Immunoreactivity to Yersinia enterocolitica antigens in patients with autoimmune thyroid disease

Recent reports have suggested that Yersinia enterocolitica proteins encoded by a 72-kilobase virulence plasmid (known as release proteins and now identified as YOP2-5) are antigens recognized specifically by patients with Graves' disease and of potential etiological importance in this disorder. To examine this hypothesis, we evaluated immune responses to YOP in patients with autoimmune thyroid disease and in normal controls. Humoral responses to Yersinia were assessed using Western blots of crude Y. enterocolitica membrane proteins, Yersinia release proteins (YOP2-5), and human thyrocyte membranes. Twenty-four of 25 Graves' and 10 of 18 Hashimoto's patients showed reactivity with the release proteins, primarily the 67-, 46-, 36-, and 25-kilodalton bands. However, 17 of 24 normal subjects also demonstrated serological reactivity to the release proteins, and the pattern of reactivity of these sera was similar to that in the thyroid patients. No correlation was noted between serological reactivity to the release proteins and thyroid hormone levels. Patients and controls with serological reactivity to YOP also showed reactivity with Yersinia membranes. In addition to the serological studies, cellular immune responses were determined by peripheral blood mononuclear cell proliferation assays. Cellular reactivity to the release proteins was present in four of five Graves' and both Hashimoto's patients tested, but also in two of six nonthyroid illness patients with serological immunity to the release proteins. Intrathyroidal lymphocytes obtained from two Graves' patients demonstrated marked proliferation in response to the release proteins. These results indicate that there is no unique pattern of serological reactivity against Yersinia membranes or the release proteins in patients with autoimmune thyroid diseases and suggest that any causal relationship between Yersinia infection and Graves' disease may be related to T-cell immunity.