Potential targets for the hepatitis C virus-mediated autoimmune thyroiditis
DOI:
https://doi.org/10.11606/issn.2176-7262.rmrp.2021.174934Keywords:
Autoimmune thyroiditis, Hepatitis C virus, Signaling pathwayAbstract
Introduction: The mechanisms by which hepatitis C virus (HCV) infection induces autoimmune thyroiditis (AIT) have been studied, and it was suggested that inflammatory cytokines during HCV infection would change the thyroperoxidase (TPO) signaling cascade and thyroglobulin (Tg) determining autoimmune thyroid disease.
Objective: To show the signaling pathway, of TPO and Tg, and their potential targets mediated HCV in individuals with hepatitis C.
Methods: The mapping of the signaling pathway was based on a review study approach and performed using the automatic annotation server of the Kyoto and Genome Encyclopedia (KEGG). PathVisio is free software for analysis and design of open source routes, and was used for the graphic representation of the signaling pathway.
Results: The contigs were extracted from the KEGG database and their mapped transcription represents the signaling pathway of the main biomolecules that triggers the AIT. The action of HCV, or its treatment can trigger AIT that is characterized by the presence of autoantibodies against TPO and Tg. In AIT, autoreactive CD4 + T lymphocytes recruit B cells and CD8 + T cells in the thyroid. The progression of the disease leads to the death of thyroid cells
and hypothyroidism.
Conclusion: HCV or its treatment activates several signaling pathways with thyroid cells damage resulting in AIT and secondary hypothyroidism to cellular apoptosis.
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References
Paek E, Park J, Lee KJ. Multi-layered representation for cell signaling pathways. Mol Cell Proteomics. 2004;3(10):1009-22.
Brent GA. Mechanisms of thyroid hormone action. J Clin Invest. 2012;122(9):3035-43.
Andrade LJ, Atta AM, Atta ML, Mangabeira CN, Paraná R. Thyroid disorders in patients with chronic hepatitis C using interferon-alpha and ribavirin therapy. Braz J Infect Dis. 2011;15(4):377-81.
Andrade LJ, D'Oliveira A Jr, Silva CA, et al. A meta-analysis of patients with chronic hepatitis C treated with interferon-alpha to determine the risk of autoimmune thyroiditis. Acta Gastroenterol Latinoam. 2011;41(2):104-10.
Obołończyk Ł, Siekierska-Hellmann M, Wiśniewski P, et al. Epidemiology, risk factors and prognosis of Interferon alpha induced thyroid disorders. A Prospective Clinical Study. Postepy Hig Med Dosw (Online). 2017;71(0):842-849.
Blackard JT, Kong L, Huber AK, Tomer Y. Hepatitis C virus infection of a thyroid cell line: implications for pathogenesis of hepatitis C virus and thyroiditis. Thyroid. 2013;23(7):863-70.
Ogata H, Goto S, Sato K, Fujibuchi W, Bono H, Kanehisa M. KEGG: Kyoto Encyclopedia of Genes and Genomes. Nucleic Acids Res. 1999;27(1):29-34.
Kutmon M, van Iersel MP, Bohler A, et al. PathVisio 3: an extendable pathway analysis toolbox. PLoS Comput Biol. 2015;11(2):e1004085.
Ferri C, Colaci M, Fallahi P, Ferrari SM, Antonelli A, Giuggioli D. Thyroid Involvement in Hepatitis C Virus-Infected Patients with/without Mixed Cryoglobulinemia. Front Endocrinol (Lausanne). 2017;8:159.
Vasu C, Gorla SR, Prabhakar BS, Holterman MJ. Targeted engagement of CTLA-4 prevents autoimmune thyroiditis. Int Immunol. 2003;15(5):641-54.
Tomoyose T, Komiya I, Takara M, et al. Cytotoxic T-lymphocyte antigen-4 gene polymorphisms and human T-cell lymphotrophic virus-1 infection: their associations with Hashimoto's thyroiditis in Japanese patients. Thyroid. 2002;12(8):673-7.
Many MC, Maniratunga S, Varis I, Dardenne M, Drexhage HA, Denef JF. Two-step development of Hashimoto-like thyroiditis in genetically autoimmune prone non-obese diabetic mice: effects of iodine-induced cell necrosis. J Endocrinol. 1995;147(2):311-20.
Patsoukis N, Weaver JD, Strauss L, Herbel C, Seth P, Boussiotis VA. Immunometabolic Regulations Mediated by Coinhibitory Receptors and Their Impact on T Cell Immune Responses. Front Immunol. 2017;8:330.
Marguerie C, Lunardi C, So A. PCR-based analysis of the TCR repertoire in human autoimmune diseases. Immunol Today. 1992;13(9):336-8.
Salomon B, Bluestone JA. Complexities of CD28/B7: CTLA-4 costimulatory pathways in autoimmunity and transplantation. Annu Rev Immunol. 2001;19:225-52.
Weetman AP. An update on the pathogenesis of Hashimoto's thyroiditis. J Endocrinol Invest. 2020 Dec 17.
Pyzik A, Grywalska E, Matyjaszek-Matuszek B, Roliński J. Immune disorders in Hashimoto's thyroiditis: what do we know so far? J Immunol Res. 2015;2015:979167.
Hammerstad SS, Stefan M, Blackard J, et al. Hepatitis C Virus E2 Protein Induces Upregulation of IL-8 Pathways and Production of Heat Shock Proteins in Human Thyroid Cells. J Clin Endocrinol Metab. 2017;102(2):689-697.
Kaiko GE, Horvat JC, Beagley KW, Hansbro PM. Immunological decision-making: how does the immune system decide to mount a helper T-cell response? Immunology. 2008;123(3):326-38.
Tomer Y. Genetic dissection of familial autoimmune thyroid diseases using whole genome screening. Autoimmun Rev. 2002;1(4):198-204.
Harvey BP, Gee RJ, Haberman AM, Shlomchik MJ, Mamula MJ. Antigen presentation and transfer between B cells and macrophages. Eur J Immunol. 2007;37(7):1739-51.
Armengol MP, Sabater L, Fernández M, et al. Influx of recent thymic emigrants into autoimmune thyroid disease glands in humans. Clin Exp Immunol. 2008;153(3):338-50.
Ferrari SM, Fallahi P, Antonelli A, Benvenga S. Environmental Issues in Thyroid Diseases. Front Endocrinol (Lausanne). 2017;8:50.
Du W, Cao X. Cytotoxic Pathways in Allogeneic Hematopoietic Cell Transplantation. Front Immunol. 2018;9:2979.
Yamada A, Arakaki R, Saito M, Kudo Y, Ishimaru N. Dual Role of Fas/FasL-Mediated Signal in Peripheral Immune Tolerance. Front Immunol. 2017;8:403.
Hidaka Y, Amino N, Iwatani Y, et al. Increase in peripheral natural killer cell activity in patients with autoimmune thyroid disease. Autoimmunity. 1992;11(4):239-46.
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Copyright (c) 2021 Luis Jesuino Oliveira Andrade, Luisa Correia Matos de Oliveira, Gabriela Correia Matos de Oliveira
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