HLA-DQB1 associations with anti-topoisomerase-1 antibodies in patients with systemic sclerosis and their first degree relatives. United Kingdom Systemic Sclerosis Study Group.
The frequency and functional properties of anti-topoisomerase-1 antibodies (ATA) have been studied in 58 systemic sclerosis (SSc) probands, 218 first degree relatives and 22 spouses. The dependence of ATA on the presence of certain HLA-DRB1 and HLA-DQB1 alleles was examined. ATA were detected by immunodiffusion, by absorption or inhibition of topoisomerase-1 enzymic activity, by immunoblotting of a K562 cell extract and by immunoprecipitation of 35S radiolabelled cell lines. HLA class II typing for HLA-DRB1 and HLA-DQB1 was performed by oligonucleotide typing in 49 families. Six probands and two relatives had ATA. The relatives with ATA had SSc. All eight individuals with ATA directly inhibited topoisomerase-1 function. Four of the eight had limited skin disease and four had diffuse skin involvement. The seven who were genotyped had at least one HLA-DQB1 allele encoding for tyrosine at position 30 of the first domain. Therefore, ATA are not widely dispersed within families, but rather are only present in those with SSc, and certain genetic requirements appear necessary for their generation.
Whyte
J
J
Bath Institute for Rheumatic Diseases, UK.
Artlett
C
C
Harvey
G
G
Stephens
C O
CO
Welsh
K
K
Black
C
C
Maddison
P J
PJ
McHugh
N J
NJ
D000483:Alleles; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology*; D004264:DNA Topoisomerases, Type I / Q000276:immunology*; D004198:Disease Susceptibility / Q000276:immunology; D005802:Genes, MHC Class II; D020022:Genetic Predisposition to Disease; D006683:HLA-DQ Antigens / Q000235:genetics*; D059866:HLA-DQ beta-Chains; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D009679:Nuclear Family; D010290:Parents; D010375:Pedigree; D012426:Russia; D012595:Scleroderma, Systemic / Q000235:genetics / Q000276:immunology*; D014407:Tumor Cells, Cultured; D006113:United Kingdom
D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D004264:DNA Topoisomerases, Type I