Genetic Basis of Spontaneous Autoimmune Thyroiditis

Abstract

Autoimmune diseases, both organ-specific and systemic, have a multifactorial basis with a definite genetic component. Most investigations on the theoretically and practically important problem of autoimmunity have focussed on the genetic basis of the aberrant immunological reactivity in experimental animals and man afflicted with autoimmune disease (for Review see 1,2). Much less emphasis has been given to the role of hormones as facultative factors modulating the development and severity of autoimmune diseases, reflected, e.g., by the preponderance of most - but not all - of these conditions in females^3,4. Our own group has advocated a role for genetically determined primary alterations of the target organ as an obligatory prerequisite for the emergence of spontaneous autoimmune thyroiditis (SAT) based on studies on the Obese strain (OS) of chickens. This new concept is schematically depicted in Figure 1 and has been presented in several recent reviews^5,6. As can be seen in Figure 1 both obligatory and facultative factors, the latter having a modulatory role only, contribute to the final outcome of a given autoimmune disease. The OS chickens, which spontaneously develop an autoimmune thyroiditis early in life that closely parallels human Hashimoto thyroiditis, are especially suited as an animal model for the study of the relative contributions of the different factors outlined in Figure 1. Chickens have several advantages over mammalian species for this kind of investigation: (a) the extramaternal development of the embryo, (b) large numbers of offspring can be obtained from each pair of parents, (c) the expression of major histocompatibility complex (MHC = B locus in the chicken) antigens on the surface of the nucleated erythrocytes which allows easy and efficient tissue typing, (d) the characteristic morphological dichotomy of the avian immune system, and (e) the availability of inbred and even congenic normal strains of chickens for crossbreeding and backcross experiments.