NK cell phenotype and proliferation in Systemic Lupus Erythematosus

Abstract

Abstract Systemic Lupus Erythematosus (SLE) is a complex autoimmune disorder whose pathology appears to involve many immune cell types. While it is clear that autoantibody producing B cells as well as CD4+ T cell help are key contributors to disease, little is known regarding the role of innate lymphoid cells such as Natural Killer (NK) cells in the pathogenesis of SLE. We have characterized the phenotype of NK cells by multicolor flow cytometry in a large cohort of SLE patients. While the overall percentage of NK cells was similar or slightly decreased compared to healthy controls, a subset of patients displayed a high frequency of NK cells expressing the proliferation marker, Ki-67, which was not found in healthy donors. Only a moderate increase of Ki-67 was observed on other immune cell types such as total CD4+, CD8+ T cells or CD19+ B cells in the same donors. Increased NK cell proliferation was found to correlate with clinical parameters. Furthermore, proteomics analysis and auto-antibody arrays revealed significant correlations between NK cell expression of Ki-67 and specific serum protein biomarkers, as well as SLE associated auto-antibodies. These results will contribute to the understanding of the mechanistic role of NK cells in immune-mediated pathology of SLE.