IMMUNOGENETIC ANALYSIS OF 5 FAMILIES WITH MULTICASE OCCURRENCE OF SCLERODERMA AND OR RELATED VARIANTS/

Objective. To investigate the relative contribution of the major histo compatibility (MHC) gene complex in the etiopathogenesis of familial s cleroderma and/or its variants, in 5 Australian families, each with 2 affected members. Methods. Affected individuals and consenting first d egree relatives were examined and had blood collected for histocompati bility leukocyte (HLA) class I, class ZI antigen, and complement C4 ty ping. An antinuclear (ANA) profile screen on each family member was pe rformed. Results. Family 1, had 2 affected siblings (scleroderma, CRES T), each anticentromere positive (>1/640 titer), with identical HLA ha plotypes. A brother, who was HLA identical to his affected sisters was clinically normal and ANA negative. In Family 2, there were no HLA ha plotype similarities between the 2 sisters affected with diffuse scler oderma. Both were ANA positive (>1/640). A 3rd sister was HLA identica l to the proband but was clinically normal and ANA negative. In Family 3, affected siblings (CREST, morphea) had identical HLA haplotypes. I n Family 4, both mother (CREST) and one of her 2 daughters (scleroderm a) had anticentromere antibodies (1/2560). The unaffected daughter, no t sharing either of her sister's haplotypes, was normal and ANA negati ve. In Family 5, 2 sisters (CREST, CREST) were HLA identical. Conclusi on. A female predominance in familial scleroderma was observed. There was no common HLA haplotype between different families affected with s cleroderma or its disease variants. Within families (except in one cas e, where the possibility of crossover exists or a question of paternit y) affected siblings shared both HLA haplotypes. The development of di sease was not totally accounted for by HLA genes, since family members with the same HLA haplotypes as the proband, were not affected. It ap pears that genes within the MHC complex are required but are not suffi cient for the development of systemic sclerosis.