HLA-DQB1 ASSOCIATIONS WITH ANTI-TOPOISOMERASE-1 ANTIBODIES IN PATIENTS WITH SYSTEMIC-SCLEROSIS AND THEIR 1ST DEGREE RELATIVES

The frequency and functional properties of anti-topoisomerase-1 antibo dies (ATA) have been studied in 58 systemic sclerosis (SSc) probands, 218 first degree relatives and 22 spouses. The dependence of ATA on th e presence of certain HIA-DRB1 and HIA-DQB1 alleles was examined. ATA were detected by immunodiffusion, by absorption or inhibition of topoi somerase-1 enzymic activity, by immunoblotting of a K562 cell extract and by immunoprecipitation of S-35 radiolabelled cell lines. HIA 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 rel atives with ATA had SSc. All eight individuals with ATA directly inhib ited topoisomerase-1 function. Four of the eight had limited skin dise ase and four had diffuse skin involvement. The seven who were genotype d had at least one HIA-DQB1 allele encoding for tyrosine at position 3 0 of the first domain. Therefore, ATA are not widely dispersed within families, but rather are only present in those with SSc, and certain g enetic requirements appear necessary for their generation.