Autoimmune rheumatologic diseases
Clinical heterogeneity in systemic lupus erythematosus (SLE) is influenced by genetic and non-genetic susceptibility that drive disease expression and severity. The immune pathways that contribute to heightened disease activity in lupus by race are critical to understanding SLE disease mechanisms and outcomes. To assess this, whole blood samples (n=58) of European (EA) or African American (AA) controls and SLE patients with either high (SLEDAI≥4) or low (SLEDAIlo) and double negative B cells (CD27-IgD-), while AA patients with high disease activity had elevated frequencies of memory B cells (CD27+IgD-CD38+). African Americans exhibited greater dysregulation of phospho-signaling pathways following IFNα, TLR4, TLR7/8 and TLR9 pathways with a reduced ability to activate pERK, p38, pSTAT3 and pSTAT5 compared to low disease activity patients and controls, partly contributed by higher basal levels of activation. Further, AA patients with high disease activity had significantly elevated cytokine production at baseline compared to controls, low disease activity patients and EA SLE patients that included BLyS, IL-12p70, GM-CSF and TNFα. Our results support a model where race influences heightened SLE disease activity mechanisms with alterations in B cell signaling, and greater dysregulation in phospho-signaling and pro-inflammatory soluble mediators observed in AA patients.