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