Death, autoantigen modifications, and tolerance

Autoantibodies present in the serum of patients with a variety of inflammat ory diseases have proven useful as diagnostic markers and as probes with wh ich to elucidate biochemical and signaling pathways. The mechanisms governi ng the generation of autoantibodies remain elusive, constituting a critical missing link in our understanding of rheumatologic illnesses. Several line s of experimentation in recent years have strongly implicated events surrou nding cell death in this process. This review will address the potential ro le played by death-specific modifications of autoantigens in bypassing tole rance to highly conserved autoantigens, including nucleic acids, lipids, an d proteins.