Molecular mimicry and autoimmune thyroid disease

Abstract

Hypothesized 40 years ago, molecular mimicry has been thereafter demonstrated as an extremely common mechanism by which microbes elude immune response and modulate biosynthetic/metabolic pathways of the host. In genetically predisposed persons and under particular conditions, molecular mimicry between microbial and human antigens can turn a defensive immune response into autoimmunity. Such triggering role and its pathogenetic importance have been investigated and demonstrated for many autoimmune diseases. However, this is not the case for autoimmune thyroid disease, which appears relatively neglected by this field of research. Here we review the available literature on the possible role of molecular mimicry as a trigger of autoimmune thyroid disease. Additionally, we present the results of in silico search for amino acid sequence homologies between some microbial proteins and thyroid autoantigens, and the potential pathogenetic relevance of such homologies. Relevance stems from the overlap with known autoepitopes and the occurrence of specific HLA-DR binding motifs. Bioinformatics data published by our group support and explain the triggering role of Borrelia, Yersinia, Clostridium botulinum, Rickettsia prowazekii and Helicobacter pylori. Our new data suggest the potential pathogenic importance of Toxoplasma gondii, some Bifidobacteria and Lactobacilli, Candida albicans, Treponema pallidum and hepatitis C virus in autoimmune thyroid disease, indicating specific molecular targets for future research. Additionally, the consistency between in silico prediction of cross-reactivity and experimental results shows the reliability and usefulness of bioinformatics tools to precisely identify candidate molecules for in vitro and/or in vivo experiments, or at least narrow down their number.

Cardiac Autoimmunity: Myocarditis

“…Mimicry implies molecular similarity between non-self (microbial or alloepitopes) and self-epitopes, and the consequent cross-reactivity with T cell clones and/or antibodies (BCR are antibody-like surface receptors) [80, 81]. A paradigmatic example is the association of infections of Campylobacter jejuni with the development of Guillain-Barré syndrome [82].…”

Thyroid Autoimmunity and Antiphospholipid Syndrome: Not Such a Trivial Association

“…In addition, Hofbauer et al (16) hypothesized a molecular mimicry between the epitopes of TSH receptors and β2 glycoprotein 1 as a possible pathogenic mechanism. Benvenga and Guarneri (24) explored this hypothesis through an in silico study and found homologies between various microorganisms and thyroid antigens. Dagenais et al (25) conducted an elegant immunogenetic study on family members with autoimmune diseases highlighting that HLA DR4 and DR7 antigens could predispose patients with GD and high titers of ACL antibodies to develop the full clinical spectrum of APS.…”

A journey from brain to muscle across the thyroid continent

“…[2] before I realized that the abstract had already been published in PubMed! I have received further requests for the same article as well as for other articles [3][4][5] that appear in the present special issue while I had been attending the 86th Annual Meeting of the American Thyroid Association (ATA) in Denver, Colorado, this September. Two of these papers were even mentioned at the discussion of some posters between authors and attendees, and I was invited to provide some further information.…”

“…One might ask why this guest issue contains a number of articles that I myself have coauthored [3][4][5][6][7][8]. Here are the answers.…”

“…Benvenga and Guarneri [4] start showing the relatively scanty literature on molecular mimicry and endocrinology compared to molecular mimicry and other areas; within endocrinology, the thyroid has been quite neglected. In ad hoc tables, they review and summarize the available literature on the possible role of molecular mimicry as a trigger of autoimmune thyroid disease.…”