Immunological landscape and B cell reactivity in lymph nodes of human SLE patients 3935

Abstract Description Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease marked by abnormal B and T cell reactivity against self-antigens, stemming from immune tolerance loss and sustained autoantibody production. However, the mechanisms behind tolerance breakdown and the roles of specific immune cells remain unclear due to limited access to human tissues. Recently, Lymph Node Fine Needle Aspirates (LN-FNAs) have become pivotal for studying tissue-resident immune cells, offering insights into their origins, phenotypes, and migration patterns. This is particularly relevant as innovative therapies, like CAR-T cell therapy, show promise in mitigating SLE symptoms. In this study, we profiled LN-resident immune cells from 40 SLE patients and 40 matched healthy controls using high-dimensional immunoprofiling, serological screenings, and tetramer-probe flow cytometry. We tracked Spike+ and Ro60+ B cells to assess foreign- and self-reactivity and traced their origins to germinal center (GC) or extrafollicular (EF) sites. Our findings reveal hyperactive immunity in SLE LNs, characterized by immune heterogeneity and expansions of plasma and/or GC cells, indicating distinct immune endotypes among donor groups. These patterns may also be shaped by lupus treatments. Ongoing single-cell analyses of EF and GC compartments aim to refine our understanding of SLE-associated immune endotypes, advancing therapeutic strategies and improving disease outcomes. Funding Sources U54-762 CA260563-01 Emory SeroNet and U19-AI110483 Emory Autoimmunity Center of Excellence. Topic Categories Basic Autoimmunity (BA)