Antiantibodies to the extracellular matrix microfibrillar protein, fibrillin-1, in patients with scleroderma and other connective tissue diseases

Filemon K. Tan, Frank C. Arnett, Stephan Antohi, Shinichiro Saito, Adriana Mirarchi, Harry Spiera, Takeshi Sasaki, Ozaki Shoichi, Ken Takeuchi, Janadan P. Pandy, Richard M. Silver, Carwile LeRoy, Arnold E. Postlethwaite, Constantin A. Bona

    Research output: Contribution to journalArticlepeer-review

    107 Citations (Scopus)

    Abstract

    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 gone 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 antifibrillin-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 Sjogren'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.

    Original languageEnglish
    Pages (from-to)1066-1072
    Number of pages7
    JournalJournal of Immunology
    Volume163
    Issue number2
    Publication statusPublished - 1999 Jul 15

    ASJC Scopus subject areas

    • Immunology and Allergy
    • Immunology

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