RT Journal Article
SR Electronic
T1 AB0146 DRUG DEPENDENT ALTERATIONS IN B-CELL REPERTOIRE IN SYSTEMIC LUPUS ERYTHEMATOSUS PATIENTS WITH LOW DISEASE ACTIVITY
JF Annals of the Rheumatic Diseases
JO Ann Rheum Dis
FD BMJ Publishing Group Ltd and European League Against Rheumatism
SP 1373
OP 1373
DO 10.1136/annrheumdis-2020-eular.4412
VO 79
IS Suppl 1
A1 Zenz, S.
A1 Dreo, B.
A1 Prietl, B.
A1 Kofler, S.
A1 Sourij, H.
A1 Lackner, A.
A1 D’orazio, M.
A1 Brickmann, K.
A1 Gretler, J.
A1 Fürst-Moazedi, F.
A1 Stradner, M.
A1 Graninger, W.
A1 Brezinsek, H. P.
YR 2020
UL http://ard.bmj.com/content/79/Suppl_1/1373.2.abstract
AB Background: B-cells play a major role in the pathogenesis and perpetuation of the immune response in systemic lupus erythematosus (SLE). So far, B-cell subtypes have been studied well, but the precise mechanisms of the B-cell alterations during disease activity and during remission, depending on different medication, are still unclear.Objectives: The aim of our study was to investigate the drug dependent alterations in the B-cell repertoire of SLE patients with low disease activity (SLEDAI – 2K ≤4).Methods: Peripheral blood samples from 39 patients suffering from SLE (mean±SD; age 43±13 years, 87.2% females, disease duration 11.1±7 years) were drawn over 2 years. All SLE patients were in remission or low disease activity (median±SE, SLEDAI of 2.0±1.5). B-cells were characterized using CD19, CD20, CD5, CD27 antibodies and were grouped in naïve (IgD+27-), non-switched memory (IgD+, CD27+), memory (IgD-, CD27+), B1 (CD5+27-) and MBL-like (CD5++) B-cells. A quantitative flow cytometric bead-based assay (QuantiBRITE PE kit from Becton Dickinson) was used for the estimation of CD19 antibodies bound per cell. Further, CD38 and CD86 antibodies were used to characterize the B-cell subsets. All cytometric measurements were performed using a standardized BD LSR Fortessa platform. After 3 years of follow-up, patients’ data about disease activity and current medication were obtained.Results: 22 SLE patients were treated with hydroxychloroquine (85.8%) and 19 patients received mycophenolate mofetil (MMF; n=14; 54.6%) or azathioprine (AZA; n= 5; 19.5 %). 5 patients were treated with other DMARDs. Independently of hydroxychloroquine and/or MMF, no significant differences were seen in naïve, non-switched memory, post-switched memory, plasma blasts, B1- or MBL-like B-cells. Patients treated with AZA had significantly lower naïve B-cells (mean±SD, 39.3±6.7vs. 73.1±19.3 %; p = 0.028), but had significantly higher IgD-post switched B-cells (31.2±9.1 vs.12.5 ±9.2 %; p = 0.028, respectively) compared with no AZA-treatment. Interestingly, activated B-cells (5.5±1.5 vs. 1.8±1.1%; p = 0.009) were significantly higher in AZA-treated. After 3 years of follow-up, almost all patients were in remission (median±SE, SLEDAI of 2.0±2.0), except of 3 patients with a SLEDAI of ≥ 6. Interestingly, those patients had at baseline, statistically higher naïve B-cells (p = 0.041) and lower B1-like B-cells (p =0.020) compared with patients with low disease activity.Conclusion: Our results suggest that independently of hydroxychloroquine and/or MMF treatment, all patients with low disease activity had similar normal B-cell subsets. Interestingly, in the small group of patients who were treated with AZA, a reduced regeneration of B-cells was shown. Patients with higher disease and high naïve B-cells showed an increased disease activity after three years.Acknowledgments: The research was performed in “CBmed” and funded by the Austrian Federal Government within the COMET K1 Centre Program, Land Steiermark and Land Wien.Disclosure of Interests: None declared