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The protein abnormality could be either congenital or acquired by an injury such as a virus infection.To date there is no evidence which indicates that TG, TPO, or other proteins of the thyroid of a patient with autoimmunity are abnormal.The antigens involved may in fact include proteins encoded by plasmids present in the infection and autoimmune thyroid disease in a large prospective study of individuals developing AITD (217).In theory an initial response to one antigen might proceed by reacting to the other antigen, and thereby spread and augment the autoimmune process.It is these alterations that are most probably the ultimate cause of the increase in autoimmunity after pregnancy.

Damage to thyroid cells does indeed occur in viral thyroiditis, such as in association with mumps or in subacute thyroiditis of unknown cause, but autoantibodies appear only transiently at low titer, and progressive lesions of the thyroid do not usually occur (reviewed in 198, 199).For instance, in a recent study of an animal model of Graves’ disease, 5α-dihydrotestosterone was given to mice a week before immunization with TSH-R, and this reduced both the severity of the hyperthyroidism that developed and downregulated the Th1 response (211a).Another hypothetical reason for the unequal sex ratio is that skewed X chromosome inactivation could contribute through the failure of some autoantigens expressed on one X chromosome to be expressed at a critical point in the disease pathway.In this regard it is of interest that persistent, apparently benign virus infection of the thyroid can be induced in mice (220), and that infection of neonatal mice with reo virus induces a polyendocrine autoimmunity (Fig. These agents could work by liberating thyroid antigens.Virus infection might also augment autoimmunity by causing non-specific secretion of IL-2, or by inducing MHC class II expression on TEC.

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Minor allelic differences apparently do occur but attempts to associate thyroid disease with polymorphisms of the TPO and TSH-R genes have been unsuccessful.