Red Blood Cell Groups and ABH Secretor System as Genetic Indicators of Susceptibility to Rheumatic Fever and Rheumatic Heart Disease

Abstract

Whereas the place of group A hemolytic streptococcal infection in the etiology of rheumatic fever has been demonstrated, the evidence for or against an underlying constitutional susceptibility, perhaps on a genetically determined basis and as an essential predisposing factor, is still controversial. The rapid progress made in recent years in immunogenetics and biochemical genetics has opened a new approach to the study of possible associations of genetically determined traits with disease susceptibility. An abundant literature has appeared attempting to establish associations between blood group types[long dash]particularly the ABO system[long dash]with disease. The present studies do not support the observations of the Taplow group and of others that the frequency of non-secretors among rheumatics is significantly greater than in non-rheumatics. The differences observed in the frequency of non-secretors of ABH substances are in the same direction but of lesser magnitude and not beyond the range of chance variation. With respect to other blood-group traits[long dash]specifically the ABO, Rh, MN, and Lutheran systems[long dash]the study population, the rheumatics and their non-rheumatic mates, is homogeneous. The frequency of ABH non-secretors among non-rheumatic population in the present study is higher than all normal study groups reported to date. In the light of this great variation in the normal, it becomes even more crucial that study populations be carefully matched against their controls to be certain that differences found are not mere reflections of this wide range. Differences in secretor status appear to be greater between the sexes in the propositi than between the propositi and their selected controls and than between the sexes among these controls. Since secretion is determined by auto-somal genes, these differences may be due to sampling variation, to other factors relevant to the various pathological aspects of rheumatic fever within our study group, or to factors not yet identified. This question will be considered in a subsequent report. On the basis of family studies in the present investigation, it is apparent that the presence of the non-secretor gene per se is not an essential requirement for susceptibility to rheumatic fever and/or rheumatic carditis. Among carefully evaluated rheumatic subjects, a sufficient number are homo-zygous secretors to refute the Glynn hypothesis in its present form.