Diagnostic accuracy of blood B-cell subset profiling and autoimmunity markers in Sjögren’s syndrome

Abstract

The aims of this study were to evaluate the diagnostic accuracy of blood B-cell subset profiling and immune-system activation marker assays in primary Sjogren's syndrome (pSS) and to assess whether adding these tools to the current laboratory item would improve the American-European Consensus Group (AECG) criteria.
In a single-center cohort of patients with suspected pSS, we tested the diagnostic performance of anti-SSA, antinuclear antibody (ANA), rheumatoid factor (RF), gammaglobulins, IgG titers, and B-cell ratio defined as (Bm2 + Bm2[prime])/(eBm5 + Bm5), determined using flow cytometry. The reference standard was a clinical diagnosis of pSS established by a panel of experts.
Of 181 patients included in the study, 77 had pSS. By logistic regression analysis, only ANA >=1:640 (sensitivity, 70.4%; specificity 83.2%) and B-cell ratio >=5 (sensitivity, 52.1%; specificity, 83.2%) showed independent associations with pSS, of similar strength. In anti-SSA-negative patients, presence of either of these two criteria had 71.0% sensitivity but only 67.3% specificity for pSS; whereas combining both criteria had 96.2% specificity but only 12.9% sensitivity. Adding either of these two criteria to the AECG criteria set increased sensitivity from 83.1% to 90.9% but decreased specificity from 97.1% to 85.6%, whereas adding both criteria in combination did not substantially modify the diagnostic performance of the criteria set. The adjunction of RF + ANA >= 1:320, as proposed in the new American College of Rheumatology (ACR) criteria, did not improve the diagnostic value of anti-SSA.
Blood B-cell subset profiling is a simple test that has good diagnostic properties for pSS. However, adding this test, with or without ANA positivity, does not improve current classification criteria.

Full text

R E S E A R C H A R T I C L E Open Access
Diagnostic accuracy of blood B-cell subset
profiling and autoimmunity markers in Sjögren’s
syndrome
Divi Cornec
1,2
, Alain Saraux
1,2
, Jacques-Olivier Pers
2
, Sandrine Jousse-Joulin
1,2
, Thierry Marhadour
1
,
Anne-Marie Roguedas-Contios
3
, Steeve Genestet
4
, Yves Renaudineau
2
and Valérie Devauchelle-Pensec
1,2*
Abstract
Introduction: The aims of this study were to evaluate the diagnostic accuracy of blood B-cell subset profiling and
immune-system activation marker assays in primary Sjögren’s syndrome (pSS) and to assess whether adding these
tools to the current laboratory item would improve the American-European Consensus Group (AECG) criteria.
Methods: In a single-center cohort of patients with suspected pSS, we tested the diagnostic performance of
anti-SSA, antinuclear antibody (ANA), rheumatoid factor (RF), gammaglobulins, IgG titers, and B-cell ratio defined as
(Bm2 + Bm2′)/(eBm5 + Bm5), determined using flow cytometry. The reference standard was a clinical diagnosis of
pSS established by a panel of experts.
Results: Of 181 patients included in the study, 77 had pSS. By logistic regression analysis, only ANA ≥1:640
(sensitivity, 70.4%; specificity 83.2%) and B-cell ratio ≥5 (sensitivity, 52.1%; specificity, 83.2%) showed independent
associations with pSS of similar strength. In anti-SSA-negative patients, presence of either of these two criteria had
71.0% sensitivity but only 67.3% specificity for pSS; whereas combining both criteria had 96.2% specificity but only
12.9% sensitivity. Adding either of these two criteria to the AECG criteria set increased sensitivity from 83.1% to
90.9% but decreased specificity from 97.1% to 85.6%, whereas adding both criteria in combination did not
substantially modify the diagnostic performance of the criteria set. The adjunction of RF + ANA ≥1:320, as proposed
in the new American College of Rheumatology (ACR) criteria, did not improve the diagnostic value of anti-SSA.
Conclusions: Blood B-cell subset profiling is a simple test that has good diagnostic properties for pSS. However,
adding this test, with or without ANA positivity, does not improve current classification criteria.
Introduction
Primary Sjögren’s syndrome (pSS) is a chronic auto-
immune disorder that primarily affects the salivary and
lachrymal glands. B cells play a major role in the patho-
genesis of pSS [1]. Thus, biological markers for B-cell
activity and autoimmunity might help to establish the
diagnosis of pSS.
The main serological markers for pSS are autoanti-
bodies against Ro/SSA or La/SSB ribonucleoproteins.
These markers are the only biological item in the widely
used American-European Consensus Group (AECG)
classification criteria [2]. However, they are present in
only 50% to 75% of patients with pSS [3] and are
frequently encountered in other systemic autoimmune
diseases [4]. Other biological markers may thus be va-
luable for the diagnosis of pSS.
Recently published American College of Rheumatology
(ACR) classification criteria for pSS suggest that positiv-
ity for antinuclear antibodies (ANAs) and rheumatoid
factor (RF) should be considered in patients negative for
anti-Ro/SSA antibodies [5]. ANAs are present in 80% of
patients with pSS and RF in 40% [3]. However, the sensi-
tivity (Se) and specificity (Sp) of these tests for pSS com-
pared to controls with other causes of sicca syndrome
need to be assessed before accepting these as part of a
criteria set.
* Correspondence: valerie.devauchelle-pensec@chu-brest.fr
1
Service de Rhumatologie, Centre Hospitalier Régional et Universitaire de
Brest, Hôpital de la Cavale Blanche, BP 824, F-29609 Brest cedex, France
2
EA 2216 Immunologie et Pathologie, Université de Brest, SFR ScinBios,
Labex Imunotherapy, Graft, Oncology, BP 824, F-29609 Brest cedex, France
Full list of author information is available at the end of the article
© 2014 Cornec et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative
Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and
reproduction in any medium, provided the original work is properly cited.
Cornec et al. Arthritis Research & Therapy 2014, 16:R15
http://arthritis-research.com/content/16/1/R15

B-cell activation may result in hypergammaglobu-
linemia, which is common in patients with pSS [3]. Im-
munoglobulin (Ig)A and IgG are often elevated and can
display RF activity [6].
Sound evidence indicates that the distribution of per-
ipheral-blood B-cell subsets is profoundly altered in pa-
tients with pSS. Memory B cells accumulate in target
epithelial organs, and their proportion is decreased in
peripheral blood [7]. On the other hand, the proportions
of transitional and naive B cells are increased in peri-
pheral blood [8]. IgD/CD38 staining was originally de-
signed for B cell subset study in tonsils, separating
important stages in B-cell development from naive to
memory B cells (Bm1 to Bm5) [9]. This classification is
helpful for studying blood B-cell subset alterations in
pSS: in peripheral blood, Bm2 (IgD+/CD38 low) and
Bm2′(IgD+/CD38 high) populations include mainly
transitional and activated naïve B cells and are increased
in pSS patients, whereas eBm5 (IgD-/CD38 low) and
Bm5 (IgD-/CD38-) populations are memory B cells,
which are less represented in patients with pSS com-
pared to patients with rheumatoid arthritis or normal
control subjects [10]. We previously showed in a case–
control study that these alterations in blood B-cell subset
distributionmayhaveaninterestingdiagnosticvaluefor
pSS. The better item to predict a diagnosis of pSS using
only fluorescence-activated cell sorting (FACS) analysis was
the B-cell ratio defined as (Bm2 + Bm2′)/(eBm5 + Bm5),
which was strongly associated with pSS compared to
rheumatoid arthritis, systemic lupus erythematosus, and
healthy controls [11].
The primary aim of this study was to assess the
diagnostic value of B-cell subset profiling and other bio-
logical autoimmunity markers in a cross-sectional cohort
of patients with suspected pSS. We also evaluated the
diagnostic usefulness of these tools compared to anti-
SSA antibodies and other items of the AECG criteria set.
Methods
Study population
This prospective study was performed in a cohort of pa-
tients with suspected pSS recruited in Brittany, France,
between November 2006 and September 2011 [12]. In-
clusion criteria were subjective ocular or oral dryness,
recurrent or bilateral parotidomegaly, or extraglandular
symptoms suggestive of pSS. The study was approved by
the local medical ethics committee (Brest University
Hospital), and written informed consent was obtained
from all patients before study inclusion.
Clinical and laboratory evaluations
Each patient underwent a standardized assessment inclu-
ding a bilateral Schirmer’s test (abnormal if ≤5mm/5min
on at least one side) and unstimulated salivary flow
measurement (abnormal if <0.1 mL/min); a joint eva-
luation; and a general examination. Laboratory tests in-
cluded serum protein electrophoresis; assays of IgG, IgA,
and IgM; ANA on Hep2 cells, anti-SSA and anti-SSB anti-
bodies using commercial ELISAs, and RF using in-house
ELISA (IgM and IgA isotypes) [6]. Minor labial salivary
gland biopsy (SGB) was graded according to the semi-
quantitative Chisholm and Mason score [13].
Blood B-cell subset profiling
Flow cytometry was performed as previously published
[11]. The Bm2 + Bm2′subset was defined as the IgD +
and CD38low/high population, and the eBm5 + Bm5
subset as the IgD- and CD38negative/low population
(Figure 1). The proportion of these two subsets in the
total CD19+ B-cell population was determined, and
the (Bm2 + Bm2′)/(eBm5 + Bm5) ratio (B-cell ratio) was
computed.
Reference standard
The reference standard was a clinical diagnosis of pSS
performed by the evaluating rheumatologist, based on
the clinical interview and examination, standard biology
and salivary gland biopsy results. All doubtful cases were
reviewed by a panel of three experts, who were blinded
to the results of B-cell profiling. Other systemic diseases
were diagnosed according to published classification
criteria.
Statistical analysis
Statistical tests were performed using the Statistical
Package for the Social Sciences (SPSS 18.0, 2009, SPSS
Inc., Chicago, IL, USA). Quantitative variables are des-
cribed as means ± standard deviation and qualitative va-
riables as numbers (%). We compared patients who
fulfilled the reference standard (clinical diagnosis of pSS)
to those who did not, using Mann–Whitney and chi-
square tests as appropriate. We plotted receiver-operating
characteristic (ROC) curves to determine the optimal
cutoff associated with the best combination of sensitivity
(Se) and specificity (Sp) for each test.
To determine which laboratory tests were independently
associated with a diagnosis of pSS, we performed multiple
logistic regression with backward selection using the likeli-
hood ratio test. All items associated with a diagnosis of
pSS by univariate analysis with Pvalues <0.2 were in-
cluded in this analysis.
Results
Of the 181 patients included in the study (Table 1), 167
(92.2%) were women. Mean age was 56.1 ± 13.0 years and
mean symptom duration was 6.4 ± 6.9 years. Of the 77
patients given a clinical diagnosis of pSS, 64 (83.1%) ful-
filled AECG criteria. All AECG items were significantly
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associated with a diagnosis of pSS except xerophthalmia
and xerostomia. No differences were found between pSS
and non-pSS patients for age, disease duration, or sex
ratio. Other diagnoses were: idiopathic sicca syndrome
(N = 51), other systemic autoimmune diseases (N = 29),
drug-induced sicca syndrome (N = 21), ill-controlled dia-
betes mellitus (N = 2), hepatitis C virus-related sicca syn-
drome (N = 1).
The mean B-cell ratio was significantly higher in the pSS
group than in the non-pSS group (7.4 ± 6.9 vs. 3.2 ± 2.3,
P<0.001). ROC curve analysis (Figure 2) identified ≥5as
the best cutoff, with 52.1% Se and 83.2% Sp. The highest
values of this ratio were strongly suggestive of pSS, with a
cutoff ≥6.5 having 92.6% Sp and a cutoff ≥9 97.9% Sp (with
42.3% and 28.2% Se, respectively). The correlation of
B-cell ratio ≥5 with anti-SSA and abnormal SGB findings,
estimated using Cohen’s kappa coefficient, was moderate
(kappa = 0.35 and 0.30, respectively).
Figure 2 shows the ROC curve analysis for the biological
markers. Their diagnostic value is shown in Table 2. Anti-
SSB antibodies were found in 25 (32.5%) patients with
pSS, all of whom also had anti-SSA antibodies. No patient
had anti-SSA without ANA. ACR 2012 criteria serological
item (anti-SSA/B or (ANA ≥1:320 + positive RF)) did not
perform better than anti-SSA/B alone, but gave more false
positive results.
Thirty patients were diagnosed as pSS but were anti-
SSA negative. Among them, three patients had a normal
SGB, and the diagnosis of pSS was made based on subject-
ive and objective ocular and mouth dryness without other
explanation, high-titer ANA, and suggestive extraglan-
dular manifestations (cutaneous vasculitis, peripheral
neuropathy, interstitial pneumonitis or cytopenia). In this
group of anti-SSA negative pSS patients, the frequency of
the different tests was: 56.7% for ANA ≥1:320; 40.0% for
ANA ≥1:640; 20.0% for IgM-RF; 10.0% for ACR 2012
criteria serological item (anti-SSA/B or (ANA ≥1:320 +
positive RF)); 10.0% for gammaglobulins ≥14 g/l; 16.7% for
IgG ≥14 g/l; and 40.0% for B-cell ratio ≥5.
By logistic regression analysis, only anti-SSA anti-
bodies, ANA ≥1:640 and B-cell ratio ≥5 showed inde-
pendent associations with pSS. Using both ANA ≥1:640
and B-cell ratio ≥5 in combination had 37.7% Se and
96.2% Sp in the overall population but only 12.9% Se in
the anti-SSA-negative subset. Using either ANA ≥1:640
or B-cell ratio ≥5 had 85.7% Se and 67.3% Sp in the
overall group and 71.0% Se in the anti-SSA-negative
subgroup.
Modifying the AECG criteria set by adding either
ANA ≥1:640 or B-cell ratio ≥5 increased Se from 83.1%
to 90.9%, but decreased Sp from 97.1% to 85.6%. Adding
both ANA ≥1:640 and B-cell ratio ≥5 did not signifi-
cantly modify the diagnostic performance of the criteria
set (Se 84.2% vs. 83.1% and Sp 96.1% vs. 97.1%).
Discussion
We assessed the diagnostic performance of autoimmu-
nity and B-cell-related markers for pSS. Although ANA
and RF positivity, hypergammaglobulinemia, IgG eleva-
tion, and altered peripheral-blood B-cell subset distri-
bution were far more common in the patients with pSS
compared to those with other causes of sicca symptoms,
these abnormalities correlated closely with anti-SSA
positivity. Only ANA ≥1:640 and B-cell ratio ≥5 were
Figure 1 Examples of typical blood B-cell subset profiling by
flow cytometry. All analyses are gated on CD19+ B cells. A ratio is
computed between Bm2 + Bm2′(immunoglobulin (Ig)D+/CD38low-high
population) and eBm5 + Bm5 (IgD-/CD38low-negative population)
subset proportions. (a) Primary Sjögren’s syndrome patient, with a ratio
of 17.9. (b) Idiopathic sicca patient, with a ratio of 2.2.
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Table 1 Comparison of pSS and non-pSS patients
Overall pSS No pSS Pvalue
n = 181 n = 77 n = 104
Age (years, mean ± SD) 56.1 ± 13.0 56.3 ± 13.5 55.9 ± 12.7 0.89
Symptom duration (years, mean ± SD) 6.4 ± 6.9 7.0 ± 7.6 6.0 ± 6.3 0.48
Female, n (%) 167 (92.2) 70 (90.9) 97 (93.3) 0.56
Xerophthalmia, n (%) 156 (86.2) 70 (90.9) 86 (82.7) 0.11
Xerostomia, n (%) 166 (91.7) 73 (94.8) 93 (89.4) 0.19
Abnormal Schirmer’s test, n (%) 76 (42.0) 44 (57.1) 32 (30.8) <0.001
Decreased salivary flow, n (%) 80 (44.2) 48 (62.3) 32 (30.8) <0.001
Abnormal salivary gland biopsy, n (%) 75 (41.4) 62 (80.5) 13 (12.5) <0.001
Anti-SSA or -SSB positivity, n (%) 47 (26.0) 47 (61.0) 0 (0.0) <0.001
AECG criteria, n (%) 67 (37.0) 64 (83.1) 3 (2.9) <0.001
Anti-SSA positivity, n (%) 47 (26.0) 47 (61.0) 0 (0.0) <0.001
Anti-SSB positivity, n (%) 25 (13.8) 25 (32.5) 0 (0.0) <0.001
ANA ≥1:320, n (%) 105 (58.0) 62 (80.5) 43 (41.3) <0.001
ANA ≥1:640, n (%) 73 (40.3) 54 (70.1) 19 (18.3) <0.001
IgM-RF positivity, n (%) 56 (30.9) 35 (45.5) 21 (20.2) <0.001
IgA-RF positivity, n (%) 37 (20.4) 32 (41.6) 5 (4.8) <0.001
Gammaglobulins ≥14 g/L, n (%) 44 (24.3) 36 (46.8) 8 (7.7) <0.001
IgG ≥14 g/L, n (%) 47 (26.0) 38 (49.4) 9 (8.7) <0.001
B-cell ratio ≥5, n (%) 59 (32.6) 41 (53.2) 18 (17.3) <0.001
ANA ≥1:320 + IgM-RF, n (%) 39 (21.5) 32 (41.6) 7 (6.7) <0.001
ACR criteria serologic item, n (%) 56 (30.9) 49 (63.6) 7 (6.7) <0.001
pSS, primary Sjögren’s syndrome; AECG, American-European Consensus Group; ANA, antinuclear antibodies; Ig, immunoglobulin; RF, rheumatoid factor; ACR criteria
serologic item: (anti-SSA/B or (ANA ≥1:320 + IgM-RF)). Xerophthalmia and xerostomia referred to subjective complaints by the patients. Schirmer’s test was considered
abnormal if ≤5 mm/5 min and unstimulated salivary flow if ≤0.1 mL/min. Salivary gland biopsies were graded according to Chisholm and Mason. Mann–Whitney and
chi-square tests were used as appropriate to compare pSS and non-pSS patients. P<0.05 was considered significant.
Figure 2 ROC curve analysis. The best cutoff for each test is chosen as the best combination of sensitivity and specificity. ROC, receiver-operating
characteristic; ANA, antinuclear antibodies; RF, rheumatoid factor; Ig, immunoglobulin.
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associated with pSS independently from anti-SSA anti-
bodies. However, adding these two tests to the currently
used AECG classification criteria did not improve their
diagnostic performance.
Classification criteria are developed as research tools
for establishing homogeneous patient groups with well-
defined conditions and for comparing different studies,
but they are widely used in clinical practice for diagnos-
tic purposes. However, clinicians may diagnose a disease
in patients who do not meet the classification criteria,
especially those with recent-onset or mild symptoms.
We studied a cohort of patients who reflected the diag-
nostic conditions encountered in everyday clinical prac-
tice, since they were referred to a specialized center
for the evaluation of suspected pSS. The diagnosis was
established by consensus among three experts indepen-
dently from the classification criteria. This study design
allowed us to assess the diagnostic performance of vari-
ous tests and of the AECG criteria in the real-life setting.
We previously used this methodology to study the diag-
nostic performance of salivary gland ultrasonography for
pSS [12].
However, this methodology induces mandatorily a cer-
tain part of circular reasoning, since the experts in their
own minds gave probably more weight for their diagno-
sis to known and objective features of pSS, such as anti-
SSA antibodies or SGB biopsy results. If the experts
would have taken into account the results of B-cell ratio
(to which they were blinded) to make their diagnosis,
they would probably have considered some patients as
pSS due to a high B-cell ratio, which would have im-
proved the diagnostic value of the test in this study.
Flow cytometry is simple, reproducible, and widely avai-
lable. A high (Bm2 + Bm2′)/(eBm5 + Bm5) ratio is far
more common in pSS both compared to other rheumatic
diseases, as reported in our previous study [11], and
compared to sicca syndromes not due to pSS, as shown
here. Higher ratio values are associated with a higher
probability of pSS. Thus, in the individual patient, this test
is valuable. However, its diagnostic weight seems small
compared to the other items of the AECG classification
criteria set.
The abnormal distribution of blood B-cell subsets dur-
ing pSS has previously been explored in regard to the
disease pathophysiology. The decrease in blood memory
B cells in pSS patients may be explained by their accu-
mulation within salivary glands. Indeed, this variation
partly reflects their migration into the exocrine glands of
the patients [7], as well as into their skin [14]. We had
previously observed that Bm2/Bm2′cells express CD19
at 55% and 61% higher levels than the same cell subsets
in normal controls [8]. Such marked increases could
be related to pathogenesis, since modest increases in the
density of CD19 are sufficient to shift the balance bet-
ween tolerance and autoimmunity [15]. To address the
functional significance of the observed phenotype ano-
malies, the dynamic translocation of protein into lipid
rafts was also explored, since these domains are critical
for proximal B cell receptor (BCR) signal transduction.
The results revealed that the association of the BCR with
the lipid rafts was prolonged in pSS. This may be
accounted for by the overexpression of CD19, which
prolongs signaling or prevents the recruitment of nega-
tive regulators, whether such regulators are insufficient
(CD32) or altered (CD45) [8]. As such, changes in the
lipid raft dynamics might lead to an aberrant B-cell
response in pSS. Finally, these perturbations in B-cell
homeostasis in pSS are closely correlated with the dys-
regulation of various cytokines regulating B-cell survival
and activation, such as BAFF [8] and FLT3L [16].
ANA are frequent in patients with pSS. In the new
preliminary ACR classification criteria set proposed by
Shiboski et al. [5], the required ANA titer is 1:320, but
this cutoff was chosen by consensus among experts and
the article does not report a detailed Se and Sp analysis.
In our study, the higher ANA titer of ≥1:640 was re-
quired to obtain the best combination of Se and Sp, and
was associated with pSS independently from anti-SSA
positivity. RF, and especially IgA-RF, are far more fre-
quent in patients with pSS compared to controls. How-
ever, this test correlates strongly with anti-SSA positivity.
Considering ANA titer and RF positivity beside anti-SSA
for the diagnosis of pSS do not seem useful.
Conclusions
This study shows that biological evidence of auto-
immunity is common in patients with pSS but is closely
related to the presence of anti-SSA antibodies. Anti-SSA
remains the main serological tool for diagnosing pSS.
Other serological markers should be tested in cohorts of
Table 2 Diagnostic value of the biological items
Sensitivity Specificity PPV NPV
Anti-SSA or -SSB positivity 61.0% 100% 100% 79.9%
Anti-SSA positivity 61.0% 100% 100% 79.9%
Anti-SSB positivity 32.5% 100% 100% 66.7%
ANA ≥1:320 80.5% 58.7% 59.0% 80.3%
ANA ≥1:640 70.1% 81.7% 74.0% 78.7%
IgM-RF positivity 45.5% 79.8% 62.5% 66.4%
IgA-RF positivity 41.6% 95.2% 86.5% 68.8%
Gammaglobulins ≥14 g/L 46.8% 92.3% 81.8% 70.1%
IgG ≥14 g/L 49.4% 91.3% 80.9% 70.9%
B-cell ratio ≥5 53.2% 82.7% 69.5% 70.5%
ACR criteria serologic item 63.6% 93.7% 87.5% 77.6%
PPV, positive predictive value; NPV, negative predictive value; ANA, antinuclear
antibodies; Ig, immunoglobulin; RF, rheumatoid factor; American College of
Rheumatology (ACR) criteria serologic item: (anti-SSA/B or (ANA ≥1:320 + IgM-RF)).
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patients with suspected pSS. The development of new
classification criteria for pSS has been the focus of an
international debate since the publication of the ACR
2012 criteria [17,18], and we believe that our cohort of
patients with suspected pSS should be useful to validate
such criteria.
Abbreviations
ACR: American College of Rheumatology; AECG: American-European
Consensus Group; ANA: antinuclear antibody; Ig: immunoglobulin;
pSS: primary Sjögren’s syndrome; RF: rheumatoid factor; ROC: receiver-
operating characteristic; Se: sensitivity; SGB: salivary gland biopsy;
Sp: specificity.
Competing interests
The authors have no competing interests to declare concerning this work.
Authors’contributions
DC, AS and VDP designed the study. DC, AS, JOP, SJJ, TM, AMRC, SG, YR and
VDP participated in the management of the patients and their recruitment in
the cohort, and in the acquisition of data. JOP and YR performed the
biological assays. DC and AS performed the statistical analysis. DC and VDP
drafted the manuscript. AS, JOP, SJJ, TM, AMRC, SG and YR critically revised
the manuscript. All authors read and approved the final manuscript, and
agree to be accountable for all aspects of the work.
Author details
1
Service de Rhumatologie, Centre Hospitalier Régional et Universitaire de
Brest, Hôpital de la Cavale Blanche, BP 824, F-29609 Brest cedex, France.
2
EA
2216 Immunologie et Pathologie, Université de Brest, SFR ScinBios, Labex
Imunotherapy, Graft, Oncology, BP 824, F-29609 Brest cedex, France.
3
Service
de Dermatologie, Centre Hospitalier Régional et Universitaire de Brest,
Hôpital Morvan, BP 824, F-29609 Brest cedex, France.
4
Explorations
Fonctionnelles Neurologiques, Centre Hospitalier Régional et Universitaire de
Brest, Hôpital de la Cavale Blanche, BP 824, F-29609 Brest cedex, France.
Received: 29 July 2013 Accepted: 30 December 2013
Published: 17 January 2014
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doi:10.1186/ar4442
Cite this article as: Cornec et al.:Diagnostic accuracy of blood B-cell
subset profiling and autoimmunity markers in Sjögren’s syndrome.
Arthritis Research & Therapy 2014 16:R15.
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