Author Interviews, Kidney Disease, Rheumatology / 24.01.2022

Stephen Connelly, PhD Co-founder & Chief Scientific Officer Equillium, Inc. San Diego, California  What is the background for this study?    Response: Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disease that predominantly affects women in the reproductive age range. Approximately 50% of SLE patients experience lupus nephritis (LN), a serious complication that is accompanied by significant morbidity and mortality. Progression of LN to chronic kidney disease is common, with 10% of patients with LN developing end-stage kidney disease. T cells, play a central role in the pathogenesis of both SLE and LN by mediating tissue damage and enhancing the production of autoantibodies by promoting B cell differentiation, proliferation, and maturation. These T cells express CD6, a costimulatory receptor that through its binding to activated leukocyte cell adhesion molecule (ALCAM), expressed on immune cells and tissues, modulates both the activity and trafficking of effector T cells (Teff). The expression of both CD6 and ALCAM (CD6-ALCAM pathway) have been associated with pathogenic effector T cell activity and trafficking in multiple autoimmune and inflammatory diseases. Based on a comprehensive screen of more than 1100 urine proteins, soluble urinary ALCAM (uALCAM) was identified as one of only a few molecules that were elevated in the urine of patients with SLE with active renal involvement compared with patients with quiescent or no prior nephritis. However, no studies had been conducted to characterize the cellular sources of the soluble ALCAM and questions remained about the relevance of this protein and whether it was associated with the pathology of the disease. (more…)