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Background: Role of B- and T- lymphocytes is well established in pathogenesis of rheumatoid arthritis (RA). Self-containing activation of B-cells in ectopic germinative centers is followed by auto-activation of T-lymphocytes while T-cells themselves are antigen-presenting cells for B-lymphocytes [1-2]. As these processes continue with the duration of RA, different subsets of B- and T-cell might be prevalent at different stages of RA.
Objectives: Evaluate differences in dynamics of B- and T- cell subsets in early and progressed RA.
Methods: 53 patients with diagnosed RA(ACR/EULAR 2010 criteria) were included in research in October 2019 - May 2020. Age median 54,2 [47; 62] yrs. 2 groups were formed: 1st (n = 27 pts., 25 female and 2 male) with early arthritis, median duration of RA 6 [5; 12] months prior to therapy, mediane DAS28-CRP - 5,8 [5,15-6,2]; and 2nd group (n=26 pts., 22 female and 4 male) - patients with progressed RA, duration of RA 84 [24; 121] months, on DMARDs (methotrexate 20 [15; 20] mg/week or leflunomide 20 mg/day), mediane DAS28-CRP - 6,31 [5,64-6,88]. Control group included 29 individuals (23 female and 6 male), age median 58,5 [53; 62] yrs. Blood of all patients underwent standart flow cytometry with T- and B-cell immunotyping.
Results: B and C-cells subsets were studied. B-cells subsets are presented in
| B-cell subsets | 1 group (n=27) | 2 group (n=26) | Control group (n=29) | |||
| Cells, 10 9 /л | Persentage, % | Cells, 10 9 /л | Persentage, % | Cells, 10 9 /л | Persentage, % | |
| В-cell [CD19+] | 0,144 [0,1; 0,21] | 9,1 [7,5-10,9] | 0,105 [0,1-0,2] ** | 8,35 [6-10,2] | 0,2 [0,1–0,2] | 8,5 [7,2–11,0] |
| B-memory cell [CD19+CD27+] | 0,003 [0,00166; 0,0044] | 2,1 [1,6-3,1] | 0,0015 [0,001-0,003] * | 1,25 [0,9-1,7] *,** | 0,003 [0,001–0,007] | 2,2 [1,1–3,0] |
| Switched B-cells
| 0,0187 [0,0133-0,0289] | 16 [9,3-18,4] | 0,01 [0,005-0,02] | 6,8 [3,6-11,6] *,** | 0,02 [0,01–0,04] | 12,8 [9,3–17,0] |
| Non-switched B-cells [CD19+CD27+IgD+] | 0,0073 [0,00619-0,0122] | 5,9 [3,6-9,7] | 0,009 [0,006-0,01] | 7,45 [5,1-11,4]** | 0,01 [0,005–0,02] | 7,4 [3,7–11,1] |
| Double negative D-cells
| 0,021 [0,011-0,028] | 14 [9,6-19,5] | 0,02 [0,01-0,03] | 15,05 [11,9-18,1] | 0,02 [0,01–0,02] | 13,3 [7,1–19,3] |
| Naive B-cells
| 0,076 [0,063-0,13] | 61,6 [52,9-68,8] | 0,095 [0,07-0,1] | 70,85 [62,5-75,6] ** | 0,1 [0,06–0,1] | 64,7 [57,6–72,4] |
| Transitioning B-cells [CD19+CD38++CD10+IgD+CD27-] | 0,000424 [0,000162-0,000624]*,** | 0,2 [0,1-0,4] | 0 [0-0,0001] | 0 [0-0,1] | 0,0001 [0–0,0003] | 0,1 [0–0,1] |
| Plasmoblasts
| 0,00071 [0,00023-0,00129]*,** | 0,4 [0,3-0,8]*, ** | 0,0003 [0,00007-0,0004] | 0,15 [0,1-0,3] | 0,0002 [0,0001–0,0004] | 0,1 [0,1–0, 2] |
| Plasmocytes [CD19+CD38+] | 0,000262 [0,000106-0,000414]*, ** | 0,1 [0,1-0,3] | 0,0001 [0-0,0002] | 0,1 [0-0,1] | 0,0001 [0,00-0,0002] | 0,1 [0,05-0,1] |
Data presented as median and interquartile range. * - differences to control group were observed, p<0,05. ** - differences between pts.goups were observed, p<0,05. No significant difference between T-cell subsets was found. In comparison with healthy individuals, pts. with early RA had increased levels of switched B-memory cells, transitioning B-cells and plasmoblasts, the opposite was observed in progressed RA pts with addition of decrease in B-memory cells.
Conclusion: As disease activity was high in both groups, therefore therapy was ineffective, and results could be interpreted as natural progression of RA, resulting mainly in dynamics of switched B-memory cells, transitioning B-cells and plasmoblasts. These subsets might be indicating disease development patterns but further research is required.
REFERENCES:
[1]Weyand, C. M., &Goronzy, J. J. Ectopic germinal center formation in rheumatoid synovitis. Annals of the New York Academy of Sciences, 2003, 987, 140–149.
[2]Shi K., HayashidaK. Lymphoid Chemokine B Cell-Attracting Chemokine-1 (CXCL13) Is Expressed in Germinal Center of Ectopic Lymphoid Follicles Within the Synovium of Chronic Arthritis Patients. J Immunol 2001; 166:650-655.
Acknowledgments: The reported study was funded by RFBR, project 19-315-90090
Disclosure of Interests: None declared