PROTEINS PHOSPHORYLATED DURING STRESS-INDUCED APOPTOSIS ARE COMMON TARGETS FOR AUTOANTIBODY PRODUCTION IN PATIENTS WITH SYSTEMIC LUPUS-ERYTHEMATOSUS

Proteins cleaved by interleukin-1 beta converting enzyme family protea ses 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 autoimm une disease. Sera from 9/12 patients containing antinuclear antibodies (10/12 meeting diagnostic criteria for SLE or a lupus overlap syndrom e), precipitated new phosphoproteins from lysates derived from Jurkat T cells treated with apoptotic stimuli (i.e., Fas-ligation, gamma irra diation, ultraviolet irradiation), but not with an activation (i.e., C DS-ligation) stimulus. Sera derived from individual patients precipita ted different combinations of seven distinct serine-phosphorylated pro teins. None of these phosphoproteins were included in precipitates pre pared using sera from patients with diseases that are not associated w ith autoantibody production or using serum from rheumatoid arthritis p atients. 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 precipi tated a serine/threonine kinase from apoptotic cell lysates that phosp horylates proteins of 23-, 34-, and 46-kD in in vitro kinase assays. O ur results suggest that proteins phosphorylated during apoptosis may b e preferred targets for autoantibody production in patients with SLE.