Cellular localization of nuclear antigen during neutrophil apoptosis: mechanism for autoantigen exposure?

Abstract

Juvenile-onset systemic lupus erythematosus (JSLE) is a multisystem autoimmune disease characterized by hyperactive B-cells producing auto-antibodies directed against nuclear antigens. A potential source of these antigenic components is apoptotic cells. We have previously demonstrated increased dysregulated neutrophil apoptosis in JSLE patients. Here we investigate autoantigen expression on JSLE neutrophils during apoptosis. Neutrophils from non-inflammatory controls and JSLE patients were incubated with JSLE and control serum. Apoptosis and dsDNA expression was measured using flow cytometry and confocal microscopy. Increased neutrophil apoptosis and dsDNA expression was observed in JSLE and control neutrophils incubated with JSLE serum. During neutrophil apoptosis nuclear material was exposed on the cell surface rather than within the cell as seen with viable neutrophils. The increased neutrophil apoptosis induced by JSLE compared with control serum resulted in increased surface expression of nuclear antigens. This may provide an additional mechanism leading to the generation of autoantibodies in JSLE.