Amino acid substitutions in the thyroglobulin gene are associated with susceptibility to human and murine autoimmune thyroid disease

The post-translational processing of the TSH receptor (TSHR) includes intra-molecular cleavage with the loss of a 50 amino acid ectodomain region and the formation of two subunits (α and β), followed by likely α subunit shedding. TSHR antibodies (TSHR-Abs), which are directed at the ectodomain, may influence thyroid function by stimulating or inhibiting TSHR signaling or may bind without any such influence (the neutral group of antibodies). When we examined the characteristics of a series of monoclonal TSHR-Abs, we found that many were able to inhibit receptor cleavage and enhance TSHR expression. This was especially apparent with the neutral type of TSHR-Abs directed to the cleaved region of the ectodomain (aa 316–366). Indeed, such inhibition appeared to be epitope dependent with TSHR-Abs directed to regions after residues 335–354 showing no such activity. We propose that this aberrant process, whereby TSHR-Abs influence antigen processing, is a novel mechanism for the maintenance and exacerbation of autoimmune thyroid disease.

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The thyroglobulin gene: the third locus for autoimmune thyroid disease or a false dawn?

Trends in Molecular Medicine ◽

10.1016/j.molmed.2004.05.001 ◽

2004 ◽

Vol 10 (7) ◽

pp. 302-305 ◽

Cited By ~ 7

Author(s):

Stephen Gough

Keyword(s):

Thyroid Disease ◽

Autoimmune Thyroid Disease ◽

Autoimmune Thyroid ◽

The Third ◽

Thyroglobulin Gene

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P232 Polymorphic amino acid variations in the peptide binding pockets of HLA-DQB1* alleles with autoimmune thyroid disease from south India

Human Immunology ◽

10.1016/j.humimm.2017.06.292 ◽

2017 ◽

Vol 78 ◽

pp. 225

Author(s):

Ramgopal Sivanadham ◽

Rathika Chinniah ◽

Padma Malini Ravi ◽

Murali Vijayan ◽

Balakrishnan Karuppiah

Keyword(s):

Amino Acid ◽

Thyroid Disease ◽

Autoimmune Thyroid Disease ◽

South India ◽

Peptide Binding ◽

Autoimmune Thyroid ◽

Binding Pockets

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SEQUENCE SIMILARITY BETWEEN THYROID SELF-PROTEIN AND HEPATITIS C VIRUS POLYPROTEIN: possible triggering mechanism of autoimmune thyroiditis

Arquivos de Gastroenterologia ◽

10.1590/s0004-28032016000300012 ◽

2016 ◽

Vol 53 (3) ◽

pp. 185-191 ◽

Cited By ~ 4

Author(s):

Maristella de Araújo Carvalho SOUSA ◽

Raymundo PARANÁ ◽

Luís Jesuíno de Oliveira ANDRADE

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Amino Acid ◽

Amino Acid Sequence ◽

Thyroid Disease ◽

Autoimmune Thyroid Disease ◽

Molecular Mimicry ◽

Sequence Similarity ◽

Autoimmune Thyroid ◽

Virus Polyprotein

ABSTRACT Background - Exposure to viral antigens that share amino acid sequence similar with self- antigens might trigger autoimmune diseases in genetically predisposed individuals, and the molecular mimicry theory suggests that epitope mimicry between the virus and human proteins can activate autoimmune disease. Objective - The purpose of this study is to explore the possible sequence similarity between the amino acid sequences of thyroid self-protein and hepatitis C virus proteins, using databanks of proteins and immunogenic peptides, to explain autoimmune thyroid disease. Methods - Were performed the comparisons between the amino acid sequence of the hepatitis C virus polyprotein and thyroid self-protein human, available in the database of National Center for Biotechnology Information on Basic Local Alignment Search Tool. Results - The sequence similarity was related each hepatitis C virus genotype to each thyroid antigen. The similarities between the thyroid and the viral peptides ranged from 21.0 % (31 identical residues out of 147 amino acid in the sequence) to 71.0% (5 identical residues out of 7 amino acid in the sequence). Conclusion - Bioinformatics data, suggest a possible pathogenic link between hepatitis C virus and autoimmune thyroid disease. Through of molecular mimicry is observed that sequences similarities between viral polyproteins and self-proteins thyroid could be a mechanism of induction of crossover immune response to self-antigens, with a breakdown of self-tolerance, resulting in autoimmune thyroid disease.

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