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* Division of Rheumatology and Clinical Immunogenetics, Department of Internal Medicine, University of Texas Health Science Center, Houston, TX 77030;
Department of Microbiology, Mount Sinai Medical School, New York, NY 10029;
Second Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan;
Department of Medicine and Clinical Science, Kyoto University, Graduate School of Medicine, Kyoto, Japan;
¶ Department of Rheumatology, Juntenko School of Medicine, Tokyo, Japan;
|| Department of Immunology and Microbiology, Medical University of South Carolina, Charleston, SC 29425; and
# Division of Connective Tissue Diseases, University of Tennessee, Memphis, TN 38163
A duplication in the fibrillin-1 gene has been implicated as the cause of the tight skin 1 (tsk1) phenotype, an animal model of scleroderma or systemic sclerosis (SSc). In addition to the production of abnormal fibrillin-1 protein, the tsk1 mouse also produces autoantibodies to fibrillin-1. Among a population of Choctaw Native Americans with the highest prevalence of SSc yet described, a chromosome 15q haplotype containing the fibrillin-1 gene has been strongly associated with SSc. With a recombinant human fibrillin-1 protein, autoantibodies to fibrillin-1 were detected in the sera of Native American SSc patients that correlated significantly with disease. Abs to fibrillin-1 also were detected in sera from Japanese, Caucasian, and African-American SSc patients. Compared with other ethnic groups, Japanese and Native American SSc patients had significantly higher frequencies of anti-fibrillin-1 Abs. Sera from patients with diffuse SSc, calcinosis, Raynaud’s, esophageal dysmotility, sclerodactyly, and telangiectasias syndrome and mixed connective tissue disease also had significantly higher frequencies of anti-fibrillin-1 Abs than sera from controls or patients with other non-SSc connective tissue diseases (lupus, rheumatoid arthritis, and Sjögren’s syndrome). Ab specificity for fibrillin-1 was demonstrated by the lack of binding to a panel of other purified autoantigens. The results presented demonstrate for the first time the presence of high levels of anti-fibrillin-1 Abs in a significant portion of patients with SSc.
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