LE cell phenomenon: nuclear IgG deposits inhibit enzymatic cleavage of the nucleus of damaged cells and support its phagocytic clearance by PMN

Abstract

Apoptotic cell death, phagocytic uptake, and their interplay may induce/trigger autoantibody production and autoimmunity. Herein the role of immunoglobulin G (IgG) anti-dsDNA autoantibodies in nucleo-phagocytosis by polymorpho-nuclear cells (PMN) has been analyzed. Necrotaxis, phagocytosis and PMN with engulfed nuclei can be imaged by vital microscopy. Vital microscopy revealed dead neutrophils with persistence of nuclei or ingested nuclei in 8/10 patients with lupus erythematosus (LE) and in 4/20 healthy controls ( P < 0.0006). The phagocytic clearance of dead cells/nuclei did not correspond to any of the analyzed apoptosis markers (annexin V, CD95, and active caspase 3). IgG staining of isolated PBMC nuclei as detected by flow cytometry was significantly higher in parallel to NUC+ ( P < 0.02). In vitro phagocytosis of substrates pre-treated with anti-dsDNA containing serum induced an increased phagocytic capacity as compared to normal serum. These data suggest that anti-dsDNA antibodies seem to inhibit enzymatic cleavage of nuclei from damaged cells, and improve their phagocytic uptake by PMN, which finally results in LE cell formation.