A novel biomarker for a subset of human naïve B cells associated with autoimmunity 3128

Abstract Description Our previous studies demonstrated that constitutive expression of AT-rich interacting domain 3a (ARID3a), a DNA-binding protein, throughout B cell development resulted in autoimmune phenotypes in transgenic mice. Further studies revealed that ARID3a is over-expressed in B cells from patients with systemic lupus erythematosus compared to healthy control B cells. Increased numbers of total ARID3a+ SLE B cells were significantly associated with increased disease activity. Unexpectedly, ARID3a protein is evident in a subset of naïve B cells in SLE patients and in some other types of autoimmune disease while even ARID3a transcript is not observed in healthy naïve B cells. Our new in vitro studies indicate that ARID3a can be induced in a subset of healthy naïve B cells using stimuli associated with induction of double negative B cells shown to be expanded in lupus and associated with autoantibody production. Novel surface markers specifically associated with ARID3a expression in SLE naïve B cells have been identified by single cell RNA-seq and are also present in some other autoimmune conditions. Longitudinal studies to investigate if numbers of ARID3a+ naïve B cells predict upcoming flares in autoantibody production in SLE patients are in progress. In addition, new studies targeting ARID3a in vitro suggest that ARID3a is required for B cell activation. Together, these data implicate new therapeutic avenues for specifically eliminating those subsets of activated naïve B cells. Funding Sources NIH AI118836; DOD HT9425-23-1-0271, LR220036; University of Oklahoma Growth Fund Topic Categories Basic Autoimmunity (BA)