CERTAIN individuals are more susceptible than others to many conditions. In recent years it has become clear that in rheumatic fever, susceptibility of the host is an important factor in the pathogenesis of the disease. It was concluded from genetic and epidemiologic studies that susceptibility to rheumatic fever is on a genetic and age basis. Although the susceptible child cannot be identified at the present time, the number of children expected to be susceptible in a group of families of known genotype may be determined on the basis of recessive inheritance. It may, therefore, be postulated that distributed among a group of families of known hereditary background are children who are susceptible and insusceptible to the acquisition of rheumatic fever.
As a direct result of long term observation of rheumatic families over a period of 30 years, a second generation of children of known hereditary background is available to us for exploratory studies. This group includes children from families in which one or both parents are rheumatic, or in which neither parent is rheumatic. In this group there are normal (insusceptible), susceptible and rheumatic children.
The nature of the hereditable factors which may be responsible for susceptibility is obscure. Recent advances in biochemical genetics have provocative implications in rheumatic fever. Of particular interest are the observations which demonstrate that such biochemical reactions as enzyme and protein specificities are gene determined.
As a working hypothesis it seemed reasonable to postulate that in a susceptible child, abnormal physiologic, chemical, immunologic or hormonal responses might be found.
Differences might then be observed in certain reactions between the normal group and a group containing a high proportion of genetically susceptible children.
This approach does not conflict with the concept that exogenous factors, irrespective of their nature, may also be operative. If the nature of the endogenous factors were known, the role of possible exogenous agents would be clarified.
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