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Beyond the paradigm that T lymphocytes exert strict control over them, B lymphocytes have recently been assigned numerous functions. 1 Therefore, they are not confined anymore to anti- body production. Rather, evidence accumulates that they govern immune responses to self and non-self-antigen through antibody-dependent as well as antibody-independent mechanisms. An inference from such a sudden awareness is that systemic lupus erythematosus (SLE), rheuma- toid arthritis (RA) and primary Sjogren's syndrome (SS), long viewed as T cell-driven conditions, are being re-examined from the outset. Thus, this review ventures into the area of the relationships between autoimmune processes and B lymphocytes. The evidence that B cells are the culprits in SLE, RA and primary SS may be listed under three head- ings, following recent major breakthroughs in their study. The first is the demonstration that the CD5 molecule acts as a regulator for their activities; the second, the dissection of B-lymphocyte subsets; and the third, the report of two supplemental tumour- necrosis factor (TNF) family members. One is referred to as BAFF, for B cell-activating factor of the TNF family, and the other as APRIL, for a proliferation-inducing ligand. No doubt, develop- ing insights into B lymphocyte commitment in non- organ-specific autoimmune diseases should bring about new therapeutic approaches. The CD5 control of B lymphocytes A T cell marker has been found on the B cells from patients with chronic lymphocytic leukaemia, and subsequently identified as CD5. The B-cell

The Sjögren's syndrome is a systemic autoimmune disease characterized by lymphocytic infiltration of the glands responsible for mouth and eyes dryness. A minority of infiltrating B cells is organized as germinal centers while the majority is aggregated into clusters of transitional and marginal zone B cells. The Toll-like receptor 9 (TLR9) recognizes microbial DNA but also, sometimes, the self DNA. It appears to be a key determinant of the survival and differentiation of B lymphocytes. After laser micro-dissection of B cells from salivary glands, analyses by quantitative RT-PCR showed that transitional B cells express high level of TLR9 mRNA unlike B cells from germinal centers. B lymphocytes from healthy donors were sorted by flow cytometry and stimulated in vitro with their TLR9. It induces survival, activation and proliferation associated with phenotypic changes. Transitional B cells exhibited characteristics of the marginal zone, whereas mature B cells expressed follicular germinal center specificities. Finally, IgM and IgG were secreted by both population, but with elevated production of autoantibodies by the transitional B cells. Increased expression of TLR9 by transitional B cells suggests that they may be highly sensitive to differentiate into autoantibody secreting cells through maturation into the marginal zone into the salivary glands. TLR9 might be a target for forthcoming biotherapies. Le syndrome de Gougerot-Sjögren est une maladie autoimmune systémique caractérisée par une infiltration lymphocytaire des glandes responsable d'une sécheresse buccale et oculaire. Une minorité des lymphocytes B infiltrants est organisée en centres germinatifs tandis que la majorité est regroupée en agrégats de lymphocytes B transitionnels et de la zone marginale. Le Toll-like receptor 9 (TLR9) reconnaît l'ADN microbien mais aussi, parfois, l'ADN du soi. Il apparaît donc comme un élément déterminant de la survie et la différenciation des lymphocytes B. Après micro-dissection laser des lymphocytes B des glandes salivaires, une analyse par RT-PCR quantitative a montré que les lymphocytes B transitionnels expriment fortement l'ARNm de TLR9 contrairement à ceux des centres germinatifs. Des lymphocytes B de donneurs sains ont été triés par cytométrie en flux puis stimulés in vitro par leur TLR9. Il s’ensuit une survie, une activation et une prolifération associées à des modifications phénotypiques. Les lymphocytes B transitionnels présentent des caractéristiques de la zone marginale, tandis que les lymphocytes B matures expriment des spécificités folliculaires des centres germinatifs. Enfin, des IgM et des IgG sont sécrétées par les deux types de population, mais avec une production d'auto-anticorps plus élevée issue de la différenciation des lymphocytes B transitionnels. L’expression accrue de TLR9 par les lymphocytes B transitionnels suggère qu'ils pourraient être particulièrement sensibles à une différenciation en cellules sécrétrices d'auto-anticorps par une maturation vers la zone marginale au sein des glandes salivaires. Le TLR9 pourrait bien devenir la cible des futures biothérapies.

Oral Communication presented at the ";Forum des Jeunes Chercheurs";, Brest (France) 2011.

International audience; OBJECTIVES: To assess the efficacy of the anti-CD20 antibody rituximab in improving physical function and health-related quality of life (HRQoL) in patients with active primary Sjögren's syndrome (pSS), as well as the duration and sources of HRQoL improvements. METHODS: Sixteen patients with pSS received rituximab infusions (375 mg/m2) at weeks 0 and 1 and were followed up for 36 weeks. All patients fulfilled 2002 American-European Consensus Group criteria for pSS and had active disease defined as scores >50 mm on two of four 100-mm visual analogue scales (VAS) evaluating global disease activity, fatigue, pain, and dryness. Standardised evaluations including the Short Form 36 Health Survey (SF-36) were conducted. SF-36 score changes from baseline to weeks 12, 24, and 36 were assessed. RESULTS: Baseline mean SF-36 scores were considerably decreased, compared to the general same-age population. Role-physical (14.1 ± 27.4), role-emotional (12.5 ± 29.9), vitality (26.2 ± 14.3), and general health (32.6 ± 11.2) were the dimensions with the worst scores. Twelve weeks after rituximab, the mental component summary score was improved in 15 patients (mean improvement, 31.2 ± 36.4, p=0.001) and the physical component summary score in 14 patients (mean improvement, 16.9 ± 26.2, p=0.049). Further improvements occurred from week 12 to week 24, and most of the gains were sustained at week 36. Improvements in the physical and mental component summary scores failed to correlate with improvements in the VAS scores. CONCLUSIONS: Substantial alterations in HRQoL were noted in patients with pSS. Rituximab infusions without corticosteroid therapy produced meaningful improvements in HRQoL. Controlled studies of rituximab are needed.

During the 10th International Symposium on Sjögren's Syndrome held in Brest, France, from October 1-3, 2009 (http://www.sjogrensymposium-brest2009.org), the creation of an international epigenetic autoimmune group has been proposed to establish gold standards and to launch collaborative studies. During this "epigenetics session", leading experts in the field presented and discussed the most recent developments of this topic in Sjögren's Syndrome research. The "Brest epigenetic task force" was born and has scheduled a meeting in Ljubljana, Slovenia during the 7th Autoimmunity congress in May 2010.The following is a report of that session. © 2010 Elsevier B.V.

BACKGROUND: The mechanisms involved in the pathogenesis of coronary artery ectasia (CAE) have not been elucidated. Circulating antiendothelial cell antibodies (AECA) are often detectable in systemic vasculitis and have been implicated in the pathogenesis of endothelial injury. Their prevalence in CAE is not known. METHODS AND Results: Out of 475 consecutive patients subjected to coronary angiography, 27 patients were diagnosed with CAE. Thirty patients matched for age, body mass index, sex, and coronary artery disease prevalence, served as controls. Serum AECA of IgG, IgM, and IgA isotypes were detected using a cell-based enzyme-linked immunosorbent assay (ELISA). Antinuclear antibodies (ANA) and antineutrophil cytoplasmic antibodies (ANCA) were detected using indirect immunofluorescence. IgG and IgM anticardiolipin antibodies (aCL) were detected using commercial ELISA. The prevalence of ANA and ANCA was similar in CAE patients and controls (33.3 vs. 43.3%, and 3.3 vs. 7.4%, respectively). There was no significant difference in IgG or IgM aCL reactivity between patients and controls. Both CAE patients and controls were negative for IgG AECA. The frequency of IgM AECA positivity was similar in CAE patients and controls. The prevalence of AECA of the IgA isotype was significantly higher in CAE patients (37.0 vs. 10%, P

Anti-Fc gamma receptor IIIb (Fc gammaRIIIb) human autoantibodies (Ab) have been classified previously into three groups, based on the results of an indirect immunofluorescence (IIF) test and an enzyme-linked immunosorbent assay (ELISA): IIF+/ELISA+ (group A), IIF+/ELISA- (group B), and IIF-/ELISA+ (group C) sera. In this study, differential effects between IIF+ autoAb, recognizing cell-bound Fc gammaR, and those ELISA+, recognizing only cell-free Fc gammaR, were studied on polymorphonuclear neutrophils (PMN). Neither group A nor B autoAb was cytotoxic, although both prolonged the survival of PMN by delaying spontaneous apoptosis. By the same extent, the PMN-binding antisera stimulated the appearance of a CD11b(dim) population, following a 12-h incubation. This event was associated with a lowered expression of beta2 integrin molecules, resulting in altered PMN function. Treatment with groups A and B autoAb reduced adhesiveness and respiratory burst. This impairment of the responses was more pronounced when the cells originated from donors NA1+ NA1+ rather than donors NA2+ NA2+. From our observations, the influences of anti-Fc gammaRIIIb autoAb on PMN survival, as well as function and subsequent dysregulation of the inflammatory response, have proven somewhat dependent on their target antigens, as determined by IIF coupled with ELISA and Fc gammaRIIIb polymorphism.

Some gammadelta T cells express a receptor for the Fc portion of immunoglobulin G (FcgammaRIII - CD16). The relevance of this Fc receptor to gammadelta T-cell function is at present unclear. Our previous studies have shown that gammadelta T cells express activation markers in patients with rheumatoid arthritis (RA). In this study we have examined the relative proportions of CD16+ gammadelta T cells in the blood and synovial fluid of these patients compared with control blood. CD16+ gammadelta T cells from RA patients were significantly reduced in synovial fluid compared with the circulation. That this was due to blocking of antibody binding to CD16 was unlikely as treatment of blood gammadelta T cells with RA synovial fluid (known to contain immune complexes) failed to alter expression of CD16. Treatment of blood gammadelta T cells with phytohaemagglutinin in vitro, resulted in a time-dependent decrease in expression of CD16, with a concomitant increase in expression of human leucocyte antigen-DR, at the single cell level. We conclude that expression of CD16 by gammadelta T cells is lost in the synovial compartment as the result of activation.

CD45RO+ T cells are referred to as memory or helper-inducer while CD45RA+ T cells are regarded as naive or suppressor-inducer T cells. The former population predominates in the peripheral blood and even more in the synovial fluid of patients with rheumatoid arthritis, to the expense of the latter population. Within the CD45RB+ compartment, there appears to be more of the fully-differentiated than of the early-differentiated CD4+ T cells. In spite of the fact that these lymphocytes are close to undergoing apoptosis, this programmed cell death is inhibited in the rheumatoid synovium.

Ann Med Interne (Paris)

Twenty-three patients with the CREST (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasia) variant of progressive systemic sclerosis, were clinically, histopathologically and serologically examined for the presence of Sjogren's syndrome (SS). Fourteen were found to be positive. No significant difference could be demonstrated between them and the remaining 9. Characteristics of patients with CREST were compared with those of 29 randomly chosen patients with primary SS. Parotid gland enlargement was more frequently present (p less than 0.01) in the latter than in the former. Virtually no patients with CREST with SS had antibodies to Ro(SSA)/La(SSB). J Rheumatol