Autoantibodies to fibrillin 1 in systemic sclerosis - Ethnic differences in antigen recognition and lack of correlation specific clinical features orHLA alleles

Citation
Fk. Tan et al., Autoantibodies to fibrillin 1 in systemic sclerosis - Ethnic differences in antigen recognition and lack of correlation specific clinical features orHLA alleles, ARTH RHEUM, 43(11), 2000, pp. 2464-2471
Citations number
29
Categorie Soggetti
Rheumatology,"da verificare
Journal title
ARTHRITIS AND RHEUMATISM
ISSN journal
00043591 → ACNP
Volume
43
Issue
11
Year of publication
2000
Pages
2464 - 2471
Database
ISI
SICI code
0004-3591(200011)43:11<2464:ATF1IS>2.0.ZU;2-V
Abstract
Objective, We previously reported the presence of autoantibodies to the ext racellular matrix protein, fibrillin 1, in sera from patients with systemic sclerosis (SSc), These autoantibodies appeared to be highly disease-specif ic but had significantly different frequencies among ethnic groups. The aim s of this study were 3-fold: 1) to determine whether sera from SSc patients of different ethnic backgrounds recognized different antigenic epitopes of fibrillin 1, 2) to determine whether sera from patients with polymyositis/ dermatomyositis (PM/DM) with or without interstitial lung disease (ILD) als o produced these antibodies, and 3) to determine any correlation of anti-fi brillin 1 antibodies with specific clinical features of SSc, other autoanti bodies, or HLA class II alleles in a prospectively studied cohort of SSc pa tients with early (<5 years' duration) disease (the Genetics versus Environ ment In Scleroderma Outcome Study [GENISOS] cohort). Methods, Three recombinant peptides accounting for the N-terminal end, prol ine-rich C region, and epidermal growth factor-like calcium-binding (EGF-cb ) domains of fibrillin 1 were used in a radioimmunoassay to screen sera fro m a large group of SSc and PM/DM patients and ethnically matched controls. Results, The majority of Choctaw American Indians, Japanese, and African Am ericans with SSc produced IgM and/or IgG autoantibodies to one or more reco mbinant fibrillin 1 proteins, while <50% of Caucasians with SSc showed sero reactivity, There were striking ethnic differences in fibrillin 1 antigenic epitope recognition among these ethnic groups. African American SSc sera r ecognized primarily the N-terminal end, and Caucasian sera mostly recognize d the EGF-cb repeats and the proline-rich C region, in contrast, most Choct aw American Indian and Japanese SSc sera appeared to recognize 2 or 3 epito pes, respectively. PM/DM patient sera did not recognize any of the fibrilli n 1 epitopes regardless of the presence of ILD, In the prospective, multiet hnic GENISOS cohort, the presence of anti-fibrillin 1 antibodies did not co rrelate with any major clinical manifestations, other autoantibodies, or HL A class II alleles, Conclusion. There are striking ethnic differences in antigenic epitope spec ificity of anti-fibrillin 1 antibodies in pa(t)ients with SSc, and the majo rity of SSc patients, except for Caucasians, produce antibodies to fibrilli n 1, The antifibrillin response thus far remains specific for scleroderma s yndromes, but it does not correlate with any major clinical features, other autoantibodies, or HLA class II alleles.