ANTICENTROMERE ANTIBODIES (ACA) IN SYSTEMIC-SCLEROSIS PATIENTS AND THEIR RELATIVES - A SEROLOGICAL AND HLA STUDY

Autoantibody reactivity to centromere proteins CENP-A, CENP-B and CENP -C was examined in 58 patients with systemic sclerosis (SSc), 218 firs t degree relatives and 22 spouses. HLA class II typing for HLA-DRB1 an d HLA-DQA1 was performed by restriction fragment length polymorphism ( RFLP) analysis in 50 families, and HLA-DRB1, HLA-DQA1 and HLA-DQB1 typ ing was performed by olignucleotide typing in 44 families. Eleven prob ands and two relatives had ACA. The two relatives with ACA also had SS c. One relative was an identical twin sister of a proband with ACA and the other relative was a sister of a proband with ACA. All ACA-positi ve probands and relatives were female, and all recognized CENP-A, CENP -B and CENP-C. The presence of at least one HLA-DQB1 allele not coding for leucine at position 26 of the first domain appeared necessary, al though not sufficient for the generation of ACA. Therefore within SSc families ACA is strongly associated with female gender and disease phe notype, and is at least in part genetically determined.