An immunogenetic study of the response to streptococcal
carbohydrate antigen of the cell wall was carried out on members of 15 multiplex families each having more than one sib affected with
rheumatic heart disease. They comprised 30 parents and 61 sibs (32 with
rheumatic disease and 29 without). Fifty healthy unrelated subjects served as controls. A history was taken and clinical examination carried out. Rheumatic activity was determined and HLA typing was carried out for nine A
antigens, 15 B
antigens, and six DR
antigens. The immune response of lymphocytes to streptococcal
polysaccharide antigen of the cell wall of group A beta haemolytic streptococci in vitro was studied by tritiated
thymidine uptake. The results were statistically and genetically analysed. It was found that (a) all subjects with
rheumatic disease were highly responsive to the streptococcal
polysaccharide antigen of the cell wall, the sib pairs being mostly HLA identical; (b) all low responders had no
rheumatic disease and their phenotypes were mostly different from those of the rheumatic member of their sib pair; (c) correlation of immune responsiveness (high or low) between HLA-identical sibs was significant, but insignificant between haplotype identical and non-identical sibs; (d) the gene responsible for high responsiveness to the streptococcal
polysaccharide antigen of the cell wall is recessive and closely linked to HLA. In conclusion, it was found that exposure to pharyngeal
infection with group A beta haemolytic streptococci may lead to
acute rheumatic fever in those with an inherited recessive gene responsible for high responsiveness to the streptococcal
polysaccharide antigen of the cell wall.