Open AccessLong‐term outcome in mixed connective tissue disease: Longitudinal clinical and serologic findings
Author(s) -
Burdt Mark A.,
Hoffman Robert W.,
Deutscher Susan L.,
Wang Grace S.,
Johnson Jane C.,
Sharp Gordon C.
Publication year - 1999
Publication title -
arthritis & rheumatism
Language(s) - English
Resource type - Journals
eISSN - 1529-0131
pISSN - 0004-3591
DOI - 10.1002/1529-0131(199905)42:5<899::aid-anr8>3.0.co;2-l
Subject(s) - autoantibody , medicine , mixed connective tissue disease , serology , immunology , connective tissue disease , small nuclear ribonucleoprotein , snrnp , epitope , pulmonary hypertension , autoimmune disease , ribonucleoprotein , antibody , pathology , rna , biology , biochemistry , gene
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.