Autoantibody recognition of distinctly modified forms of the U1-70-kd antigen is associated with different clinical disease manifestations

Objective. To examine whether autoantibody recognition of modified forms of the U1-70-kd RNP antigen correlates with manifestations of rheumatic disea se. Methods. Blinded to clinical disease manifestations, sera from 27 rheumatic disease patients with U1-70-kd antibodies were used to immunoblot control, apoptotic, and oxidatively modified HeLa cell lysates. Using densitometry, recognition of antigen fragments was quantitated. The presence or absence of 1) lupus skin disease and 2) Raynaud's phenomenon (RP) was determined fo r each patient by chart review. The ability of patient sera to recognize th e different fragments was compared for patients with and without skin disea se and with and without RP. Results. Patients with lupus skin disease had higher recognition of apoptot ic U1-70 kd than did patients without skin disease (mean +/- SD fragment re cognition index [FRI] 1.35 +/- 0.57 versus 0.95 +/- 0.25; P < 0.024, by Stu dent's t-test). Patients with RP had higher recognition of oxidatively modi fied U1-70 kd than did patients without RP (mean +/- SD FRI 0.95 +/- 0.80 v ersus 0.24 +/- 0.22; P < 0.048). Conclusion. Recognition of apoptotically and oxidatively modified forms of the U1-70-kd autoantigen are associated with distinct clinical rheumatic di sease manifestations. This finding provides in vivo evidence for the hypoth esis that immune recognition of modified forms of self antigens may be rele vant to the pathogenesis of systemic rheumatic diseases. Understanding the antigenic modifications to which patients react may help predict the expres sion of rheumatic syndromes.