Apoptotic cell clearance in systemic lupus erythematosus: I. Opsonization by antiphospholipid antibodies

Angelo A. Manfredi, Patrizia Rovere, Giacomo Galati, Silvia Heltai, Enrica Bozzolo, Laura Soldini, Jean Davoust, Genesio Balestrieri, Angela Tincani, Maria Grazia Sabbadini

Research output: Contribution to journalArticlepeer-review

Abstract

Objective. To verify whether antiphospholipid antibodies (aPL) recognize and opsonize apoptotic human cells. Methods. Apoptosis was induced via CD95 crosslinking or ultraviolet irradiation. IgG and anti-β2-glycoprotein I (anti-β2-GPI) antibodies were purified from patient sera by affinity chromatography. The aPL that bound to apoptotic cells were assessed by flow cytometry, and the subdomains recognized were identified by confocal microscopy. Human macrophages were derived from monocytes, and their ability to phagocytose 3H-labeled apoptotic bodies, whether opsonized or not opsonized by aPL, was assessed. Tumor necrosis factor a (TNFα) secretion was evaluated by enzyme-linked immunosorbent assay. Results. The aPL, but not control Ig or Ig from aPL-negative patients, bound to apoptotic cells, but not to viable cells. Nuclear antigens were not recognized. Opsonization of apoptotic cells by aPL substantially enhanced recognition and binding by scavenger macrophages, with massive TNFα secretion. Conclusion. Antiphospholipid antibodies facilitate apoptotic cell clearance by macrophages and trigger TNFα release, possibly enhancing the immunogenicity of the autoantigens they contain.

Original languageEnglish
Pages (from-to)205-214
Number of pages10
JournalArthritis and Rheumatism
Volume41
Issue number2
DOIs
Publication statusPublished - Feb 1998

ASJC Scopus subject areas

  • Immunology
  • Rheumatology

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