Proteins Phosphorylated during Stress-induced Apoptosis Are Common Targets for Autoantibody Production in Patients with Systemic Lupus Erythematosus

DOI PDF 被引用文献6件
  • Paul J. Utz
    From the *Division of  Tumor Immunology, the Dana Farber Cancer Institute; and the ‡Department of Medicine, Division of Rheumatology and Immunology, Brigham & Women's Hospital, Boston, Massachusetts 02115
  • Maria Hottelet
    From the *Division of  Tumor Immunology, the Dana Farber Cancer Institute; and the ‡Department of Medicine, Division of Rheumatology and Immunology, Brigham & Women's Hospital, Boston, Massachusetts 02115
  • Peter H. Schur
    From the *Division of  Tumor Immunology, the Dana Farber Cancer Institute; and the ‡Department of Medicine, Division of Rheumatology and Immunology, Brigham & Women's Hospital, Boston, Massachusetts 02115
  • Paul Anderson
    From the *Division of  Tumor Immunology, the Dana Farber Cancer Institute; and the ‡Department of Medicine, Division of Rheumatology and Immunology, Brigham & Women's Hospital, Boston, Massachusetts 02115

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<jats:p>Proteins cleaved by interleukin-1β converting enzyme family proteases during apoptosis are common targets for autoantibody production in patients with systemic lupus erythematosus (SLE). We have tested the possibility that proteins phosphorylated in cells undergoing apoptosis are also targets for autoantibody production in patients with autoimmune disease. Sera from 9/12 patients containing antinuclear antibodies (10/12 meeting diagnostic criteria for SLE or a lupus overlap syndrome), precipitated new phosphoproteins from lysates derived from Jurkat T cells treated with apoptotic stimuli (i.e., Fas-ligation, gamma irradiation, ultraviolet irradiation), but not with an activation (i.e., CD3-ligation) stimulus. Sera derived from individual patients precipitated different combinations of seven distinct serine-phosphorylated proteins. None of these phosphoproteins were included in precipitates prepared using sera from patients with diseases that are not associated with autoantibody production or using serum from rheumatoid arthritis patients. Protein phosphorylation precedes, or is coincident with, the induction of DNA fragmentation, and is not observed when apoptosis is inhibited by overexpression of bcl-2. Serum from four patients precipitated a serine/threonine kinase from apoptotic cell lysates that phosphorylates proteins of 23-, 34-, and 46-kD in in vitro kinase assays. Our results suggest that proteins phosphorylated during apoptosis may be preferred targets for autoantibody production in patients with SLE.</jats:p>

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