Immunoglobulins of Patients Recovering fromYersinia enterocoliticaInfections Exhibit Graves' Disease-like Activity in Human Thyroid Membranes

Abstract

Substantial evidence suggests a link between infections with Yersinia enterocolitica (YE) and Graves' disease. We have now examined the sera of 72 patients recovering from YE infection for immunoglobulins that interacted with the TSH receptor in human thyroid membranes. Compared with controls, in concentrations between 1 and 4 mg/mL, patient IgG produced a significant, concentration-dependent inhibition of TSH binding (p less than 0.001) and stimulation of adenylate cyclase activity (p less than 0.005-0.05). Whereas IgG from normal individuals caused no stimulation of adenylate cyclase, IgG from controls caused some concentration-dependent displacement of TSH, as previously reported. However, IgG from convalescents of YE infections was significantly more potent than normal IgG in reducing the binding of TSH to the membrane. Thus, at each examined concentration, YE patients' IgG displaced more TSH than IgG from normal controls. For each milligram per milliliter increment of IgG in the assay, patients' IgG caused a 10.2% inhibition of TSH binding (r -0.90, p less than 0.001), significantly greater than that seen with normal IgG (p less than 0.02). The present studies provide the first demonstration that IgG of patients recovering from YE infections react with the human TSH receptor. The antibodies presumably are produced against the TSH-binding protein present in YE. However, in view of lack of evidence for thyroid dysfunction in the sera of patients recovering from yersiniosis and the presence of TSH-binding proteins in other bacteria, we postulate that infection with YE is neither necessary nor sufficient to cause thyroid autoimmune disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Has the Use of Antithyroid Drugs for Graves' Disease Become Obsolete?

“…Concepts of the pathogenesis of Graves' disease have in¬ cluded the notion that aberrant surface class II antigen (HLA-DR) on thyrocytes [or conceivably a viral or yersinial (55) infection] may serve to induce helper cells. Activated helper cells secrete interferon-7, which can then induce HLA-DR on thyrocytes.…”

Relationship Between Thyroid Autoimmunity and Yersinia Enterocolitica Antibodies

“…Some authors reported negative results regarding the seroreactivity in patients with AITD (11), but others found some relationship between anti Y. enterocolitica agglutinin antibodies and AITDs (3,4,6,7,9,10).…”

“…Y. enterocolitica antibodies can induce GD because of cross-reaction with the thyrotropin receptor. The development of GD has been documented in some cases recovering from previous Yersinia infection (7,10). For a precise confirmation, a prospective study after Yersinia infection is required.…”

“…Since then, several other groups pointed out the potential or possible etiologic importance of these bacterial antigens in the precipitation of autoimmune thyroid diseases (AITD) (4)(5)(6)(7)(8). AITD can coincide with a subclinical persisting infection of Y. enterocolitica, which is a frequent cause of enteric infection called yersiniosis (4,5,9).…”

“…Some authors claim that the majority of patients with GD who were found to be positive for thyroid receptor antibodies (TRAb), expressed antibodies against Y. enterocolitica in the form of IgG and IgA 6 weeks after the diagnosis (6). It has been shown that thyroid antibodies in patients with active yersiniosis exhibited a Graves' disease-like activity in human thyroid membranes, but thyroid dysfunction could not be demonstrated in these patients (7). It is known that Y. enterocolitica antigens that cross-react with human TSH, share multiple antigenic epitope with other bacterial antigens (e.g., Escherichia coli, mycoplasma) (11).…”