Anti-fibrillin-1 autoantibodies in systemic sclerosis are GM and KM allotype-restricted

GM and KM allotypes - genetic markers of immunoglobulin (Ig) gamma and kapp a chains, respectively - have been shown to play an important role in genet ic predisposition to some autoimmune diseases. To determine their role in s usceptibility to systemic sclerosis (SSc; scleroderma) and in the generatio n of anti-fibrillin-1 antibodies, 148 SSc patients and 191 controls were ty ped for several GM and KM allotypes by a standard hemagglutination inhibiti on method. IgG and IgM antibodies to fibrillin-1 were measured by radioimmu noassay. GM and KM phenotypes were not significantly associated with SSc. H owever, these determinants significantly influenced the production of anti- fibrillin-1 antibodies in SSc patients. In Caucasians, GM1,3,17 23 5,13,21 and GM3 23 5,13 phenotypes were associated with the presence and absence of IgG autoantibodies, respectively. The production of these autoantibodies w as also associated with KM allotypes, KM1,3 heterozygosity being associated with response and homozygosity for the KM3 allele with nonresponse to fibr illin-1. In African-Americans, the KM1 homozygotes were associated with the absence of anti-fibrillin-1 antibodies and the KM3 homozygotes with the pr esence of autoantibodies. In this ethnic group, the GM1,17 5,13 phenotype w as associated with the absence of IgM autoantibodies. This represents the f irst description of genetic control of autoimmunity to fibrillin-1 in scler oderma. Copyright (C) 2001 S. Karger AG, Basel.