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SAT0284 Association of pathogenic and regulatory B-cell subsets with clinical and histological features in primary sjÖgren's syndrome
  1. F Carubbi1,2,
  2. A Alunno3,
  3. P Cipriani1,
  4. P Di Benedetto1,
  5. V Liakouli1,
  6. P Ruscitti1,
  7. O Berardicurti1,
  8. S Di Bartolomeo1,
  9. R Gerli3,
  10. R Giacomelli1
  1. 1Department of Biotechnological and Applied Clinical Science, Rheumatology Unit, School of Medicine, University of L'Aquila
  2. 2Department of Medicine, ASL1 Avezzano-Sulmona-L'Aquila, L'Aquila
  3. 3Department of Medicine, Rheumatology Unit, University of Perugia, Perugia, Italy

Abstract

Background Several data pointed out that B-cells play a central role in the development, maintenance and progression of primary Sjögren's syndrome (pSS). B-lymphocyte hyperactivity, salivary gland (SG) infiltration, and the development of B-cell follicles containing germinal center (GC)-like structures, represent hallmarks of the disease. On this basis, B-cell depleting therapy with anti-CD20 monoclonal antibody rituximab (RTX) has been employed in pSS showing promising results. However, currently available data do not allow to draw definitive conclusion on its efficacy.

Objectives Aim of the study was to assess mature and regulatory B cell subsets in patients with pSS and explore possible associations with clinical and histological features and their possible modulation by RTX treatment.

Methods We evaluated by flow cytometry peripheral blood (PB) B-cell subsets (mature B cells: Bm1, Bm2, Bm2', Bm3, Bm4, early(e)Bm5, Bm5; IL-10-producing B-cells), in 17 pSS patients and in 10 healthy donors (HD). Nine pSS patients received a course of RTX (1000 mg at days 1 and 15) and PB B-cell subsets were also evaluated after 3 (T3) and 6 (T6) months and compared to baseline values (T0).

Results We confirmed that the percentage of Bm1, eBm5 and Bm5 was lower and that of Bm2, Bm2' and Bm3+Bm4 was higher in pSS patients compared to HD (all p<0.05). When we divided patients according to the ESSDAI score (<5 or ≥5) or to SG-GC (presence/absence), we observed for the first time that the percentage of Bm2' cells, also called GC founders, was higher in patients with ESSDAI≥5 (p=0.02) compared to those with lower ESSDAI score and in pSS patients with GC (p=0.02) compared to those without GC. Although we observed a reduction of all B-cells subsets at T3 and T6 after RTX treatment, the proportion of Bm1, Bm3+Bm4, eBm5 and Bm5 persisted lower and the percentage of Bm2 and Bm2' persisted higher in pSS patients (p<0.05) compared to HD. No differences regarding IL-10-producing B-cells was obeserved between pSS patients and HD. However, the percentage of IL-10-producing B-cells was higher in patients with ESSDAI≥5 compared to patients with ESSDAI<5 (p=0.02).

Conclusions We demonstrated for the first time that a subset of circulating mature B-cells, Bm2', also called GC founders, is strongly associated with higher disease activity and with the presence of SG-GC. Moreover, a higher ESSDAI is associated with higher percentage of circulating IL-10-producing B-cells. Pathogenic B-cell hyperactivity is a hallmark of pSS, however B-cells are also a source of inhibitory cytokines such as IL-10 and TGF-beta and the increase of IL-10 producing B cells that we observed in active pSS patients may suggest an ongoing compensatory mechanism to counteract chronic inflammation. Therefore, the design of novel B cell targeted therapies should ensure that only pathogenic B cells are depleted and regulatory B cell subsets are not hampered while, ideally, potentiated.

References

  1. Binard A et al. Ann Rheum Dis 2009;68:1447–1452.

  2. Carubbi F et al. Arthritis Res Ther 2013;15:R172.

  3. Carubbi F et al. Lupus 2014; 23:1337–49.

  4. Kroese FG, et al. B-cell hyperactivity in primary Sjögren's syndrome. Expert Rev Clin Immunol. 2014;10:483–99.

References

Disclosure of Interest None declared

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