Systemic lupus erythematosus (SLE) is a complex and multifactorial autoimmune disease with striking clinical, immunologic, and genetic heterogeneity, despite nearly ubiquitous antinuclear antibody (ANA) production. Multiple gene polymorphisms have been associated with the disease, but these individually account for only a very small percentage of overall SLE risk. In earlier studies, constitutive expression of the DNA-binding protein AT-rich-interactive domain 3A (ARID3a) in transgenic mouse B lymphocyte lineage cells led to spontaneous ANA production and preferential development of B cells associated with production of polyreactive antibodies. Therefore, we undertook this study to determine whether ARID3a was overexpressed in B lymphocytes of SLE patients and whether ARID3a expression was associated with disease severity.
A cross-section of SLE patients, rheumatoid arthritis patients, and age- and sex-matched controls was analyzed longitudinally for lupus disease activity, numbers of ARID3a+ peripheral blood mononuclear B cells from multiple B cell subsets, and immunoglobulin and cytokine levels.
Fifty of 115 SLE patients (43%) had dramatically increased numbers of ARID3a+ B cells compared to healthy controls. ARID3a was not expressed in naive B cells of healthy controls, but was abundant in these precursors of antibody-secreting cells in SLE patients. Total numbers of ARID3a+ B cells correlated with increased disease activity as defined by SLE Disease Activity Index scores in individuals assessed at 3 time points.
These findings identify B cell anomalies in SLE that allow stratification of patient samples based on ARID3a expression and implicate ARID3a as a potential marker of CD19+ B lymphocytes correlated with disease activity.