Long-term outcome in mixed connective tissue disease - Longitudinal clinical and serologic findings

Objective. To determine the long-term clinical and immunologic outcomes in a well-characterized cohort of 47 patients with mixed connective tissue dis ease (MCTD), including reactivity with U small nuclear RNP (snRNP) polypept ides. Methods. Patients were followed up over a period of 3-29 years with immunog enetic and systematic clinical and serologic analysis, Sera were analyzed f or reactivity with snRNP polypeptides U1-70 kd, A, C, B/B', and D, for anti -U1 RNA, and for anticardiolipin antibodies (aCL). Results, The typical core clinical features of MCTD tended to develop over time; features of inflammation as well as Raynaud's phenomenon and esophage al hypomotility diminished, while pulmonary hypertension, pulmonary dysfunc tion, and central nervous system disease persisted, following treatment. A favorable outcome was observed in 62% of patients; 38% had continued active disease or had died, with death associated with pulmonary hypertension and aCL, All patients had autoantibodies to the U1-70 kd polypeptide of snRNP, and most were positive for anti-U1 RNA, An orderly progression of intramol ecular spreading of autoantibody reactivity against snRNP polypeptides was observed, as was the novel finding of "epitope contraction" followed by dis appearance of anti-snRNP autoantibodies during prolonged remission, Conclusion, These patients demonstrated the typical immunogenetic, clinical , and serologic findings of MCTD, and the condition rarely evolved into sys temic lupus erythematosus or systemic sclerosis, The majority of patients h ad favorable outcomes,,vith pulmonary hypertension being the most frequent disease-associated cause of death. Intramolecular spreading of autoantibody reactivity against snRNP polypeptides,vas observed, followed by "epitope c ontraction" and ultimate disappearance of anti-snRNP autoantibodies during prolonged disease remission.