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OP0008 Peripheral Blood B Cell Subsets and BAFF/April Receptor Expression, Together with Circulating BAFF and April Levels, are Disturbed in Rheumatoid Arthritis but not in Ankylosing Spondylitis
  1. B. Gaugler1,
  2. C. Laheurte2,
  3. E. Bertolini3,
  4. D. Wendling3,
  5. P. Saas4,
  6. E. Toussirot2
  7. CBT-506
  1. 1INSERM UMR1098, Etablissement Français du Sang / Université de Franche Comté
  2. 2Clinical Investigation Center Biotherapy
  3. 3Rheumatology
  4. 4INSERM UMR1098, University Hospital, Besançon, France

Abstract

Background B cells play a critical role in systemic autoimmune disease and especially rheumatoid arthritis (RA). BAFF and APRIL are involved in B cell activation and survival. Few studies have evaluated the distribution of the different peripheral blood B cell subsets in RA as well as the expression of BAFF/APRIL receptors. Ankylosing spondylitis (AS) is an inflammatory rheumatic disease without current evident contribution of B cells to the inflammatory response.

Objectives to evaluate the distribution of circulating B cell subsets and the expression of BAFF/APRIL receptors (TACI, BCMA and BAFF-R) as well as the circulating levels of BAFF and APRIL in patients with RA or AS compared to healthy controls (HC).

Methods 59 patients with RA (ACR criteria, 12 M, age [mean ±SEM; years]: 58 ± 1.5, disease duration : 10.1 ± 1.5; all under traditional DMARDs, no biologics, corticosteroids < 10 mg/day N= 33), 61 patients with AS (modified NY criteria; 46 M; age : 46 ± 1.8, disease duration:11.6 ± 1.2; all under NSAIDs or traditional DMARDs) and 61 HC (13 M; age: 43.6 ± 1.8) were evaluated. For each subject, peripheral blood B cell subsets were assessed using multi-color flow cytometry. B cell subsets were analysed according CD27, CD38 and IgD staining (naive B cells: CD27- IgD+ CD38lo, transitional: CD27- IgDlo CD38hi, pre-GC: CD27+IgD+CD38hi, post-GC: CD27+IgD-CD38lo). The expression of BAFF-BR3, TACI and BCMA was analysed on each subset. RFI was calculated by dividing the MFI of the marker divided by MFI of the isotype-matched mAb. BAFF and APRIL serum levels were determined by ELISA using commercially available kits (Bender MedSystems and R&DSystems) respectively.

Results Circulating BAFF and APRIL levels were increased in RA compared to HC (1100.5 ± 62.5 vs 904.9 ± 29.4 pg/ml, p= 0.01 and 19116.3 ± 4918.6 vs 5699.2 ± 1034.5 pg/ml, p < 0.001, respectively), while no difference was observed in the levels of these activating B-cell factors in AS and HC. The ratio BAFF levels/peripheral B cell count was also significantly increased in RA (p = 0.04). The following B cell subsets were decreased in RA compared to HC: total B cells (p= 0.004), naïve B cells (p = 0.02), transitional B cells (p < 0.001), while post GC and CD27+ B cells were not different. B-cell subsets were comparable in AS and HC. Expression of BAFF and APRIL receptors were increased in the RA group, especially TACI on CD19+ B cells, transitional B cells and pre GC B-cells (all p < 0.05) and BCMA on CD19+, naive B cells, transitional B cells, memory B cells, pre-GC and post-GC B-cells (p < 0.05) while BAFF-R RFI was comparable in RA and HC. The expression of BAFF/APRIL receptors did not differ between AS and HC.

Conclusions Overall, our data confirm that B cell responses are altered in RA with biased repartition of B cell subsets, elevated levels of B cell activating cytokines and increased expression of their receptors. These results may be helpful for guiding and /or monitoring B cell targeted therapies in RA. In contrast, no alteration was observed in AS patients excluding an involvement of disturbed B cell responses in AS.

Disclosure of Interest None Declared

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