ACTIVE LUPUS NEPHRITIS PATIENTS DISPLAY AN INCREASED PROPORTION OF RECENTLY ACTIVATED NAÏVE DNA-REACTIVE B CELLS

K. Wangriatisak, F. Faustini, R. Kumar, C. De Vries, P. Pisitkun, P. Chootong, V. Malmström, I. GunnarssonFaculty of Medical Technology, Mahidol University, Department of Clinical Microbiology and Applied Technology, Nakhonpathom, Thailand Karolinska Institutet, Department of Medicine, Division of Rheumatology, Stockholm, Sweden Karolinska University Hospital, Unit of Rheumatology, Stockholm, Sweden Karolinska Institutet, Center for Molecular Medicine, Stockholm, Sweden Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Department of Medicine, Division of Allergy, Immunology and Rheumatology, Bangkok, Thailand  Background Altered composition of B cell compartments is known in patients with systemic lupus erythematosus (SLE). However, similar characterisation of the disease-associated autoreactive B cells remains scarce. Elucidating the autoreactive B cell subsets and their association to lupus manifestations may provide tools for monitoring, biomarkers and even identifying possible targets for future therapeutic intervention. Objectives To investigate phenotypic characteristics of extrafollicular B cell subsets in a cohort of SLE patients. Methods Twelve SLE patients, including nine with positive anti-dsDNA antibodies (75%), and ten healthy controls (HCs) were recruited for this study. Data was represented as median and interquartile range (IQR). To identify DNA-reactive B cells, surrogate peptide (DWEYSVWLSN) that serves as dsDNA mimotope was used, as previously shown (1, 2). The phenotype of peripheral B cell subsets and DNA-reactive B cells was analyzed by spectral flow cytometric analysis. The correlations between different B cell populations and Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) scores, clinical manifestations and laboratory data were assessed. Results In SLE patients, median SLEDAI-2K score was 14.5 (4.5-19.5), median age and disease duration were 32 (29-48.5) and 10 (1-13) years, respectively. Eight patients presented with lupus nephritis (LN), with proliferative (class III/IV, n = 2), membranous (class V, n = 1) and mixed histological pattern (class III & V, n = 3 and class IV & V, n = 2). Phenotypic analysis showed an expansion of recently activated, so called activated naïve (aNAV: CD11cCXCR5CD21CD27IgD, p = 0.0005), double negative 2 B cells (DN2: CD11cCXCR5CD21CD27IgD, p = 0.0001) and double negative 3 B cells (DN3: CD11cCXCR5CD21CD27IgD, p = 0.005) in the blood of the total SLE patient group compared to HC, with aNAV B cells frequency being higher in LN patients (Figure 1). DNA-reactive B cells were mostly represented by an aNAV phenotype (CD11cCXCR5CD21) which overexpressed CD11c and CD80. Moreover, a significantly increased percentage of such autoreactive B cells was observed in LN patients (median (IQR) 0.13% (0.095-0.160) compared with non-LN patients (median (IQR) 0.056% (0.042-0.070), p = 0.0357). The percentage of aNAV B cells were positively correlated with disease activity measured as SLEDAI-2K index (r = 0.619, p = 0.036). These aNAV B cells also had a positive correlation with DN2 (r = 0.578, p = 0.049) and plasmablasts (r = 0.420, p = 0.041). Conclusion Our data show that aNAV B cells are expanded in SLE and display autoreactivity to dsDNA. The association between the frequency of aNAV B cells and disease activity, and with lupus nephritis suggests that these cells may be used as a monitoring biomarker in the disease. References Jacobi AM, Zhang J, Mackay M, Aranow C, Diamond B. Phenotypic characterization of autoreactive B cells--checkpoints of B cell tolerance in patients with systemic lupus erythematosus. PLoS One. 2009;4(6):e5776. Wangriatisak K, Thanadetsuntorn C, Krittayapoositpot T, et al. The expansion of activated naive DNA autoreactive B cells and its association with disease activity in systemic lupus erythematosus patients. Arthritis Res Ther 2021;23:179. Image/graph:Figure 1. Frequency of aNAV B cells in LN patients with different histological classes with respect to non LN and HC Disclosure of Interests None Declared. Keywords: Adaptive immunity, Kidneys, Systemic lupus erythematosus DOI: 10.1136/annrheumdis-2023-eular.5747Citation: , volume 82, supplement 1, year 2023, page 11Session: Adaptive immunity (T cells and B cells) in rheumatic diseases (Oral Presentations)