THU0338 THE CIRCULATING CD19-POSITIVE LYMPHOCYTES IN PATIENTS WITH SYSTEMIC SCLEROSIS: MODULATION WITHIN A YEAR AFTER THE INITIATION OF RITUXIMAB THERAPY
Authors: L. P. Ananyeva, L. Garzanova, O. Koneva, M. Starovoytova, O. Desinova, O. Ovsyannikova, M. Cherkasova, A. Aleksankin
Journal: Annals of the Rheumatic Diseases (2020)

Background: Significant disorders of B-cell homeostasis have been detected in systemic sclerosis (SSc) [1,2]. The improvement of the disease with anti-CD20 monoclonal antibody rituximab (RTM) has been shown in SSc [3]. There are limited data on change in circulating B lymphocytes count after RTM treatment in patients with SSc. Objectives: to investigate the modulations in absolute and relative numbers of circulating CD19-positive B lymphocytes (B-lymph) in patients with SSc within a year after the initiation of RTM therapy. Methods: 71 pts with SSc were included in the prospective study. Mean age was 46±13 yrs., 83% were women, 59% had diffuse subset. Duration of SSC from the first non-Raynaud`s symptom was 5.6 ± 4.4 yrs. All pts received low doses of glucocorticoids and 45% -immunosuppressive medications. The average follow-up of patients was 13.2 ± 2.0 (11-18) months. The mean dose of RTM for the period of follow up was 1.43 ± 0.60 grams, 48 patients received &lt; 2 g of RTM (group 1, mean of 1.1 ± 0.1 g) and 23 patients received ≥ 2 grams of RTM (group 2, mean dose of 2.2 ± 0.6 g). Peripheral blood CD19-positive cell count was obtained by flow cytometry in patients and in 20 healthy persons, comparable in sex and age. Data are presented as the percentage (P %) and absolute number (AN) of B-lymph per ml of blood. In patients, the number of B-lymph was determined before (n=67 pts), within first month after the first introduction of RTM (n=66), 6 months later (n=34) and at the end of the study (n=71) Results: At baseline, the AN and P% of B-lymph in pts did not differ from the healthy control. In pts with short disease duration (≤ 3 yrs.) the number of B-lymph before treatment with RTM was the higher (compared with longer duration &gt; 3 yrs) those who was ill ≥3 yrs.) and there was negative correlation between B-lymph count and duration of the disease (R - 0.36, p=0.003 for AN and R - 0.48, p=0.001 for P %). The number of B-lymph was significantly lower in patients receiving cyclophosphamide (Cyc) before being started with RTM. There was a negative correlation between the AN of B-lymph and the cumulative dose of Cyc (R -0.293, p=0.016). In 1 month after the initiation of RTM a complete depletion of B-lymph was observed in all pts and in six months it persisted in 79% of cases, the rest began to repopulate (15%) or reached a normal levels (6%). At the end of the follow up the number of B-lymph was significantly lower than before treatment and a complete (n=41 pts) or partial (n=23) depletion of B-lymph remained, and only in 7 (10%) pts the count of this cells was normalized. We revealed a negative correlation between the AN of B-lymph and the cumulative dose of RTM (R-0.237, p=0.048). Higher doses of RTM in group 2 induced a more significant depletion than in group 1. Change in forced vital capacity and diffusing capacity of the lung (% predicted) during follow up were less pronounced for pts in group 1 compared with group 2 (ΔFVC 2,4% and 7,5% p=0,01; ΔDLCO -0,35% and 5,05%, p=0,001, respectively). Conclusion: RTM may be more effective at the early stage of the disease, when the level of B-lymph is the highest. In SSc, the repopulation of B-lymph after depletion with RTM develops slowly. There were a more significant depletion of B-lymph and a more pronounced improvement in pulmonary function with the higher dose of RTM to compare with the lower one. This results indicate the option of a flexible dosing regimen of RTM. References: [1]Sanges S. et al. La Revue de médecine interne 38 (2017) 113–124 [2]Forestier A. et al. Autoimmunity Reviews 17 (2018) 244–255 [3]Jordan S, et al. Ann Rheum Dis 2015;74:1188–1194. doi: 10.1136/annrheumdis-2013-204522 Disclosure of Interests: None declared