CONTEXT: In addition to genetic susceptibility, Yersinia enterocolitica (YE) infection played an important causative role in the pathogenesis of Graves' disease (GD) through molecular mimicry. However, the specific YE proteins and epitopes recognized by anti-TSH receptor (TSHR) autoantibodies (TRAb) have not been fully clarified, resulting in conflicting results from clinical research. OBJECTIVE: Our aim was to explore the roles of YE in the pathogenesis of GD and identify the YE proteins and epitopes that are similar to the TSHR and are recognized by TRAb. DESIGN: Assays of YE antibodies, TRAb, thyroglobulin antibodies, and thyroid microsomal antibodies as well as cross-absorption and two-way immunodiffusion were performed in patients with GD. Using mass spectrometry and the bioinformatics tools of protein structure modeling and epitope prediction, we identified the YE protein and its epitope, which was recognized by TRAb and was similar to TSHR. RESULTS: Our study demonstrated for the first time that the YE protein outer membrane porin F protein (ompF) shared cross-immunogenicity with a leucine-rich domain of TSHR. The epitope recognized by antihuman TSHR antibody is located within the ompF region of amino acids 190-197, and the polyantibody against ompF protein showed TSAb activity. CONCLUSIONS: Our results suggest that YE ompF is involved in the production of TRAb and the pathogenesis of GD through molecular mimicry. These findings are potentially important for understanding the role molecular mimicry plays in the disturbance of immune tolerance and the induction of autoimmunity to the TSHR.
CONTEXT: In addition to genetic susceptibility, Yersinia enterocolitica (YE) infection played an important causative role in the pathogenesis of Graves' disease (GD) through molecular mimicry. However, the specific YE proteins and epitopes recognized by anti-TSH receptor (TSHR) autoantibodies (TRAb) have not been fully clarified, resulting in conflicting results from clinical research. OBJECTIVE: Our aim was to explore the roles of YE in the pathogenesis of GD and identify the YE proteins and epitopes that are similar to the TSHR and are recognized by TRAb. DESIGN: Assays of YE antibodies, TRAb, thyroglobulin antibodies, and thyroid microsomal antibodies as well as cross-absorption and two-way immunodiffusion were performed in patients with GD. Using mass spectrometry and the bioinformatics tools of protein structure modeling and epitope prediction, we identified the YE protein and its epitope, which was recognized by TRAb and was similar to TSHR. RESULTS: Our study demonstrated for the first time that the YE protein outer membrane porin F protein (ompF) shared cross-immunogenicity with a leucine-rich domain of TSHR. The epitope recognized by antihuman TSHR antibody is located within the ompF region of amino acids 190-197, and the polyantibody against ompF protein showed TSAb activity. CONCLUSIONS: Our results suggest that YE ompF is involved in the production of TRAb and the pathogenesis of GD through molecular mimicry. These findings are potentially important for understanding the role molecular mimicry plays in the disturbance of immune tolerance and the induction of autoimmunity to the TSHR.