Apoptotic U1-70 kd is antigenically distinct from the intact form of the U1-70-kd molecule

Objective. To determine whether immune responses to an apoptotically modified form of a human lupus autoantigen can be distinguished from immune responses to the intact form of the same antigen. Methods. Inummoblot and enzyme-linked immunosorbent assay techniques were used to test human autoimmune sera for the presence of antibodies to apoptotic forms of the Ul-70-kd small nuclear RNP antigen, while antibody recognition of intact Ul-70 kd was blocked. Results. Apoptosis-specific Ul-70-kd antibodies were identified by immunoblot in 15 of 29 sera with antibodies to intact Ul-70 kd and in 2 of 25 sera without measurable antibodies to intact Ul-70 kd. Bacterially produced, purified, caspase-cleaved Ul-70 kd without additional posttranslational modifications was a target of apoptosis-specific antibodies in 3 of 9 Ul-70-kd-positive sera tested. Conclusion. The apoptotic form of Ul-70 kd displays B cell epitopes that are not displayed on the intact form of Ul-70 kd. Caspase cleavage in the absence of additional posttranslational modifications is sufficient to induce the display of some of these epitopes. Immunity to apoptotically modified proteins can develop against caspase-cleaved forms or against forms that undergo additional posttranslational modification.