OP0284 IMMUNOPHENOTYPIC CHARACTERIZATION OF PERIPHERAL BLOOD-DERIVED B LYMPHOCYTES OF PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS DURING B-CELL TARGETED THERAPY WITH ANTI-BLyS

Background Belimumab, the first biological drug approved for treatment of patients with Systemic Lupus Erythematosus (SLE), is a fully human IgG1λ monoclonal antibody directed against BlyS (B Lymphocyte Stimulator). BLyS inhibition associated reduction in circulating B subsets and short-lived plasmacells Objectives The aim this study was to characterize cell phenotype SLE at baseline after B-cell targeted therapy Belimumab cohort active patients. Methods Fifty-four diagnosed according 2012 SLICC criteria (49 females, mean age 40.6±13.2 years, disease duration 12.3±9.0 SLEDAI-2K 6.6±3.1) who received belimumab were enrolled. Phenotyping peripheral blood (PB)- derived lymphocytes (using as phenotypic markers IgD, CD27 CD38) performed six (T6) twelve (T12) months 38 patients, together expression BAFF BAFF- R by flow cytometry. Results In whole cohort, over time observed percentage CD19 pos [T0:11.1±6.1% vs T6:6.4±3.4%,p<0.01;T12:4.2±3.4%,p<0.01] naïve cells (IgD neg ) [T0:55.8±28.7% T6:34.9±22.2%,p<0.01;T12:30.0±19.4%;p=0.04] an increase switched memory )[T0:21.0±20.2% T6:37.5±21.4%,p<0.01;T12:42.2±21.%7,p=0.02] anti-BLyS. Moreover, IgD T6(p=0.01) observed. Conversely, BAFFR blood-derived remained unchanged during Stratifying based on severe (renal and/or neurological) mild (articular cutaneous) organ involvement, significant percentage[T0:10.7±4.6% 6:6.8±2.4%,p=0.03;T12:4.5±3.5%,p=0.03] cells[T0:61.0±24.6% T6:38.9±17.5%,p<0.01;T12:36.9±16.0%,p=0.03] found involvement both subgroups [(severe T0:24.1±25.0% T6:44.9±27.4%,p=0.01) (mild T0:18.9±18.3 T6:31.2±12.7%,p<0.01)]. Evaluating regarding response (based SLEDAI-2K), T6 group,[(responders T0:55.4±29.3 T6:32.3±19.9,p<0.01)(no responders T0:63.1±41.3% T6:41.4±33.5%,p=0.05)] cells[(responders T0:22.4±21.2% T6:39.6±19.4%,p<0.01)(no T0:20.6±26.1% T6:38.6±35.3%,p<0.05)], higher responder than no-responder group (22.4±21.2% 20.6±26.1%,p=0.02). ROC curve analysis subset [AUC(95% CIs):0.761:(0.566-0.957)p=0.023] identified cut-off 9.94% 6 months. having rate ≥9.94% [OR:4.5(95% CIs:0.9-17.2)]; presence anti-dsDNA antibodies baseline[OR:5.2(95%CIs:1.2-22.1)], achieved early within from initiation. Conclusion Anti significantly impacts composition subpopulations relation distinct involvement. immunological features are novel putative biomarkers anti-BLyS References [1]D. Ramsköld et al. alterations SLE. EBioMedicine. 2019 Feb;40:517-527. [2]S. Piantoni Characterization B- T-cell compartment related factors belonging TNF/TNFr superfamily clinically systemic lupus erythematosus: serum levels strongest predictor therapy. Front Pharmacol. 2021 May 21;12:666971. Disclosure Interests None declared