Homologies between proteins of Borrelia burgdorferi and thyroid autoantigens

Subclinical exposure to microbic antigens that share amino acid sequence homology with self antigens might trigger autoimmune diseases in genetically predisposed individuals via molecular mimicry. Genetic predisposition to Graves' disease (GD) or Hashimoto's thyroiditis (FIT) is conferred by HLA loci DR3 or DR5, respectively. Yersinia enterocolitica (YE) outer proteins (YOPs) are candidate triggers based on the high prevalence of serum antibodies (Ab) against YOPs in autoimmune thyroid diseases (AITD) and reactivity of these Ab with hTSH-R, suggesting homology between YOPs and hTSH-R. We have reported previously that the spirochete Borrelia burgdorferi (Bb) could be another trigger. We have explored further the homology of hTSH-R with YE and Bb. Using the Basic Local Alignment Search Tool (BLAST), we found four matches with YE and five matches with Bb. Residues 22-272, 186-330, 319-363 and 684-749 of hTSH-R matched YopM, Ysp, exopolygalacturonase and SpyA of YE (identity 23-31%, similarity 40-48%). Residues 112-205, 127-150, 141-260, 299-383 and 620-697 of hTSH-R matched outer surface protein A, flagellar motor rotation protein A, two hypothetical proteins (BBG02 and BBJ08) and DNA recombinase/ATP dependent helicase of Borrelia (identity 27-50%%, similarity 40-75%). Interestingly, the above hTSH-R regions coincide with (or include) known human T-cell epitopes: as 52-71, similar to140-176, similar to240-270, similar to340-380 and 441-661. Our data strengthen the hypothesis of Bb and YE as environmental triggers of AITD in genetically predisposed persons through molecular mimicry mechanisms.