Infection and thyroid autoimmunity: A seroepidemiologic study of TPOaAb

Abstract

Infectious agents have been implicated as triggers of autoimmunity. Prospective epidemiologic studies of infection with specific pathogens and the subsequent elevation of specific autoantibodies are difficult and costly to conduct. As a result, a solid body of evidence regarding this theoretically intriguing connection remains to be accrued. We studied term sera from 1807 pregnancies in 1591 women for whom IgG status for cytomegalovirus, Epstein-Barr virus, herpes simplex virus type 1, herpes simplex virus type 2, and/or Toxoplasma gondii was available from prior analyses. We tested the sera (masked regarding infectious status) for autoantibodies to thyroid peroxidase (TPOaAb) and then unmasked and linked them. Adjusted for other cofactors, prior infection with T. gondii was associated significantly with the elevation of TPOaAb, whereas seropositivity for other infections was not. Negative and positive findings for suspected triggers of autoimmunity should be reported to build the evidentiary basis needed to advance our understanding of the disease process. The positive association observed between prior infection with T. gondii and the elevation of TPOaAb is supported by an almost simultaneous study. These findings require further investigation. We believe that if T. gondii is in fact confirmed to trigger or enhance a TPOaAb response, the most likely mechanism involved is the bystander effect.

Prevalence of anti-toxoplasma antibodies in patients with autoimmune diseases

“…This is well supported by the observation that ATxA from healthy individuals cross-react with malignant cervical tissue antigens [34]. Second, an association between ATxAeIgG antibodies and antithyorid antibodies (TPOAb) was observed in sera from 1591 pregnant women [21]. Thus supporting, along with our data on AITD, the hypothesis that Toxoplasma can initiate a pathogenic process that may eventually result in clinically overt autoimmunity.…”

“…The present data support this view of APS pathogenesis by demonstrating an ATxA association with aPL antibodies and the anti-phospholipids syndrome. Third, we may hypothesize that T. gondii infection induces a bystander effect via activation of toll-like receptors (TLR) [21], as previously demonstrated for multiple TLR [35], and may thus lead to the expansion of autoantibodies under aberrant conditions (e.g., excessive and/or chronic TLR activation) [21,36].…”

“…Previous case reports and case-control studies have linked ATxA with polymyositis [16], rheumatoid arthritis (RA) [17e19], autoimmune thyroid diseases [20,21], Crohn's disease [22], anti phospholipid syndrome [23], Wegener's granulomatosis [24] and autoimmune bullous diseases [25]. While ATxA have been previously associated with SLE [26], subsequent studies challenged this association [27,28].…”

Graves' Disease Associated with Infectious Mononucleosis due to Primary Epstein-Barr Virus Infection: Report of 3 Cases

“…This report is the first to demonstrate the link between EBV infection and Graves' disease. On the other hand, it has been suggested that no differences were observed between patients with Graves' disease and controls in the prevalence of IgG antibodies against EBV (25,26). The role of EBV infection in the pathogenesis of Graves' disease has is not been fully elucidated.…”

T. gondii Infection Acquired during Pregnancy and/or after Birth may be Responsible for Development of both Type 1 and 2 Diabetes Mellitus

“…A possible role of microchimerism in the pathogenesis of some autoimmune diseases has been suggested because microchimeric cells may differentiate into many lineages in various tissues finally inducing diverse pathophysiologic processes during the host lifetime [276] (Table 4). For example, proliferation of these cells in maternal tissue environment may be at least in part responsible for development of autoimmune thyroid diseases because of a significant prevalence of anti-IgG T. gondii antibodies present in those individuals [25,277,278], as well as papillary thyroid cancer induction [279]. Fetal microchimerism may take place during pregnancy starting from the 4 th to 6 th week of gestation [280].…”