APOPTOTIC CELL CLEARANCE IN SYSTEMIC LUPUS-ERYTHEMATOSUS - I - OPSONIZATION BY ANTIPHOSPHOLIPID ANTIBODIES

Objective. To verify whether antiphospholipid antibodies (aPL) recogni ze and opsonize apoptotic human cells. Methods. Apoptosis was induced via CD95 crosslinking or ultraviolet irradiation. IgG and anti-beta(2) -glycoprotein I (anti-beta(2)-GPI) antibodies were purified from patie nt sera by affinity chromatography. The aPL that bound to apoptotic ce lls were assessed by flow cytometry, and the subdomains recognized wer e identified by confocal microscopy. Human macrophages were derived fr om monocytes, and their ability to phagocytose H-3-labeled apoptotic b odies, whether opsonized or not opsonized by aPL, was assessed. Tumor necrosis factor alpha (TNF alpha) secretion was evaluated by enzyme-li nked immunosorbent assay. Results. The aPL, but not control Ig or Ig f rom aPL-negative patients, bound to apoptotic cells, but not to viable cells. Nuclear antigens mere not recognized. Opsonization of apoptoti c cells by aPL substantially enhanced recognition and binding bg scave nger macrophages, with massive TNF alpha secretion. Conclusion. Antiph ospholipid antibodies facilitate apoptotic cell clearance by macrophag es and trigger TNF alpha release, possibly enhancing the immunogenicit y of the autoantigens they contain.