U1—70‐kd autoantibody–positive mixed connective tissue disease in children. A longitudinal clinical and serologic analysis

Abstract

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

T Cell Immunity in Connective Tissue Disease Patients Targets the RNA Binding Domain of the U1-70kDa Small Nuclear Ribonucleoprotein

“…Sera from patients seen in the Division of Immunology and Rheumatology at the University of Missouri (Columbia, MO) were characterized for the presence of autoantibodies reactive with the U1-70kDa polypeptide using immunodiffusion, immunoblotting, and ELISA as previously described (17,18). Sera were also characterized for reactivity with U1-RNA using an assay for binding to radioactively labeled U1-RNA, as described previously (19).…”

Clinical Course, Prognosis, and Causes of Death in Mixed Connective Tissue Disease

“…Organ involvement is often more extensive than was previously thought; neurological expression and pulmonary disease, erosive arthritis, various skin signs, and vasculitis have been added to the clinical picture 3,4,5,6,7,8,9,10,11,12,13,14,15 . Organ involvement is often more extensive than was previously thought; neurological expression and pulmonary disease, erosive arthritis, various skin signs, and vasculitis have been added to the clinical picture 3,4,5,6,7,8,9,10,11,12,13,14,15 .…”

Increased Frequency of Mutations in the <i>hprt</i> Gene of T Cells Isolated from Patients with Anti-U1-70kD-Autoantibody-Positive Connective Tissue Disease

“…Sera from all patients were characterized for the presence o f autoantibodics reactive with 70kD, A, B'/B, and D polypeptides using an snRNP-polypeptidc-specific enzyme-linked immunosorbent assay, as described previously [3,8], Sera were analyzed by immunoblotting for reactivity with 70kD, A, C, B'/B, and D polypeptides. The sera were also tested by double immunodiffusion for autoantibodies to SS-A (Ro), SS-B (La).…”

“…PM-I (PM-Scl), and. Scl-70, by passive hemagglutination for autoantibodies to extractable nuclear antigen (ENA), and by Crithidia luciliae for autoantibodies to double-strand ed DNA, as described [8].…”