Objective. To determine the long-term clinical and immunologic outcomes in a well-characterized cohort of 47 patients with mixed connective tissue disease (MCTD), including reactivity with U small nuclear RNP (snRNP) polypeptides.Methods. Patients were followed up over a period of 3-29 years with immunogenetic and systematic clinical and serologic analysis. Sera were analyzed for 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 esophageal hypomotility diminished, while pulmonary hypertension, pulmonary dysfunction, 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 intramolecular spreading of autoantibody reactivity against snRNP polypeptides was observed, as was the novel finding of "epitope contraction" followed by disappearance 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 systemic lupus erythematosus or systemic sclerosis. The majority of patients had favorable outcomes, with pulmonary hypertension being the most frequent disease-associated cause of death. Intramolecular spreading of autoantibody reactivity against snRNP polypeptides was observed, followed by "epitope contraction" and ultimate disappearance of anti-snRNP autoantibodies during prolonged disease remission.

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Objective. To obtain longitudinal data on the clinical, serologic, and immunogenetic features of children with mixed connective tissue disease (MCTD).Methods. Eleven children with MCTD were followed up for a mean of 9.8 years. Enzyme-linked immunosorbent assay and immunoblotting were used to analyze sera for autoantibodies to small nuclear ribonucleoprotein polypeptides. HLA types were determined in 9 patients, by microcytotoxicity and DNA typing.Results. All 11 children had anti-U1-70-kd autoantibodies. Six of 9 were positive for HLA-DR2, 4 of 9 for HLA-DR4, and 9 of 9 for either HLA-DR2 or DR4. Outcomes were favorable with no functional impairment in 8 of the 11 children and were poor in 3.Conclusion. The frequency of HLA-DRZDR4 is increased among children with anti-U1-70-kd autoantibody positive MCTD.The long-term outcome in children with mixed connective tissue disease (MCTD) is unclear, with conflicting reports of both severely adverse as well as more favorable clinical outcomes described in the literature (1). Since the publication of earlier reports on MCTD in children, there have been substantial advances in the characterization of distinct autoantibodies against individual U small nuclear ribonucleoprotein ([UIsnRNP) polypeptides and in the characterization of HLA genotypes (2,3). In the present report, we present longitudinally obtained clinical, serologic, and immunogenetic data on children with MCTD who were examined at our institution during a 20-year period, and we correlate these findings with disease outcomes. PATIENTS AND METHODS Selection of patients.Records of all children seen in the Division of Immunology and Rheumatology at the University of Missouri Hospital and Clinics between 1969 and 1990 were reviewed by a physician. Patients selected for analysis were those who were under the age of 18 years at presentation to the Division of Immunology and Rheumatology, were found to have high-titer anti-RNP antibodies, and had overlapping clinical features of juvenile rheumatoid arthritis, systemic lupus erythematosus (SLE), dermatomyositis, or scleroderma, according to the criteria of Porter et a1 (4). Eleven patients who met these 3 criteria were identified for further study.Enzyme-linked immunosorbent assay (ELISA) and immunoblotting for antinuclear antibodies. Sera were characterized for the presence of autoantibodies reactive with