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

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.

Prevalence of scleroderma spectrum disorders in the general population of Estonia.

The purpose of this study was to estimate the prevalence of scleroderma spectrum disorders (SDS) in the general population of Estonia while taking into account environmental and ethnic factors. A random sample of 14,467 subjects from the general population were surveyed by mail questionnaire to detect those with suspected Raynaud phenomenon (RP) and SDS. A subsample of 2,154 participants was then seen during the field study to confirm the RP diagnosis and to perform a short clinical examination. Of 581 subjects with RP, 13 cases (all women) were diagnosed as having SDS; based on these findings, the estimated prevalence of SDS in the adult population is 228 per 100,000 (95% CL 121; 391), while in women alone it is 354 per 100,000 (95% CL 188; 605). The best estimate of SD (systemic scleroderma), based on ACR criteria, is 35 per 100,000 (95% CL 4; 127). No significant difference in SDS prevalence was found between the two environmentally different regions we studied. Although statistically not significant, the prevalence of SDS, especially of SD and CREST syndrome, among Russians was higher than among Estonians, as we had hypothesized. The distribution of SDS subtypes also suggests an ethnic difference. The overall prevalence of SD/CREST that we found is higher than that reported in studies not based on a random sample of the general population.