disease, a ne particulate pattern in SCLE, and
a homogeneous pattern with anti-histone antibodies [ ].
However, the homogenous pattern can be found in many
other autoimmune diseases and, in contrast, various ANA
patterns may coexist in the same disease. For these reasons,
more specic tests, such as the anti-dsDNA test or anti-ENA
testarenecessaryforaprecisediagnosis,accordingtothe
well-known "cascade testing" as suggested by guidelines [ ].
Indeed,itmustbekeptinmindthatANAsmaybefound
not only in autoimmune diseases, but also hepatic diseases,
malignancies, chronic infections, thyroid diseases, and even
in individuals with no medical condition, particularly elderly
people [ , ].
Ippolito et al. [ ] report the results of current serologic
tests for SLE are generally consistent with the historical ones.
However, probably due to their better sensitivity, current
serological tests yield a certain percentage of additional
positives. Further, due to a lower sensitivity in the past tests
for C and C detected more frequently the depletion of these
factors.
3. Anti-DNA Antibodies
Anti-DNA antibodies constitute a subgroup of antinuclear
antibodies that bind to either single-stranded or double-
stranded DNA [ ]. Both subtypes of DNA-binding antibod-
ies may be found in SLE. Nonetheless, while some authors
highlighted a possible role of anti-ssDNA antibodies in
thediagnosisandfollow-upofSLE,especiallywhenanti-
dsDNA antibodies were negative [ , ], others doubted the
specicity and utility of this test [ – ]. Instead, because of
their high specicity, anti-dsDNA antibodies are universally
used as a diagnostic criterion for SLE (–% of patients
are positive for such antibodies) [ ] and for monitoring the
clinical course of the patient [ ] (every weeks, for example),
especially in the presence of an immunosuppressive treat-
ment that reduces their production. IIF on Crithidia luciliae
(Figure ), RIA, and ELISA is the most commonly used assays
to detect anti-dsDNA antibodies. IIF-based Crithidia assay is
probably the most specic technique, but ELISA is the most
practical and clinically relevant method. In IIF anti-dsDNA
antibodies correlate with a shrunken peripheral ANA pattern
[ ]. It is generally accepted that anti-dsDNA antibodies, in
particular of the IgG isotype, have an important pathogenetic
role in SLE. A clear-cut relationship exists, for example,
between anti-dsDNA antibodies (RA antibody) [ ]and
diseaseactivityinnephritis[ ]. Anti-DNA-DNA immune
complexes can deposit in the mesangial matrix and their sub-
sequent complement activation leads to inammation and
mesangial nephritis. Moreover, anti-dsDNA antibodies also
contribute to the end-stage lupus nephritis by directly bind-
ing exposed chromatine fragments in glomerular basement
membrane [ ]. On the other hand, IgM-class anti-dsDNA
antibodies seem to have a protective role for nephropathy
[ , ]. Furthermore De Giorgio et al. demonstrated that a
subset of anti-DNA antibodies cross-reacts with N-methyl-
D-aspartate receptors (NMDAR), and through an excitotoxic
mechanism, could induce neuronal apoptosis. Anti-NMDAR
antibodies are present in % of lupus patients and some
reports have supported the correlationbetween such antibod-
ies and the presence of neuropsychiatric lupus [ ,, ],
whileothershavenot[ ]. More recently, Franchin et al. have
demonstrated that anti-NMDAR antibodies also bind Cq;
therefore, they hypothesized that this subset of anti-DNA
antibodies contributes in lupus pathogenesis through direct
targeting of Cq on glomeruli and also through removal of
soluble Cq thereby limiting the ability of Cq to suppressor
of immune activation [ ].
4. Anti-Sm Antibodies
Sm antigen consists of at least proteins: B (kDa), B
( kDa), D ( kDa), and E ( kDa). Anti-Sm antibodies are
a highly specic marker for SLE and Anti-Sm reactivity is
not described in other diseases. eir sensitivity is however
low. In fact, anti-Sm antibodies are detectable only in % of
SLE white patients, but –% in black and Asian people.
Clinical correlations of these autoantibodies remain unclear
[ ] and generally show persistent expression over time [ ].
In some studies anti-Sm titers were found to uctuate with
disease activity and treatment [ ],butitisunclearwhether
serial monitoring predicts relapse [ ].
5. Anti-Nucleosome Antibodies
e antigen consists of pairs of core histones: HA, HB,
H, and H, forming the histone octamer around which
pairs of basis of DNA are wound twice, with H bound
Autoimmune Diseases
F : IIF on HEp cells: speckeld and nuclear and nucleolar
staining (anti-SSA/Ro antibodies). Dilution : .
on the outside. Anti-nucleosomes antibodies (ANuA) react
exclusively to nucleosomes and not to individual histones or
native non-protein-complexed DNA [ ].
Although anti-nucleosome antibodies can be seen in IIF
as homogeneous pattern (Figure ), only ELISA detects them.
ey represent the rst serological marker of SLE
described and, at present, nucleosomes are considered a
majorautoantigeninSLEinwhichtheyarepositiveinabout
% of patients and probably play an important pathogenetic
role [ ]. ere is major evidence that nucleosome antibodies
play an important role in the pathogenesis of SLE, being the
rst ones to appear in murine lupus models before the onset
of any other autoantibodies, which are only later produced
byBcells,stimulatedbynucleosome-specicTcellsthrough
epitope spreading [ ]. In glomerulonephritis, nucleosomes
facilitate binding of autoantibodies to glomerular basement
membranes with an increased permeability and inamma-
tory response [ , ].
According to Bizzaro's meta-analysis ANuA test appears
to have an adequate level of diagnostic accuracy for SLE, with
equal specicity, but higher sensitivity, positive likelihood
ratio, and diagnostic odds ratio than anti-dsDNA antibodies
test [ ]. Indeed, they could be one of the most sensitive
markers in the diagnosis of SLE, especially in anti-ds-
DNA-negative patients [ ]. Furthermore, there is a strong
correlation between the level of anti-nucleosome antibodies
andlupusdiseaseseverity[ , , ]. ANuAs are probably
better to predict ares in quiescent lupus [ ].
6. Anti-Histone Antibodies
e target antigens are major classes of histones (H,
HA, HB, H, and H), which organize and constrain the
topology of DNA.
ELISA is the only reliable method for detection of anti-
histone antibodies. It is important to use IgG-specic anti-
bodies and not IgM that are not specically related to the
disease. Using IIF on standard substrates anti-histone anti-
bodies produces a homogeneous, chromosome-positive
staining of the nucleus.
ese autoantibodies are characteristic of particular sub-
set of SLE. In fact, anti-HA-Hb antibodies are a sensitive
test in drug-induced SLE. About % of patients with SLE
induced by procainamide [ ]and%ofpatientswithSLE
induced by penicillamine, isoniazid [ ], and methyldopa
have anti-histone antibodies. Nonetheless, they are also
present in idiopathic SLE (% of patients with SLE [ ]),
in rheumatoid arthritis, Felty's syndrome, Sj¨
ogren's syndrome
(SS), systemic sclerosis (SSc) [ ], primary biliary cirrhosis,
infectious diseases (including HIV infection), and even neu-
rological disorders such as Alzheimer's disease and dementia.
In our experience, anti-histone antibodies are found in %
of SLE patients and in % of SSc patients [ ]. However,
because of their low specicity these anti-histone antibodies
albeit more prevalent, are not pathognomonic of drug-induce
SLE [ ]. is apparent paradox might be explained by the
fact that the metabolites of oending drugs probably have the
capacity to disrupt nonspecically central immune tolerance
to chromatin [ ]. From a pathogenetic point of view, the
histone-anti-histone antibody system might play a role in the
perpetuation of murine lupus nephritis [ ]andrecentlySui
et al. demonstrate in their study a strong association between
simultaneous positivity to anti-DNA, anti-nucleosome, and
anti-histone antibodies and renal disease activities, especially
in proliferative glomerulonephritis [ ].
7. Anti-SSA/Ro Antibodies
SSA/Ro antigen is a ribonucleoprotein containing small
uridine-rich nucleic acids known as hY, hY, hY, and
hY (hY is the abbreviation of human cytoplasmic). SSA/Ro
antigenconsistsofatleastofproteins:,,,andkDa,
respectively, with the best known of them being the and
kDa proteins [ ].
e most sensitive and specic method for detection of
anti-SSA/Ro antibodies is ELISA. Using tumoral cell lines
transfected with SSA/Ro antigen (HEp ) as a substrate,
IIF is useful too, showing a typical speckled nuclear and
nucleolar staining (Figure ).
Anti-SSA/Ro antibodies might have a pathogenetic role
intheinitiationoftissuedamageespeciallyinphotosensitive
SLE, for ultraviolet radiation has been shown to induce de
novo synthesis and the expression on the cell surface of
SSA/Ro polypeptides in keratinocytes [ , ].
Since the s, it was known that anti-SSA/Ro and anti-
SSB/La antibodies can cross the maternal placenta and deter-
mine neonatal lupus erythematosus (NLE). Indeed, anti-
SSA/Ro as well as also anti-SSB/La antibodies bind to fetal
heart conduction tissue and inhibit cardiac repolarization
[ ], determining isolated complete atrioventricular block
(CHB). Other frequently observed manifestations of NLE
are cutaneous rash, haematological disorders (thrombocy-
topenia, anemia, and leukopenia), and liver dysfunction [ ],
all of which tend to resolve within the time of clearance of
maternal antibodies from the infant's circulation.
In a recent paper, it was reported that newborns from
mothers with high to moderate titers of anti-SSA/Ro antibod-
ies are more likely to develop cardiac manifestations of NLE,
independently from the anti-SSB/La titers, while infants with
prenatal exposure to high titers of anti-SSB/La antibodies
were most likely to present non-cardiac manifestations [ ].
Autoimmune Diseases
Anti-SSA/Ro antibodies can be detected in –% of
patients with SS, in –% of patients in particular in SCLE
and NLE (–%) and with a lower frequency also in dis-
coid LE (–%). Antibodies to the kDa subunit are
more specic for SS while antibodies to the kDa subunit
are more frequent in SLE patients. Anti-Ro and Anti-La
antibodies are found earlier than other SLE-related autoan-
tibodies and are present on average . years before the
the diagnosis of SLE [ ]. A close association between anti-
SSA/Ro antibodies and late onset of SLE (average age of
) was suggested [ ]. Anti-SSA/Ro antibodies correlate
with photosensitivity, SCLE, cutaneous vasculitis (palpable
purpura), and haematological disorders (anemia, leukopenia,
and thrombocytopenia) [ , – ].
ere are discordant data regarding the association
between anti-SSA/Ro titers and the disease activity, but it
seems that anti-SSA/Ro antibody levels tend to decline when
patients are treated with cytotoxic drugs [ – ].
Recently, greater attention is being paid toward distin-
guishing the two subtypes of anti-SSA/Ro: anti-SSA/Ro
and anti-Ro/TRIM. A recent retrospective study con-
ducted by Menendez et al. supports their routine distinction
in clinical practice, since the two subtypes show dierent
associations with dierent clinical subtypes of SLE. Indeed,
anti-SSA/Ro are more frequently reported in association
with SLE and CLE. Nevertheless, the pattern with both anti-
SSA/Ro and anti-Ro/TRIM is more frequent in SCLE
and anti-Ro/TRIM is more strongly associated with CHB
[ ]. In particular, the antibodies that seem to be strictly
linked to CHB are directed against peptide aa – of
subunit kDa of Ro/SSA antigen [ ].
8. Anti-SSB/La Antibodies
e SSB/La particle is a – kDa nuclear phosphoprotein
composed of distinct regions of and kDa [ ]. e
larger domain contains a RNA binding site that binds RNA
polymerase III transcripts. Although anti-SSB/La antibodies
were originally detected by immunodiusion and counter-
immunoelectrophoresis, they are now commonly detected by
ELISA and immunoblotting.
Even though there is no direct evidence of a pathogenetic
role of anti-SSB/La antibodies in SS and SLE, their presence in
maternal blood is strongly associated with NLE and congen-
ital heart block. In fact, both SSB/La and SSA/Ro antibodies
bind to the surface of the bres of the heart suggesting that
the maternal anti-SSB/La and anti-SSA/Ro antibodies bind
to the surface of cardiac muscle cells and damage them. Anti-
SSB/La antibodies are the serological marker of SS [ ]: if
detected by ELISA, anti-SSB/La antibodies are present in %
of patients with primary SS and % with secondary SS. In
SLE, anti-SSB/La antibodies are instead present only in about
% of patients with lower prevalence of renal disease. About
% of patients with SCLE have anti-SSB/La antibodies.
9. Anti-Ribosomal P Antibodies
Ribosomes are complex macromolecular structures incorpo-
rating both protein and ribonucleic acid (RNA) elements.
Mammalian ribosomes are formed by the S and S
subunit. e S subunit is a ribonucleoprotein complex con-
taining a single S species of RNA and dierent basic pro-
teins. e S subunit incorporates distinct species of RNA,
dierent basic proteins, and phosphoproteins named P,
P, and P of , and kDa, respectively, that are the most
important antigen targets of anti-ribosomal antibodies [ ].
e specicity of autoantibodies directed against riboso-
mal components is evaluated by immunoblotting, but their
presence is already suggested in IIF by a cytoplasmatic
pattern. In the routine work, however, they are usually
detected by ELISA. In comparative studies immunoblotting
and ELISA seem to give the same diagnostic accuracy [ ].
More recently, the international multicentre evaluation of the
clinical accuracy of a new ELISA based on recombinant P
polypeptides demonstrated that a combination of all three P
proteins resembling the native heterocomplex P (P/P)2 as
antigengivesthebestaccuracy[ ].
Anti-ribosomal P antibodies seem to have an intrigu-
ing pathogenetic potential that needs further investigations.
Indeed, anti-ribosomal P antibodies may exert dierent
cellular eects by binding to the surface of T cells, monocytes,
and endothelial cells [ ].
ey are able to penetrate into living cells by binding
a cell-surface kDa protein, which is the corresponding
surface version of P ribosomal protein. In this way, they can
causecellulardysfunctionandtissuedamagebyinhibiting
protein synthesis, inducing apoptosis or proinammatory
cytokine production [ ]. More recently, two independent
groups elucidated the neuropathogenic potential of anti-
ribosamal P antibodies [ , ]. Moreover, Caponi et
al. demonstrated that anti-ribosomal P antibodies in some
cases can cross react with cardiolipin, ssDNA, dsDNA, and
also nucleosomes. Such data indicate a partial overlapping
of anti-ribosmal P antibodies with the other autoantibody
populations detected frequently in SLE. For this reason anti-
ribosomal P might have a similar pathogenetic role, for
instance, in NPSLE [].
e autoimmune response to ribosomal components is
quite specic for SLE. Anti-ribosomal P antibodies occur in
–% of Caucasian SLE patients and in more than % of
Asian patients [ ].
Since the rst prospective study in by Bonfa et al.
[ ] reporting a strong association between anti-ribosomal P
antibodies and lupus psychosis, many other studies tried to
conrm the utility of such antibodies in predicting NPSLE.
However, the results were contrasting [ , ]. Anyhow,
many studies report associations with psychosis and espe-
cially depression.
10. Anti-Phospholipid Antibodies
e study of anti-phospholipid antibodies (aPL) antibodies
beganinwhenWassermanintroducedhisserological
test for syphilis [ ].In,theactivecomponentwas
foundtobeaphospholipid,whichwascalledcardiolipin
[ ]. Aer the s, it became clear that people with positive
Wasserman-test did not necessarily have syphilis but that
they may have instead an autoimmune disorder, including
Autoimmune Diseases
SLE [ ]. e term lupus anticoagulant (LAC) rst used
in should be abandoned because LA can be found in
patients without SLE and it is associated with thrombosis
and not with bleeding [ ].
Anti-PL antibodies recognize a number of anionic neg-
atively charged phospholipids, including cardiolipin (CL),
LAC, phosphatidylserine (PS), phosphatidylinositol (PI),
phosphatidylglycerol, and phosphatidic acid (PA). Neu-
trally charged autoantigen targets include phosphatidyl
ethanolamine, phosphatidyl choline, platelet activating factor
and sphingomyelin. ese antibodies are usually detected
with radioimmunoassay and ELISA. CL remains the most
commonly used antigen for detecting anti-PL antibodies with
ELISA. It is now clear, however, that the optimal binding of
anti-PL antibodies depends on cofactors; the best known of
them is termed Beta-Glycoprotein I (BetaGP), that is, a
kDa B globulin involved in the regulation of blood coag-
ulation [ ]. ELISA testing for BetaGP is also available [ ].
As mentioned before, anti-PL antibodies are not conned
to SLE patients but can be found in other autoimmune
diseases, infections, malignant, and drug-induced disorders
as well as in some apparently healthy individuals. In addition,
anti-PL antibodies are positive in –% of SLE patients,
but only / of them develop clinical features of anti-PL
syndrome, namely, venous thrombosis, arterial thrombosis,
recurrent pregnancy loss, thrombocytopenia and haemolytic
anaemia, livedo reticularis, and skin ulcers [ ]. Furthermore,
aPL antibodies are involved in cerebral vascular disease and
arealsoimpliedinthepathogenesisoffocaldamagein
NPSLE. In particular, anti-betaGPI antibodies are the most
thrombogenic and may exert a pathogenetic potential either
as a strong procoagulant factor in the cerebral circulation or
by directly interacting with neuronal tissue [ ].
11. Anti-C1q Antibodies
Cq is a cationic glycoprotein of – kDa, which binds to
the Fc portions of immunoglobulins in immune complexes
to initiate complement activation via the classical pathway
[ ]. Cq is produced by macrophages, monocytes, dendritic
cells, broblasts, and epithelial cells and acts like a binding
molecule between debris from cellular apoptosis (apoptotic
blebs) and macrophages. erefore, anti-Cq antibody devel-
opment seems to be related to a deciency in apoptotic cell
clearance, as suggested by the fact that such antibodies from
SLE patients specically bind to Cq on apoptotic cells [ ].
Anti-Cq antibodies are commonly detected by ELISA.
From a pathogenic point of view anti-Cq antibodies proba-
bly amplify glomerular injury but only when Cq has already
been brought to the site by other types of glomerular-reactive
autoantibodies [ ]. Furthermore, Hegazy et al. recently
reported in their study a strong correlation between anti-Cq
antibodies and cutaneous lupus and hypothesised a potential
pathogenetic role in such context [ ].
ey are found in SLE with a prevalence ranging from %
to %, especially in patients with nephritis [ ]. Moroni sug-
geststhattheelevationoftheirtitersmaypredictrenalares
even better than anti-dsDNA antibody levels [ ]. Elevated
titres of anti-Cq antibodies are usually associated with the
F : IIF on Hep cells: speckled pattern (anti-RNP antibodies).
Dilution : .
proliferative forms of lupus nephritis and with subendothelial
deposits of immune complexes. ey are therefore a useful
marker for assessing both disease activity and progression of
the renal disease [ ]. Anti-Cq antibodies can be found also
in other autoimmune diseases such as hypocomplementemic
urticarial vasculitis syndrome, rheumatoid arthritis, Felty's
syndrome, rheumatoid vasculitis, Sj¨
ogren's syndrome, mem-
branoproliferative glomerulonephritis (MPGN), and IgA
nephropathy [ , ].
12. Anti-RNP Antibodies
Anti-RNP antibodies are directed to at least proteins
of kDa (U), kDa (protein A), and kDa (protein
C), respectively. In IIF anti-RNP antibodies produce a ne
speckled staining (Figure ). Anti-Usmall nuclear (sn) RNP
antibodies are considered pathognomonic for Sharp's syn-
drome (mixed connective tissue disease or MCTD), but
they can be found in –% of patients with SLE as well
[ ]. eir presence is associated with HLA DR and their
prevalence is higher in African American patients [ ]. Other
diseases in which anti-UsnRNP activity is described include
rheumatoid arthritis, polymyositis, SSc, and Sj¨
ogren's syn-
drome (SS). Data from recent experimental studies promote
the hypothesis that UsnRNP antibodies participate in both
innate and adaptive immune responses, implicating them in
the pathogenesis of connective tissue disease [ ]. According
to some authors anti-RNP antibodies are more prevalent in
patients with Raynaud's phenomenon and are associated with
milder renal involvement [ ]. Although, ultimately anti-U
RNP antibodies do not reect the disease activity and their
utility in monitoring the latter remains unclear.
13. Anti-Proliferating Cell Nuclear Antigen
(PCNA) Antibodies
Anti-PCNA antibodies can be detected by using IIF on
cultured cells in which they show a characteristic nuclear
speckled pattern of varying intensity (Figure ). ELISA kits
arealsoavailable.PCNAisanauxiliaryproteinforDNA
polymerase delta. PCNA expression increases proportionally
to DNA synthesis and/or cell growth, beginning in late
G, increasing in S, and decreasing in G cellular phases.
Autoimmune Diseases
F : IIF on Hep cells: speckled pattern of varying intensity
(anti-PCNA antibodies). Diluition : .
Anti-PCNA antibodies are present in –% of SLE patients
especially those with arthritis and hypocomplementemia
[ ]. Aer treatment with steroids or cytotoxic drugs, anti-
PCNA antibodies become undetectable.
14. Serology of SLE in Overlap Syndromes
SLE can be associated with other autoimmune diseases such
as Sj¨
ogren's syndrome (SS), systemic sclerosis (SSc), rheuma-
toid arthritis (RA), dermatomyositis (DM)/polymyositis
(PM), and determining overlap syndromes (OSs). OSs share
clinical and immunological features of two or more distinct
autoimmune diseases and might also have their own peculiar
features. From a serological point of view OSs can be asso-
ciated with a specic antibody prole (MCTD and SLE/SS)
or not associated with a specic antibody prole (rhupus
syndrome, SLE/SSc). MCTD has mixed features of SLE,
SSc, DM/PM, and RA, in which anti-UsnRNP antibodies
are the specic antibodies of the disease (see above). Anti-
Ro/SS-A, anti-ssDNA, anti-Sm, anti-dsDNA [ ], and anti-
PL antibodies [ ] have also been detected; nevertheless,
they are not specic of MCTD. Recently, autoantibodies to
angiotensin-converting enzyme (ACE) [ ]werealso
reported in MCTD. SLE/SS patients have a higher frequency
of SS-related immunological markers, such as rheuma-
toid factor (RF), polyclonal hypergammaglobulinemia, anti-
Ro/SSA, and anti-La/SSB, while SLE-related antibodies are
less frequent [ ]. Anti-La/SSB antibodies are considered
the serological markers of this OS. Most authors dene
rhupus syndrome as a condition characterized by signs and
symptoms of both SLE and RA [ , ]. In patients aected
by such OS no specic antibody is identiable and specic
autoantibodies for SLE (anti-dsDNA and anti-Sm) and RA
(anti-citrullinated peptides ACPA) coexist [ ]. SLE/SSc
overlap is a rare condition, in which a specic serological
marker has not been identied yet, but a high incidence
of anti-dsDNA and anti-Scl antibodies has been reported
[].
15. Conclusions
e comprehension of pathogenetic mechanisms is the start-
ingpointforthedevelopmentofnewandbetterlaboratory
tests, with various clinical implications. For example, the dis-
covery of the cross-reactivity of certain types of anti-dsDNA
antibodies with the NMDA receptor helped to comprehend
thepathogenesisofNPSLE,butthedetectionofsuchantibod-
ies in patients' sera could also be a potential predictive marker
of the risk of developing NP disorders in SLE. Furthermore,
distinguishing between the two dierent subtypes of anti-
SSA/Ro antibodies might have interesting clinical implica-
tions. A better knowledge of the specicities of the antibodies
might be a useful tool to subclassify patients with lupus and
to predict which clinical manifestations they might develop.
Detecting simultaneously a battery of various antibodies with
multiplexed ELISA could be helpful for this purpose.
For the diagnosis of lupus certainly ds-DNA antibodies
are an excellent biomarker, but we believe that perhaps
ANuAs might be a better one, in accordance with Bizzaro's
meta analysis, and considering that from a pathogenetic point
of view these autoantibodies are the rst ones to appear.
e role played by autoantibodies in the pathogenesis of
lupus is yet to be revealed in many respects and the strive to
ndnewandmorevalidbiomarkersforabettermanagement
of the disease is constant, being lupus such a complex disease.
erefore, we believe there is still room for improvement as
far as lupus serology is concerned.
Conflict of Interests
e authors declare that there is no conict of interests
regarding the publication of this paper.
References
[] Y. Sherer, A. Gorstein, M. J. Fritzler, and Y. Shoenfeld, "Autoanti-
body explosion in systemic lupus erythematosus: more than
dierent antibodies found in SLE patients," S eminars in Arthritis
and Rheumatism ,vol.,no.,pp.–,.
[] M. Hargraves, H. Richmond, and R. Morton, "Presentation of
twobonemarrowcomponents,thetartcellandtheLEcell,"
Mayo Clinic Proceedings ,vol.,pp.–,.
[] R.Ceppellini,E.Polli,andF.Celada,"ADNA-reactingfactorin
serum of a patient with lupus erythematosus diusus," Proceed-
ings of the Society for Experimental Biology and Medicine,vol.
,no.,pp.–,.
[] E.M.TanandH.G.Kunkel,"Characteristicsofasolublenuclear
antigen precipitating with sera of patients with systemic lupus
erythematosus," JournalofImmunology ,vol.,no.,pp.–
, .
[] O. P. Rekvig, C. Putterman, C. Casu et al., "Autoantibodies in
lupus: culprits or passive bystanders?" Autoimmunity Reviews,
vol. , no. , pp. –, .
[] R. Gualtierotti, M. Biggioggero, A. E. Penatti, and P. L. Meroni,
"Updating on the pathogenesis of systemic lupus erythemato-
sus," Autoimmunity Reviews ,vol.,no.,pp.–,.
[] B.Diamond,O.Bloom,Y.AlAbed,C.Kowal,P.T.Huerta,and
B. T. Volpe, "Moving towards a cure: blocking pathogenic anti-
bodies in systemic lupus erythematosus," JournalofInternal
Medicine,vol.,no.,pp.–,.
[] B. Wittemann, G. Neuer, H. Michels, H. Truckenbrodt, and F.
A. Bautz, "Autoantibodies to nonhistone chromosomal proteins
Autoimmune Diseases
HMG- and HMG- in sera of patients with juvenile rheuma-
toid arthritis," Arthritis & Rheumatism ,vol.,no.,pp.–
, .
[] D.A.Abdulahad,J.Westra,J.Bijzet,P.C.Limburg,C.G.M.
Kallenberg, and M. Bijl, "High mobility group box (HMGB)
and anti-HMGB antibodies and their relation to disease char-
acteristics in systemic lupus erythematosus," Arthritis Research
&erapy , vol. , no. , article R, .
[] H. Schierbeck, P. Lundb¨
ack, K. Palmblad et al., "Monoclonal
anti-HMGB (high mobility group box chromosomal protein
) antibody protection in two experimental arthritis models,"
Molecular Medicine, vol. , no. -, pp. –, .
[] D. S. Pisetsky, "Antinuclear antibodies in rheumatic disease: a
proposal for a function-based classication," Scandinavian Jour-
nal of Immunology,vol.,no.,pp.–,.
[] A.Fauci,D.Kasper,D.Longo,E.Braunwald,S.Hauser,andJ.
L. Jameson, Harrison's Principles of Internal Medicine ,McGraw-
Hill, th edition, .
[] M. C. Hochberg, "Updating the American College of Rheuma-
tology revised criteria for the classication of systemic lupus
erythematosus," Arthritis & Rheumatism ,vol.,no.,p.,
.
[] N.Bizzaro,D.Villalta,D.Giavarina,andR.Tozzoli,"Areanti-
nucleosome antibodies a better diagnostic marker than anti-
dsDNA antibodies for systemic lupus erythematosus? A syste-
maticreviewandastudyofmetanalysis,"Autoimmunity Re-
views,vol.,no.,pp.–,.
[] A. Ghirardello, L. Caponi, F. Franceschini et al., "Diagnostic
tests for antiribosomal P protein antibodies: a comparative eva-
luation of immunoblotting and ELISA assays," e Journal of
Autoimmunity,vol.,no.-,pp.–,.
[] A. Doria, M. Zen, M. Canova et al., "SLE diagnosis and treat-
ment: when early is early," Autoimmunity Reviews ,vol.,no.,
pp.–,.
[] J. G. Hanly, M. B. Urowitz, F. Siannis et al., "Derivation and
validation of the Systemic Lupus International Collaborating
Clinics classication criteria for systemic lupus erythematosus,"
Arthritis & Rheumatism,vol.,no.,pp.–,.
[] A. Shivastava and D. Khanna, "Autoantibodies in systemic lupus
erythematosus: revisited," Indian Journal of Rheumatology ,vol.
, no. , pp. –, .
[] C. H. To and M. Petri, "Is antibody clustering predictive of clin-
ical subsets and damage in systemic lupus erythematosus?"
Arthritis & Rheumatism, vol. , no. , pp. –, .
[] K. H. Ching, P. D. Burbelo, C. Tipton et al., "Two major auto-
antibody clusters in systemic lupus erythematosus," PLoS ONE ,
vol.,no.,ArticleIDe,.
[] S. D. Marks and K. Tullus, "Autoantibodies in systemic lupus
erythematosus," Pediatric Nephrology,vol.,no.,pp.–
, .
[] A. S. Wiik, M. Høier-Madsen, J. Forslid, P. Charles, and J. Mey-
rowitsch, "Antinuclear antibodies: a contemporary nomencla-
ture using HEp- cells," e Journal of Autoimmunity ,vol.,
no. , pp. –, .
[] Y. Arinuma, T. Yanagida, and S. Hirohata, "Association of cere-
brospinal uid anti-NR glutamate receptor antibodies with
diuse neuropsychiatric systemic lupus erythematosus," Arthri-
tis & Rheumatism,vol.,no.,pp.–,.
[] K. E. Hansen, J. Arnason, and A. J. Bridges, "Autoantibodies and
common viral illnesses," Seminars in Arthritis and Rheumatism,
vol.,no.,pp.–,.
[] D. A. Isenberg, J. J. Manson, M. R. Ehrenstein, and A. Rahman,
"Fiy years of anti-ds DNA antibodies: are we approaching
journey's end?" Rheumatology,vol.,no.,pp.–,
.
[] R.Maya,M.E.Gershwin,andY.Shoenfeld,"HepatitisBvirus
(HBV) and autoimmune disease," Clinical Reviews in Allergy
and Immunology,vol.,no.,pp.–,.
[] G. W. Zieve and P. R. Khusial, "e anti-Sm immune response
in autoimmunity and cell biology," Autoimmunity Reviews ,vol.
, no. , pp. –, .
[] K.D.PaganaandT.J.Pagana,Mosby's Diagnostic and Labora-
tory Test Reference, th edition, .
[] A. Bruns, S. Bl¨
ass, G. Hausdorf, G. R. Burmester, and F. Hiepe,
"Nucleosomes are major T and B cell autoantigens in systemic
lupus erythematosus," Arthritis & Rheumatism,vol.,no.,
pp. –, .
[]P.Quattrocchi,A.Barrile,D.Bonannoetal.,"eroleof
anti-nucleosome antibodies in systemic lupus erythematosus.
Results of a study of patients with systemic lupus erythematosus
and other connective tissue diseases," Reumatismo ,vol.,no.
, pp. –, .
[] R. L. Rubin, R. W. Burlingame, J. E. Arnott, M. C. Totoritis, E. M.
McNally,andA.D.Johnson,"IgGbutnototherclassesofanti-
[(HA-HB)-DNA] is an early sign of procainamide-induced
lupus," Journal of Immunology,vol.,no.,pp.–,
.
[] M. Salazar-Paramo, R. L. Rubin, and I. Garcia-De La Torre,
"Systemic lupus erythematosus induced by isoniazid," Annals of
the Rheumatic Diseases,vol.,no.,pp.–,.
[] C. Eriksson, H. Kokkonen, M. Johansson, G. Hallmans, G.
Wade ll , and S . Ra ntap¨
a¨
a-Dahlqvist, "Autoantibodies predate the
onset of systemic lupus erythematosus in northern Sweden,"
Arthritis Research & erapy, vol. , no. , article R, .
[] E.K.L.Chan,J.C.Hamel,J.P.Buyon,andE.M.Tan,"Molecular
denition and sequence motifs of the -kD component of
human SS-A/Ro autoantigen," e Journal of Clinical Investiga-
tion,vol.,no.,pp.–,.
[] R. Yoshimi, A. Ueda, K. Ozato, and Y. Ishigatsubo, "Clinical
and pathological roles of Ro/SSA autoantibody system," Clinical
and Developmental Immunology,vol.,ArticleID,
pages, .
[]T.L.Rivera,P.M.Izmirly,B.K.Birnbaumetal.,"Disease
progression in mothers of children enrolled in the Research
Registry for Neonatal Lupus," Annals of the Rheumatic Diseases ,
vol. , no. , pp. –, .
[] A. Ghirardello, A. Doria, S. Zampieri, P. F. Gambari, and S.
Todesco, "Autoantibodies to ribosomal P proteins in systemic
lupus erythematosus," Israel Medical Association Journal ,vol.,
no. , pp. –, .
[] J. G. Hanly, M. B. Urowitz, F. Siannis et al., "Autoantibodies
and neuropsychiatric events at the time of systemic lupus ery-
thematosus diagnosis: results from an international inception
cohort study," Arthritis & Rheumatism ,vol.,no.,pp.–
, .
[] P. Chu, K. Pendry, and T. E. Blecher, "Detection of lupus anti-
coagulant in patients attending an anticoagulation clinic,"
British Medical Journal , vol. , no. , p. , .
[]A.Hegazy,A.F.Barakat,M.A.E.Gayyar,andL.F.Arafa,
"Prevalence and clinical signicance of anti-Cq antibodies in
cutaneous and systemic lupus erythematosus," e Egyptian
JournalofMedicalHumanGenetics ,vol.,pp.–,.
Autoimmune Diseases
[] M. H. Wener, M. Mannik, M. M. Schwartz, and E. J. Lewis,
"Relationship between renal pathology and the size of cir-
culating immune complexes in patients with systemic lupus
erythematosus," Medicine ,vol.,no.,pp.–,.
[] G. C. Williamson, J. Pennebaker, and J. A. Boyle, "Clinical cha-
racteristics of patients with rheumatic disorders who possess
antibodies against ribonucleoprotein particles," Arthritis &
Rheumatology,vol.,no.,pp.–,.
[] G. C. Williamson, A. Mary, L. M. Snyder, and J. B. Wallach,
"Autoimmune and miscellaneous diseases," in Wa ll ac h's In te r-
pretationofDiagnosticTests ,p.,WoltersKluwer,Lippincott
Williams & Wilkins, Philadelphia, Pa, USA, .
[] J.Wenzel,R.Bauer,T.Bieber,andI.B
¨
ohm, "Autoantibodies in
patients with lupus erythematosus: spectrum and frequencies,"
Dermatology,vol.,no.,pp.–,.
[] T.-C. Hsu, G. J. Tsay, T.-Y. Chen, Y.-C. Liu, and B.-S. Tzang,
"Anti-PCNA autoantibodies preferentially recognize C-termi-
nal of PCNA in patients with chronic hepatitis B virus infec-
tion," Clinical & Experimental Immunology ,vol.,no.,pp.
–, .
[] J.G.Hanly,L.Su,V.Farewell,andM.J.Fritzler,"Comparison
between multiplex assays for autoantibody detection in sys-
temic lupus erythematosus," JournalofImmunologicalMethods ,
vol. , no. -, pp. –, .
[] N. Bardin, S. Desplat-Jego, L. Daniel, N. Jourde Chiche, and M.
Sanmarco, "BioPlexe multiplexed system: simultaneous
detection of anti-dsDNA and anti-chromatin antibodies in
patients with systemic lupus erythematosus," Autoimmunity ,
vol.,no.,pp.–,.
[] J. G. Hanly, K. ompson, G. McCurdy, L. Fougere, C. eriault,
and K. Wilton, "Measurement of autoantibodies using multi-
plex methodology in patients with systemic lupus erythemato-
sus," Journal of Immunological Methods,vol.,no.-,pp.–
, .
[] W. D. James, T. G. Berger, and D. M. Elston, Andrews' Diseases of
the Skin. Clinical Dermatology, Saunders Elsevier, th edition,
.
[] D. H. Solomon, A. J. Kavanaugh, P. H. Schur et al., "Evidence-
based guidelines for the use of immunologic tests: antinuclear
antibody testing," Arthritis & Rheumatism ,vol.,no.,pp.
–, .
[] N. Bizzaro and A. Wiik, "Appropriateness in anti-nuclear
antibody testing: from clinical request to strategic laboratory
practice," Clinical and Experimental Rheumatology,vol.,no.
, pp. –, .
[]E.Bonfa,S.J.Golombek,L.D.Kaufmanetal.,"Association
between lupus psychosis and anti-ribosomal P protein antibod-
ies," e New England Journal of Medicine ,vol.,no.,pp.
–, .
[] A. Ippolito, D. J. Wallace, D. Gladman et al., "Autoantibodies
in systemic lupus erythematosus: comparison of historical and
current assessment of seropositivity," Lupus ,vol.,no.,pp.
–, .
[] B. H. Hahn, "Antibodies to DNA," e New England Journal of
Medicine, vol. , no. , pp. –, .
[] M. Teodorescu, "Clinical value of anti-ssDNA (denatured
DNA) autoantibody test: beauty is in the eyes of the beholder,"
Clinical and Applied Immunology Reviews,vol.,no.,pp.–
, .
[] J. D. Reveille, "Predictive value of autoantibodies for activity of
systemic lupus erythematosus," Lupus ,vol.,no.,pp.–
, .
[] C.-L. Yu, M.-H. Huang, C.-Y. Tsai et al., "e reactivity of sera
from patients with systemic lupus erythematosus to seven dif-
ferent species of single and double stranded deoxyribonucleic
acids," Clinical and Experimental Rheumatology ,vol.,no.,
pp.–,.
[] S. Albani, M. Massa, S. Viola, G. Pellegrini, and A. Martini,
"Antibody reactivity against single stranded DNA of various
species in normal children and in children with diuse connec-
tive tissue diseases," Autoimmunity ,vol.,no.,pp.–,.
[] R. Misra, A. N. Malaviya, R. Kumar, and A. Kumar, "Clinical
relevance of the estimation of antibodies to single stranded
DNA in systemic lupus erythematosus," e Indian Journal of
Medical Research, vol. , pp. –, .
[] D. Koer, V. Agnello, R. Winchester, and H. G. Kunkel, "e
occurrence of single-stranded DNA in the serum of patients
with systemic lupus erythematosus and other diseases," e
Journal of Clinical Investigation,vol.,no.,pp.–,.
[] H. Bootsma, P. Spronk, R. Derksen et al., "Prevention of relapses
in systemic lupus erythematosus," e Lancet ,vol.,no.,
pp.–,.
[] S. Yung and T. M. Chan, "Autoantibodies and resident renal
cells in the pathogenesis of lupus nephritis: getting to know the
unknown," Clinical and Developmental Immunology ,vol.,
Article ID , pages, .
[] Y. Shoenfeld and E. Toubi, "Protective autoantibodies: role in
homeostasis, clinical importance, and therapeutic potential,"
Arthritis & Rheumatism,vol.,no.,pp.–,.
[] T. Witte, "IgM antibodies against dsDNA in SLE," Clinical
Reviews in Allergy and Immunology,vol.,no.,pp.–,
.
[] E. S. Husebye, Z. M. Sthoeger, M. Dayan et al., "Autoantibodies
to a NRA peptide of the glutamate/NMDA receptor in sera
of patients with systemic lupus erythematosus," Annals of the
Rheumatic Diseases,vol.,no.,pp.–,.
[] T. Yoshio, K. Onda, H. Nara, and S. Minota, "Association of IgG
anti-NR glutamate receptor antibodies in cerebrospinal uid
with neuropsychiatric systemic lupus erythematosus," Arthritis
&Rheumatism , vol. , no. , pp. –, .
[] J. G. Hanly, J. Robichaud, and J. D. Fisk, "Anti-NR glutamate
receptor antibodies and cognitive function in systemic lupus
erythematosus," Journal of Rheumatology ,vol.,no.,pp.
–, .
[] G. Franchin, M. Son, S. J. Kim, I. Ben-Zvi, J. Zhang, and B.
Diamond, "Anti-DNA antibodies cross-react with Cq," e
Journal of Autoimmunity,vol.,pp.–,.
[] E. J. ter Borg, G. Horst, P. C. Limburg, and C. G. M. Kallenberg,
"Shis of anti-Sm-specic antibodies in patients with syste-
mic lupus erythematosus: analysis by counter-immunoelectro-
phoresis, immunoblotting and RNA-immunoprecipitation,"
e Journal of Autoimmunity,vol.,no.,pp.–,.
[]W.J.Habets,D.J.deRooij,M.H.Hoet,L.B.vandePutte,
and W. J. van Venrooij, "Quantitation of anti-RNP and anti-
Sm antibodies in MCTD and SLE patients by immunoblotting,"
Clinical & Expe rimental Immunology,vol.,no.,pp.–,
.
[] Z.Amoura,H.Chabre,J.F.Bach,andS.Koutouzov,"Antinucle-
osome antibodies and systemic lupus erythematosus," Advances
in Nephrology from the Necker Hospital,vol.,pp.–,
.
[] J. van der Vlag and J. H. M. Berden, "Lupus nephritis: role of
antinucleosome antibodies," Seminars in Nephrology,vol.,no.
, pp. –, .
Autoimmune Diseases
[] A. J. Ullal, C. F. Reich III, M. Clowse et al., "Microparticles
as antigenic targets of antibodies to DNA and nucleosomes in
systemic lupus erythematosus," e Journal of Autoimmunity,
vol.,no.-,pp.–,.
[] S. Saisoong, S. Eiam-Ong, and O. Hanvivatvong, "Correlations
between antinucleosome antibodies and anti-double-stranded
DNA antibodies, C, C, and clinical activity in lupus patients,"
Clinical and Experimental Rheumatology,vol.,no.,pp.–
, .
[] Z.Amoura,J.C.Piette,J.F.Bach,andS.Koutouzov,"ekey
role of nucleosomes in lupus," Arthritis & Rheumatism ,vol.,
pp. –, .
[] R.W.Burlingame,M.L.Boey,G.Starkebaum,andR.L.Rubin,
"e central role of chromatin in autoimmune responses to
histones and DNA in systemic lupus erythematosus," e Jour-
nal of Clinical Investigation,vol.,no.,pp.–,.
[] K.P.Ng,J.J.Manson,A.Rahman,andD.A.Isenberg,"Asso-
ciation of antinucleosome antibodies with disease are in sero-
logically active clinically quiescent patients with systemic lupus
erythematosus," Arthritis & Rheumatism ,vol.,no.,pp.–
, .
[] D. J. Wallace, H. C. Lin, G. Q. Shen, and J. B. Peter, "Antibodies
to histone (Ha-Hb)-DNA complexes in the absence of anti-
bodies to double-stranded DNA or to (Ha-Hb) complexes are
more sensitive and specic for scleroderma-related disorders
than for lupus," Arthritis & Rheumatism,vol.,no.,pp.–
, .
[] A.Parodi,M.Drosera,L.Barbieri,andA.Rebora,"Antihistone
antibodies in scleroderma," Dermatology,vol.,no.,pp.–
, .
[] S. Vasoo, "Drug-induced lupus: an update," Lupus ,vol.,no.
, pp. –, .
[] R. L. Rubin, "Drug-induced lupus," To xi colog y ,vol.,no.,
pp.–,.
[] S. Minota, T. Yoshio, M. Iwamoto et al., "Selective accumulation
of anti-histone antibodies in glomeruli of lupus-prone Ipr mice,"
Clinical Immunology and Immunopathology,vol.,no.,pp.
–, .
[] M. Sui, Q. Lin, Z. Xu et al., "Simultaneous positivity for anti-
DNA, anti-nucleosome and anti-histone antibodies is a marker
for more severe lupus nephritis," JournalofClinicalImmu-
nology,vol.,no.,pp.–,.
[] M. Reichlin, "Signicance of the Ro antigen system," Journal of
Clinical Immunology,vol.,no.,pp.–,.
[] F. Furukawa, M. Kashihara-Sawami, M. B. Lyons, and D. A.
Norris, "Binding of antibodies to the extractable nuclear anti-
gens SS-A/Ro and SS-B/La is induced on the surface of human
keratinocytes by ultraviolet light (UVL): implications for the
pathogenesis of photosensitive cutaneous lupus," Journal of
Investigative Dermatology,vol.,no.,pp.–,.
[] T. D. Golan, K. B. Elkon, A. E. Gharavi, and J. G. Krueger,
"Enhanced membrane binding of autoantibodies to cultured
keratinocytes of systemic lupus erythematosus patients aer
ultraviolet B/ultraviolet A irradiation," e Journal of Clinical
Investigation, vol. , no. , pp. –, .
[] E. Alexander, J. P. Buyon, T. T. Provost, and T. Guarnieri, "Anti-
Ro/SS-A antibodies in the pathophysiology of congenital heart
block in neonatal lupus syndrome, an experimental model:
in vitro electrophysiologic and immunocytochemical studies,"
Arthritis & Rheumatism,vol.,no.,pp.–,.
[] R. Cimaz, D. L. Spence, L. Hornberger, and E. D. Silverman,
"Incidence and spectrum of neonatal lupus erythematosus:
a prospective study of infants born to mothers with anti-ro
autoantibodies," Journal of Pediatrics ,vol.,no.,pp.–
, .
[] E. Jaeggi, C. Laskin, R. Hamilton, J. Kingdom, and E. Silver-
man, "e importance of the level of maternal Anti-Ro/SSA
antibodies as a prognostic marker of the development of cardiac
neonatal lupus erythematosus. A prospective study of
antibody-exposed fetuses and infants," Journal of the American
College of Cardiology, vol. , no. , pp. –, .
[] C. B. Mond, M. G. E. Peterson, and N. F. Rotheld, "Correlation
of anti-Ro antibo dy with photosensitivity rash in systemic lupus
erythematosus patients," Arthritis & Rheumatism,vol.,no.,
pp. –, .
[] D. P. McCaulie, "Cutaneous diseases in adults associated with
Anti-Ro/SS-Aautoantibody production," Lupus ,vol.,no.,pp.
–, .
[] M. V. Fukuda, S. C. Lo, C. S. de Almeida, and S. K. Shinjo, "Anti-
Ro antibody and cutaneous vasculitis in systemic lupus ery-
thematosus," Clinical Rheumatology ,vol.,no.,pp.–,
.
[] S. Praprotnik, B. Bozic, T. Kveder, and B. Rozman, "Fluctuation
of anti-Ro/SS-A antibody levels in patients with systemic lupus
erythematosus and Sjogren's syndrome: a prospective study,"
Clinical and Experimental Rheumatology,vol.,no.,pp.–
, .
[]E.Scopelitis,J.J.BiundoJr.,andM.A.Alspaugh,"Anti-SS-
A antibody and other antinuclear antibodies in systemic lupus
erythematosus," Arthritis & Rheumatism ,vol.,no.,pp.–
, .
[] R. H. W. M. Derksen and J. F. Meilof, "Anti-Ro/SS-A and
anti-La/SS-B autoantibody levels in relation to systemic lupus
erythematosus disease activity and congenital heart block: a
longitudinal study comprising two consecutive pregnancies
in a patient with systemic lupus erythematosus," Arthritis &
Rheumatism,vol.,no.,pp.–,.
[] M. Wahren, P. Tengn´
er, I. Gunnarsson et al., "Ro/SS-A and
La/SS-BantibodylevelvariationinpatientswithSjogren's
syndrome and systemic lupus erythematosus," e Journal of
Autoimmunity, vol. , no. , pp. –, .
[] A. B. Hassan, I. E. Lundberg, D. Isenberg, and M. Wahren-
Herlenius, "Serial analysis of Ro/SSA and La/SSB antibody
levels and correlation with clinical disease activity in patients
with systemic lupus erythematosus," Scandinavian Journal of
Rheumatology, vol. , no. , pp. –, .
[] A.Menendez,J.Gomez,E.Escanlar,L.Caminal-Montero,and
L. Mozo, "Clinical associations of anti-SSA/Ro and anti-
Ro/TRIM antibodies: diagnostic utility of their separate
detection," Autoimmunity ,vol.,no.,pp.–,.
[] N. Costedoat-Chalumeau, Z. Amoura, E. Villain, L. Cohen,
and J.-C. Piette, "Anti-SSA/Ro antibodies and the heart: more
than complete congenital heart block? A review of electro-
cardiographic and myocardial abnormalities and of treatment
options," Arthritis Research & erapy ,vol.,no.,pp.–,
.
[] W.J.vanVenrooij,R.L.Slobbe,andG.J.M.Pruijn,"Structure
and function of La and Ro RNPs," Molecular Biology Reports ,
vol. , no. , pp. –, .
[] J.B.Harley,"AutoantibodiesinSj ¨
ogren's syndrome," e Journal
of Autoimmunity,vol.,no.,pp.–,.
[] K.Elkon,S.Skelly,andA.Parnassa,"Identicationandchem-
ical synthesis of a ribosomal protein antigenic determinant
Autoimmune Diseases
in systemic lupus erythematosus," Proceedings of the National
Academy of Sciences of the United States of America,vol.,no.
, pp. –, .
[] C. Briani, M. Lucchetta, A. Ghirardello et al., "Neurolupus
is associated with anti-ribosomal P protein antibodies: an
inception cohort study," e Journal of Autoimmunity ,vol.,
no. , pp. –, .
[] M. Mahler, K. Kessenbrock, M. Szmyrka et al., "International
multicenter evaluation of autoantibodies to ribosomal P pro-
teins," Clinical and Vaccine Immunology,vol.,no.,pp.–,
.
[] E. Toubi and Y. Shoenfeld, "Clinical and biological aspects
of anti-P-ribosomal protein autoantibodies," Autoimmunity
Reviews,vol.,no.,pp.–,.
[] A. Katzav, I. Solodeev, O. Brodsky et al., "Induction of autoim-
mune depression in mice by anti-ribosomal P antibodies via the
limbic system," Arthritis & Rheumatism,vol.,no.,pp.–
, .
[] S.Matus,P.V.Burgos,M.Bravo-Zehnderetal.,"Antiribosomal-
P autoantibodies from psychiatric lupus target a novel neuronal
surface protein causing calcium inux and apoptosis," e Jour-
nal of Experimental Medicine,vol.,no.,pp.–,
.
[] L. Caponi, C. Anzilotti, G. Longombardo, and P. Migliorini,
"Antibodies directed against ribosomal P proteins cross-react
with phospholipids," Clinical & Experimental Immunology ,vol.
, no. , pp. –, .
[] F.B.Karassa,A.Afeltra,A.Ambrozicetal.,"Accuracyofanti-
ribosomal P protein antibody testing for the diagnosis of neu-
ropsychiatric systemic lupus erythematosus: an international
meta-analysis," Arthritis & Rheumatism ,vol.,no.,pp.–
, .
[] V. A. Wasserman, A. Niesser, and C. Bruck, "Eine sierdiagnos-
tische Reaction bei Syphilis," Deutsche Medizinische Wochen-
schri,vol.,pp.–,.
[] M. D. Pangbor, "A new serologically active phospholipid from
beef heart," Proceedings of the Society for Experimental Biology
and Medicine,vol.,pp.–,.
[] C. L. Conley and R. C. Hartmann, "A hemorrhagic disorder
caused by circulating anticoagulant in patients with dissemi-
nated lupus erythematosus," e Journal of Clinical Investiga-
tion,vol.,pp.–,.
[] D. I. Feinstein and S. I. Rapaport, "Acquired inhibitors of blood
coagulation," Progress in Hemostasis and rombosis ,vol.,pp.
–, .
[] J.E.Hunt,H.P.McNeil,G.J.Morgan,R.M.Crameri,andS.
A. Krilis, "A phospholipid-beta -glycoprotein I complex is an
antigen for anticardiolipin antibodies occurring in autoimmune
disease but not with infection," Lupus ,vol.,no.,pp.–,
.
[] K. B. M. Reid, "Cq," Methods in Enzymology,vol.,pp.–
, .
[] C. Bigler, M. Schaller, I. Perahud, M. Ostho, and M. Trende-
lenburg, "Autoantibodies against complement Cq specically
target Cq bound on early apoptotic cells," Journal of Immunol-
ogy,vol.,no.,pp.–,.
[] V. M. Holers, "Anti-Cq autoantibodies amplify pathogenic
complement activation in systemic lupus erythematosus," e
Journal of Clinical Investigation,vol.,no.,pp.–,.
[]G.Moroni,M.Trendelenburg,N.DelPapaetal.,"Anti-
Cq antibodies may help in diagnosing a renal are in lupus
nephritis," American Journal of Kidney Diseases,vol.,no.,
pp. –, .
[] M.A.Seelen,L.A.Trouw,andM.R.Daha,"Diagnosticandpro-
gnostic signicance of anti-Cq antibodies in systemic lupus
erythematosus," Current Opinion in Nephrology and Hyperten-
sion,vol.,no.,pp.–,.
[] C. G. M. Kallenberg, "Anti-Cq autoantibodies," Autoimmunity
Reviews,vol.,no.,pp.–,.
[] M.P.Keith,C.Moratz,andG.C.Tsokos,"Anti-RNPimmunity:
implications for tissue injury and the pathogenesis of connec-
tive tissue disease," Autoimmunity R eviews ,vol.,no.,pp.–
, .
[] P. Migliorini, C. Baldini, V. Rocchi, and S. Bombardieri, "Anti-
Sm and anti-RNP antibodies," Autoimmunity ,vol.,no.,pp.
–, .
[] Y. Tokano, M. Yasuma, S. Harada et al., "Clinical signicance of
IgG subclasses of anti-Sm and U ribonucleoprotein antibodies
in patients with systemic lupus erythematosus and mixed
connective tissue disease," Journal of Clinical Immunology,vol.
, no. , pp. –, .
[] A.Doria,A.Ruatti,A.Calligaroetal.,"Antiphospholipidanti-
bodies in mixed connective tissue disease," Clinical Rheumatol-
ogy, vol. , no. , pp. –, .
[] Y. Takahashi, S. Haga, Y. Ishizaka, and A. Mimori, "Autoan-
tibodies to angiotensin-converting enzyme in patients with
connective tissue diseases," Arthritis Research & erapy,vol.
, no. , article R, .
[] L. Iaccarino,M. Gatto, S. Bettio et al., "Overlap connective tissue
disease syndromes," Autoimmunity Reviews ,vol.,no.,pp.
–, .
[] L. M. Amezcua-Guerra, R. Springall, R. Marquez-Velasco, L.
G´
omez-Garc ´
ıa, A. Vargas, and R. Bojalil, "Presence of anti-
bodies against cyclic citrullinated peptides in patients with
"rhupus": a cross-sectional study," Arthritis Research & erapy ,
vol.,no.,articleR,.
[] J. A. Sim´
on,J.Granados,J.Cabiedes,J.R.Morales,andJ.
A. Varela, "Clinical and immunogenetic characterization of
Mexican patients with 'rhupus'," Lupus ,vol.,no.,pp.–
, .
... They are present in patients with Sjögren's syndrome as well as in patients with systemic lupus erythematosus (10-20%). In Sjögren's syndrome, antibodies against SS-B/La are almost always present together with antibodies against SS-A/Ro [41]. The presence of anti-La antibodies in the absence of anti-Ro antibodies is very uncommon, and cases of CHB associated with only anti-La antibody positivity make up less than 1% of the incidence of autoimmune CHB in the literature [42]. ...
... Their titers may fluctuate and persist during the disease activity, often also during clinical remissions, but their titers frequently decrease or disappear during periods of improvement. They may also be present in patients with systemic lupus erythematosus, rheumatoid arthritis, or Sjögren's syndrome, but in these patients, their titer does not correlate with the activity of the disease [41]. Antibodies against nuclear ribonucleoprotein (nRNP) detected by indirect immunofluorescence (antigen-tissue substrates and HEp 2 cells) give a speckled (granular) type of light. ...
- Malgorzata Gryka-Marton
-
![Dariusz Szukiewicz]()
- Justyna Teliga-Czajkowska
- Marzena Olesińska
Neonatal lupus erythematosus (NLE) is a syndrome of clinical symptoms observed in neonates born to mothers with antibodies to soluble antigens of the cell nucleus. The main factors contributing to the pathogenesis of this disease are anti-Sjögren Syndrome A (anti-SS-A) antibodies, known as anti-Ro, and anti-Sjögren Syndrome B (anti-SS-B) antibodies, known as anti-La. Recent publications have also shown the significant role of anti-ribonucleoprotein antibodies (anti-RNP). Seropositive mothers may have a diagnosed rheumatic disease or they can be asymptomatic without diagnosis at the time of childbirth. These antibodies, after crossing the placenta, may trigger a cascade of inflammatory reactions. The symptoms of NLE can be divided into reversible symptoms, which concern skin, hematological, and hepatological changes, but 2% of children develop irreversible symptoms, which include disturbances of the cardiac stimulatory and conduction system. Preconceptive care and pharmacological prophylaxis of NLE in the case of mothers from the risk group are important, as well as the monitoring of the clinical condition of the mother and fetus throughout pregnancy and the neonatal period. The aim of this manuscript is to summarize the previous literature and current state of knowledge about neonatal lupus and to discuss the role of anti-Ro in the inflammatory process.
... Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by autoreactive B and T cells and production of a broad and heterogeneous group of autoantibodies (Cozzani et al, 2014). ...
... Antihistone is an antibodies to histones, proteins that help to lend structure to DNA. It is usually found in both people with druginduced lupus and people with systemic lupus (Cozzani et al, 2014). However, it was not specific enough to systemic lupus to be used as a diagnostic marker. ...
... Because of their high frequency (between 70% and 98%), sensitivity, and specificity, the presence of these autoantibodies may be used to practically diagnose SLE (57.3 percent and 97.4 percent, respectively) [19]. They are exceedingly unlikely to be detected in other pathological disorders or in stable subjects (less than 0.5 percent ) [20]. Additionally, Anti-dsDNA antibodies were discovered in SLE patients several years before illness manifestation, indicating that they are implicated in the progression of a clinically evident disease. ...
... Prevalence of anti-P antibody in SLE patients ranges from 10%-40% and varies with ethnicity, antigen reactivity, and system of detection (7,21,22). In our patients, its prevalence was 25.76%, which is similar to that reported in previous studies. ...
Background Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by heterogeneous pathogenesis, various clinical manifestations, and a broad spectrum of autoantibodies which recognize different cellular components. This study examines the clinical significance and serological associations of serum antiribosomal P antibodies (anti-P) derived from SLE patients in a population from southwestern Colombia. Methods We performed a cross-sectional study of 66 SLE patients. Serum antiribosomal P0 autoantibodies were detected by line immunoassay using the ANA-LIA MAXX kit and processed on the automated HumaBlot 44FA system (Human Diagnostics, Germany). Results Of the 66 SLE patients included in the study, 17 patients (25.76%) showed anti-P positivity by line immunoassay (IA), 47 (71.21%) were negative, and results from 2 patients were indeterminate. We did not find an association with neuropsychiatric SLE (NPSLE), renal, or hepatic disorders (P > 0.05). Laboratory findings indicated that anti-P positivity was significantly associated to anti-Smith (P = 0.001), anti-Ro60/SSA (P = 0.046), and anti-dsDNA antibodies (P = 0.034), the latter being true only when performed using indirect immunofluorescence (IIF). Conclusion The anti-P antibodies are not associated with clinical manifestations such as NPSLE, lupus nephritis, or hepatic involvement in the southwest Colombian SLE population. Moreover, we confirmed previously reported association between anti-P antibody, serum anti-dsDNA, and anti-Smith.
... 5 Anti-double stranded DNA antibody showed high specificity (92%-96%), but sensitivity is very moderate for SLE (only 57%-67%). 6 Therefore, identification of SLE early diagnostic biomarkers and making it a useful new tool are unmet medical needs. ...
- Jiaxi Chen
- Chong Liu
- Shenyi Ye
- Jiaqin Xu
Global lipidomics is of considerable utility for exploring altered lipid profiles and unique diagnostic biomarkers in diseases. We aim to apply ultra‐performance liquid chromatography‐tandem mass spectrometry to characterize the lipidomics profile in systemic lupus erythematosus (SLE) patients and explore the underlying pathogenic pathways using the lipidomics approach. Plasma samples from 18 SLE patients, 20 rheumatoid arthritis (RA) patients, and 20 healthy controls (HC) were collected. A total of 467 lipids molecular features were annotated from each sample. Orthogonal partial least square‐discriminant analysis, K‐mean clustering analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated disrupted lipid metabolism in SLE patients, especially in phospholipid, glycerol, and sphingolipid metabolism. The area under curve (AUC) of lipid metabolism biomarkers was better than SLE inflammation markers that ordinarily used in the clinic. Proposed model of monoglyceride (MG) (16:0), MG (18:0), phosphatidylethanolamine (PE) (18:3–16:0), PE (16:0–20:4), and phosphatidylcholine (PC) (O‐16:2–18:3) yielded AUC 1.000 (95% CI, 1.000–1.000), specificity 100% and sensitivity 100% in the diagnosis of SLE from HC. A panel of three lipids molecular PC (18:3‐18:1), PE (20:3–18:0), PE (16:0–20:4) permitted to accurately diagnosis of SLE from RA, with AUC 0.921 (95% CI, 0.828–1.000), 70% specificity, and 100% sensitivity. The plasma lipidomics signatures could serve as an efficient and accurate tool for early diagnosis and provide unprecedented insight into the pathogenesis of SLE.
... 3 SLE is characterised by the production of a variety of auto-antibodies owing to the presence of autoreactive B and T cells. 5 The anti-dsDNA is considered a specific marker for SLE and observed in 70-98% of patients. 6 Our case was diagnosed as SLE based on the ANA pattern and the presence of anti-double strand DNA. ...
- Sudha V Damarla
-
![Upputuri Brahmaiah]()
Systemic lupus erythematosus is an autoimmune connective tissue disorder that has well established cutaneous features and typically affects women. However, isolated bilateral periorbital involvement is a rare clinical presentation of systemic lupus erythematosus, which may often delay the diagnosis and treatment. We report such a case in a 20-year-old male.
- Shane Murray
- Yousaf Ali
Joint pain is one of the most common presentations to primary care, and the differentiation between inflammatory and mechanical causes can be challenging. Since autoimmune diseases make up a significant proportion of these patients, serologic testing is important in both diagnosis and clinical decision-making. Unfortunately, due to the presence of autoantibodies in a healthy population, these tests are often perceived as confusing. This chapter will focus on the diagnostic interpretation of normal and abnormal rheumatologic values.
Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by the formation of antigen–antibody complexes which trigger an immune response. We investigate certain autoantibodies including nucleosome, double-stranded DNA (dsDNA), Smith, ribonucleoprotein, and Sjögren's syndrome-related antigens, and examine their associations with disease activity, damage accrual, and SLE-related clinical and serological manifestations in patients with SLE. We conducted a cross-sectional study with a total 293 patients (90.4% female, mean age 46.87±12.94 years) and used the Systemic Lupus Erythematosus Disease Activity Index 2000 and Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) to evaluate disease activity and disease-related damage, respectively. Systemic Lupus Erythematosus Disease Activity Index scores were significantly higher in anti-nucleosome-positive (3.87±2.72 vs 2.52±2.76, p=0.004) and anti-dsDNA-positive (3.08±2.91 vs 2.04±2.48, p=0.010) patients compared with patients without these antibodies. SDI scores were also significantly higher in anti-nucleosome-positive patients (1.61±1.99 vs 0.89±1.06, p=0.004). The presence of antinucleosome (p=0.019) and anti-dsDNA antibodies (p=0.001) both correlated significantly with the incidence of nephritis; anti-La antibodies were associated with arthritis (p=0.022), and we also observed a relationship between the presence of antinucleosome antibodies and leukopenia (p=0.011). Patients with antinucleosome or anti-dsDNA antibodies had a higher disease activity and were likely to have nephritis. Antinucleosome was also associated with more damage accrual. A greater understanding of these autoantibodies could lead to the development of new approaches to more accurate assessments of SLE.
- Wei Lin
- Zhifei Xin
- Kenan Peng
- Wen Zhang
Background Associations between anti-ribonucleoprotein (RNP) antibodies status and distinct clinical primary Sjögren's syndrome (pSS) subtypes have not yet been firmly established. The aim of our study i s to determine whether associations exist between RNP antibody status and the clinical manifestations, laboratory features, or disease activity in pSS. Methods A retrospective cohort of 39 anti-RNP antibody-positive and 294 anti-RNP antibody-negative pSS patients was assembled. Data regarding demographic information, glandular and extraglandular manifestations, laboratory findings, and disease activity (scored according to the European League Against Rheumatism SS disease activity index (ESSDAI)) were extracted from patient records. Univariate methods followed by multivariable logistic regression analysis were used to evaluate potential associations between anti-RNP antibody status and clinicopathologic features. Results Patients with anti-RNP antibody-positive pSS had a higher prevalence of Raynaud's phenomenon (RP) and hematological, pulmonary, lymphatic system, and mucocutaneous involvement; higher erythrocyte sedimentation rates and serum IgG levels; lower lymphocytes counts; and significantly higher ESSDAI scores (median (interquartile range): 13 (7–18) versus 7 (3–12), p < 0.001). No significant differences were observed between groups for C-reactive protein levels and rheumatoid factor or anti-Ro/SSA or -La/SSB antibody positivity. Multivariate analysis identified RP, interstitial lung disease (ILD), and lymphatic system involvement as independent predictors of anti-RNP antibody positivity in pSS patients. Conclusions In this cohort, anti-RNP antibodies were associated with several clinicopathologic features of severe pSS, such as RP and hematologic, lymphatic, and pulmonary disorders. Therefore, anti-RNP antibodies may play an important role in the pathogenesis and severity of pSS.
Antinuclear antibodies (ANA) represent a family of autoantibodies targeting ubiquitous cellular constituents and are a hallmark of systemic inflammatory autoimmune rheumatic diseases named connective tissue diseases (CTD). The gold standard method for ANA determination is indirect immunofluorescence (IIF) on the human laryngeal epidermoid carcinoma cell line type 2 substrate (HEp-2), but with increasing demand for ANA testing, novel methods eased for automation emerged, which allows testing by staff less experienced in this specific field of laboratory diagnostic. In 2016 The working group (WG) for laboratory diagnostics of autoimmune diseases as part of the Committee for the Scientific Professional Development of the Croatian Society of Medical Biochemistry and Laboratory Medicine (CSMBLM) published the data of a survey regarding general practice in laboratory diagnostics of autoimmune diseases in Croatia. Results indicated high diversity in the performance of autoantibody testing as well as reporting of the results and indicated the need of creating recommendations for the assessment of ANA that would help harmonize diagnostics of systemic autoimmune rheumatic diseases in Croatia. This document encompasses twenty-seven recommendations for ANA testing created concerning indications for ANA testing, preanalytical, analytical, and postanalytical issues, including rational algorithm and quality control assurance. These recommendations are based on the relevant international recommendations and guidelines for the assessment of ANA testing and relevant literature search and should help to harmonize the approach in ANA testing and clarify differences in interpretation of the results obtained using different methods of determination.
Little information exists about the association of anti-SSA/Ro60 and anti-Ro52/TRIM21 with systemic lupus erytematosus (SLE) features. In this work, we analysed the associations of both anti-Ro reactivities with clinical and immunological manifestations in 141 SLE patients. Photosensitivity and xerophtalmia/xerostomia were found to be positively associated with both anti-SSA/Ro60 (P = 0.024 and P = 0.019, resp.) and anti-Ro52/TRIM21 (P = 0.026 and P = 0.022, resp.). In contrast, a negative association was detected regarding anti-phospholipid antibodies, anti-SSA/Ro60 having a stronger effect (P = 0.014) than anti-Ro52/TRIM21. Anti-SSA/Ro60 showed a specific positive association with hypocomplementemia (P = 0.041), mainly with low C4 levels (P = 0.008), whereas anti-Ro52/TRIM21 was found to be positively associated with Raynaud's phenomenon (P = 0.026) and cytopenia (P = 0.048) and negatively associated with anti-dsDNA (P = 0.013). Lymphocytes are involved in the relationship between anti-Ro52/TRIM21 and cytopenia since positive patients showed lower cell levels than negative patients (P = 0.036). In conclusion, anti-SSA/Ro60 and anti-Ro52/TRIM21 showed both common and specific associations in SLE. These data thus increase evidence of the different associations of the two anti-Ro specificities even in a particular disease.
-
![Marius Teodorescu]()
The recent guidelines for the clinical use of antinuclear antibody tests issued by a Committee of the College of American Pathologists (CAP), suggest widespread misunderstanding of the clinical value of testing for the level of anti-ssDNA (single-stranded DNA or total DNA) IgG antibodies. This misunderstanding may stem from misconceptions about the manner in which clinicians use, in clinical context, immunoassays that have results expressed on a wide numerical scale. When the anti-ssDNA antibody (Ab) test is used for the differential diagnosis of new patients suspected of an inflammatory rheumatic disease the clinical sensitivity for systemic lupus erythematosus (SLE) is close to 100%, and the specificity about 85%. Since anti-dsDNA (double stranded DNA) is present in only about 65% of new SLE patients, an abnormal anti-ssDNA Ab test in the remaining 35% provides the clinician with a valuable clue to search for other criteria for SLE. Contrary to a widely held belief that anti-ss-DNA Ab occurs frequently in patients with rheumatoid arthritis (RA), anti-ssDNA is present only in 10–15% of this patient population and then at relatively low levels. There is evidence that anti-ssDNA, like anti-dsDNA, is involved in the pathogenesis of lupus nephritis. Moreover, the increase in anti-ssDNA Ab level appeared to be the best predictor of forthcoming increase in anti-dsDNA and SLE flare. In a context of symptoms different from those of rheumatic diseases, anti-ssDNA antibodies may be elevated in a relatively high proportion of patients with any of several diseases; leukemia, preeclampsia, chronic hepatitis, renal complications of diabetes, and some inflammatory neurological diseases. In conclusion, anti-ssDNA helps to rule out SLE, helps in the diagnosis of SLE when anti-dsDNA is not present and is useful in follow-up of SLE patients. Like most other quantifiable laboratory indicators of abnormality, anti-ssDNA Ab test is also useful in clinical context for the diagnosis and prognosis of several other condition.
-
![Paolina Quattrocchi]()
- A Barrile
- D Bonanno
- B Ferlazzo
Objective: The aim of our study was to investigate the prevalence and the disease specificity of anti-nucleosome antibodies in systemic lupus erythematosus and their association with disease activity and renal involvement. Methods: Anti-nucleosome antibodies were measured by ELISA in the sera of patients with systemic lupus erythematosus (SLE) (47), rheumatoid arthritis (RA) (22), mixed connective tissue disease (MCTD) (19), systemic sclerosis (SSc) (11) and Siögren 's syndrome (SS) (10). Anti-dsDNA antibodies were measured by UF on Chritidia luciliae. In the patients with SLE serum levels of C3 and C4 complement components were also measured. Sera of 22 healthy individuals were assayed as controls. SLE activity was evaluated by the ECLAM score. Results: Anti-nucleosome antibodies were found in 40 patients with SLE (85.1%), in 10 with RA (45.4%), in 8 with MCTD (42.1%), in 4 with SSc (36.3%), in 1 with SS (10%) and in none of the healthy controls. Anti-dsDNA antibodies were found in 23 patients with SLE and were absent in the patients with other CTD and in controls. All the patients with SLE and renal involvement were positive both for anti-dsDNA antibodies and anti-nucleosome antibodies. No significant correlation was observed between anti-nucleosome antibodies and disease activity and renal involvement. Conclusion: Anti-nucleosome antibodies are present in a high percentage of the patients with SLE but they don't seem to be specific markers of the desease. Our data don't support a clear correlation between anti-nucleosome antibodies and disease activity and renal involvement.
The most widely read textbook in the history of medicine -- made even more essential to practice and education by an unmatched array of multi-media content DVD contains 53 chapters not found in the book, hundreds of bonus illustrations, and important procedural videos Through six decades, no resource has matched the encylopedic scope, esteemed scholarship, and scientific rigor of Harrison's Principles of Internal Medicine. Both an educational tool and a clinical reference, it remains the most universally respected textbook in all of medical publishing and the pinnacle of current medical knowledge. The eighteenth edition of Harrison's features expanded and more in-depth coverage of key issues in clinical medicine, pathophysiology, and medical education. The acclaimed Harrison's DVD has been updated to include 53 chapters not found in the book, all-new procedural videos commissioned especially for Harrison's, a masterpiece video from internationally renowned neurologist Martin Samuels on the neurological exam, and hundreds of bonus videos. Now presented in two volumes New text design greatly enhances readability New chapters on cutting-edge issues in clinical medicine Expanded fovus on global considerations of health and disease More evidence-based than ever How-to videos cover topics such as central venous line placement, endotracheal intubation, pericardiocentesis, and thoracentis NEW print chapters include: World Demographics of Aging The Biology of Aging Clinical Problems of Aging The Human Microbiome Acinetobacter Infections Antiphospholipid Antibody Syndrom NEW DVD-only chapters include: Primary Care in Low and Middle Income Countries Neoplasia During Pregnancy Fluid and Electrolyte Imbalances and Acid-Base Disturbances: Case Examples Less Common Malignancies of Lymphoid Cells Interstitial Cystitis/Painful Bladder Syndrome The Schilling Test War-Related Neuro-Psychiatric Illness High-Altitude Illness The Clinical Laboratory in Modern Healthcare Authoritative Content Essential to Medical Practice and Education: Condensed Table of Contents: Part 1: General Considerations in Clinical Medicine; Part 2: Cardinal Manifestations and Presentation of Disease; Section 1: Pain; Section 2: Alterations in Body Temperature; Section 3: Nervous System Dysfunction; Section 4: Disorders of the Eyes, Ears, Nose, and Throat; Section 5: Alterations in Circulatory and Respiratory Functions; Section 6: Alterations in Gastrointestinal Function; Section 7: Alterations in Renal and Urinary Tract Function; Section 8: Alterations in Sexaul Function and Reproduction; Section 9: Alterations in the Skin; Section 10: Hematologic Alterations; Part 3: Genes, the Environment, and Disease; Part 4: Regenerative Medicine; Part 5: Aging; Part 6: Nutrition; Part 7: Oncology and Hematology; Section 1: Neoplastic Disorders; Section 2: Hematopoietic Disorders; Section 3: Disorders of Hemostasis; Part 8: Infectious Diseases; Section 1: Basic Considerations in Infectious Diseases; Section 2: Clinical Syndromes: Community-Acquired Infections; Section 3: Clinical Syndromes: Health Care Associated Infections; Section 4: Approach to Therapy for Bacterial Diseases; Section 5: Diseases Caused by Gram-Positive Bacteria; Section 6: Diseases Caused by Gram-Negative Bacteria; Section 7: Miscellaneous Bacterial Infections; Section 8: Mycobacterial Diseases; Section 9: Spirochetal Diseases; Section 10: Diseases Caused by Rickettsia, Mycoplasmas, and Chlamydiae; Section 11: Viral Diseases: General Considerations; Section 12: Infections Due to DNA Viruses; Section 13: Infections Due to DNA and RNA Respiratory Viruses; Section 14: Infections Due to Human Immunodeficiency Virus and Other Retroviruses; Section 15: Infections Due to RNA Viruses; Section 16: Fungal and Algal Infections; Section 17: Protozoal and Helminthic Infections: General Considerations; Section 18: Protozoal Infections; Part 9: Terrorism and Clinical Medicine; Part 10: Disorders of the Cardiovascular System; Section 1: Introduction to Cardiovascular Disorders; Section 2: Diagnosis of Cardiovascular Disorders; Section 3: Disorders of Rhythm; Section 4: Disorders of the Heart; Section 5: Vascular Disease; Part 11: Disorders of the Respiratory System; Section 1: Diagnosis of Respiratory Disorders; Section 2: Diseases of the Respiratory System; Section 3: Neurologic Critical Care; Section 4: Oncologic Emergencies; Part 13: Disorders of the Kidney and Urinary Tract; Part 14: Disorders of the Gastrointestinal System; Section 1: Disorders of the Alimentary Tract; Section 2: Liver and Billiary Tract Disease; Section 3: Disorders of the Pancreas; Part 15: Disorders of the Immune System, Connective Tissue and Joints; Section 1: The Immune System in Health and Diseases; Section 2: Disorders of Immune-Mediated Injury; Section 3: Disorders of the Joints and Adjacent Tissues; Part 16: Endocrinology; Section 2: Disorders of Bone and Mineral Metabolism; Section 3: Disorders of Intermediary Metabolism; Part 17: Neurologic Disorders; Section 1: Diagnosis of Neurologic Disorders; Section 2: Diseases of the Central Nervous System; Section 3: Nerve and Muscle Disorders; Section 4: Chronic Fatigue Syndrome; Section 5: Psychiatric Disorders; Section 6: Allcoholism and Drug Dependency; Part 18: Poisoning, Drug Overdose, and Evenomation; Part 19: High Altitude and Decompression Sickness
Source: https://www.researchgate.net/publication/260951952_Serology_of_Lupus_Erythematosus_Correlation_between_Immunopathological_Features_and_Clinical_Aspects
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