Borrelia burgdorferi and thyroid autoantigens

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Thyroid. 2004 Nov;14(11):964-6.

Homologies between proteins of Borrelia burgdorferi and thyroid
autoantigens.

Benvenga S, Guarneri F, Vaccaro M, Santarpia L, Trimarchi F.

Sezione di Endocrinologia del Dipartimento Clinico Sperimentale di
Medicina e Farmacologia, Universita di Messina, Messina, Italy.
s.benvenga@xxxxxxxxxxxxx

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.

PMID: 15671776 [PubMed - indexed for MEDLINE]
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Thyroid. 2006 Mar;16(3):225-236.

Human Thyroid Autoantigens and Proteins of Yersinia and Borrelia
Share Amino Acid Sequence Homology That Includes Binding Motifs to
HLA-DR Molecules and T-Cell Receptor.

Benvenga S, Santarpia L, Trimarchi F, Guarneri F.

Sezione di Endocrinologia del Dipartimento Clinico Sperimentale di
Medicina e Farmacologia, Universita di Messina, Messina, Italy.,
Programma Infradipartimentale di Endocrinologia Molecolare Clinica,
Azienda Ospedaliera Universitaria Policlinico Gaetano Martino, Messina,

Italy., Master universitario di II livello Endocrinologia
dell'Infanzia,
dell'Adolescenza e della Donna, Universita di Messina, Messina, Italy.

We previously reported that the spirochete Borrelia burgdorferi
could trigger autoimmune thyroid diseases (AITD). Subsequently, we
showed local amino acid sequence homology between all human thyroid
autoantigens (human thyrotropin receptor [hTSH-R], human thyroglobulin
[hTg], human thyroperoxidase [hTPO], human sodium iodide symporter
[hNIS]) and Borrelia proteins (n = 6606), and between hTSH-R and
Yersinia enterocolitica (n = 1153). We have now updated our search of
homology with Borrelia (n = 11,198 proteins) and extended our search on

Yersinia to the entire species (n = 40,964 proteins). We also searched
the homologous human and microbial sequences for peptide-binding motifs

of HLA-DR molecules, because a number of these class II major
histocompatibility complex (MHC) molecules (DR3, DR4, DR5, DR8, and
DR9)
are associated with AITD. Significant homologies were found for only 16

Borrelia proteins (5 with hTSH-R, 2 with hTg, 3 with hTPO, and 6 with
hNIS) and only 19 Yersinia proteins (4 with hTSH-R, 2 with hTg, 2 with
hTPO, and 11 with hNIS). Noteworthy, segments of thyroid autoantigens
homologous to these microbial proteins are known to be autoantigenic.
Also, the hTSH-R homologus region of one Borrelia protein (OspA)
contains an immunodominant epitope that others have found to be
homologous to hLFA-1. This is of interest, as the hLFA-1/ICAM-1
ligand/receptor pair is aberrantly expressed in the follicular cells of

thyroids affected by Hashimoto's thyroiditis. A computer-assisted
search
detected antigenic peptide binding motifs to the DR molecules
implicated
in AITD. In conclusion, our in silico data do not directly demonstrate
that Borrelia and Yersinia proteins trigger AITD but suggest that a
restricted number of them might have the potential to, at least in
persons with certain HLA-DR alleles.

PMID: 16571084 [PubMed - as supplied by publisher]

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