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 (HT) 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: aa 52-71, 140-176, 240-270, 340-380 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.