Fk. Tan et al., Autoantibodies to the extracellular matrix microfibrillar protein, fibrillin-1, in patients with scleroderma and other connective tissue diseases, J IMMUNOL, 163(2), 1999, pp. 1066-1072
A duplication in the fibrillin-1 gene has been implicated as the cause of t
he tight skin 1 (tsk1) phenotype, an animal model of scleroderma or systemi
c sclerosis (SSc), In addition to the production of abnormal fibrillin-1 pr
otein, the tsk1 mouse also produces autoantibodies to fibrillin-1. Among a
population of Choctaw Native Americans with the highest prevalence of SSc y
et described, a chromosome 15q haplotype containing the fibrillin-1 gene ha
s been strongly associated with SSc, With a recombinant human fibrillin-1 p
rotein, autoantibodies to fibrillin-1 were detected in the sera of Native A
merican SSc patients that correlated significantly with disease, Abs to fib
rillin-1 also mere detected in sera from Japanese, Caucasian, and African-A
merican SSc patients. Compared with other ethnic groups, Japanese and Nativ
e American SSc patients had significantly higher frequencies of antifibrill
in-1 Abs. Sera from patients with diffuse SSc, calcinosis, Raynaud's, esoph
ageal dysmotility, sclerodactyly, and telangiectasias syndrome and mixed co
nnective tissue disease also had significantly higher frequencies of anti-f
ibrillin-1 Abs than sera from controls or patients with other non-SSc conne
ctive 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.