Kosin Med J.  2014 Dec;29(2):93-98. 10.7180/kmj.2014.29.2.93.

An overview of the pathogenic mechanisms of autoimmune thyroid disorders

• Park KY

• KMID: 2308493
• DOI: http://doi.org/10.7180/kmj.2014.29.2.93

Abstract

Objectives
, recent epidemiologic studies in humans suggest an increased prevalence of thyroiditis associated with the excessive administration of iodine. More than three times of recommended daily intake of iodine was observed among people in North America. These people generally presented higher level of anti-thyroglobulin antibody, anti-thyroperoxidase antibody, serum thyroid-stimulating hormone and exacerbation of lymphocytic infiltration in thyroid, which indicated the overconsumption of iodine could induce hypothyroidism and enhance the autoimmune response. However, the precise mechanism of excessive iodine intake induced autoimmune thyroid disease remains largely unknown. Over half a century has elapsed since the 1956 identification of thyroglobulin antibodies and the devising of the first experimental model of autoimmune thyroiditis. Since then an incredible amount of experimental work has led to an ever deeper understanding of the nature of thyroid auto-antigens, the main immune mechanisms responsible for Hashimoto's thyroiditis and graves' disease, their genetics, and therir environmental risk factor. Yet, in the majority of genetically predisposed people the individual trigger of thyroid autoimmunity remains obscure. Similarly, effective prevention strategies still remain to be established and, hopefully, will be the target of future studies.

Keyword

Autoimmune; Pathogenic mechanism; Thyroid disorders

MeSH Terms

Antibodies
Autoimmunity
Genetics
Graves Disease
Humans
Hypothyroidism
Iodine
Models, Theoretical
North America
Prevalence
Recommended Dietary Allowances
Risk Factors
Thyroglobulin
Thyroid Diseases
Thyroid Gland*
Thyroiditis
Thyroiditis, Autoimmune
Thyrotropin
Antibodies
Iodine
Thyroglobulin
Thyrotropin

Reference

1.Giulia Cogni., vato Luca Chio. An overview of the pathogenesis of thyroid autoimmunity. Hormones. 2013. 1:19–29.

2.Jenkius RC., weetman AP. Disease association with autoimmune thyroid disease. Thyroid. 2002. 2:977–88.

3.Rosalind S., Brown . Autoimmune Thyroiditis in childhood. Jclin Res Pediatr Endocrinol. 2013. 5:45–9.

4.Rose NR., Bona C. Defining criteria for autoimmune disease. Immunol Today. 1993. 14:426–30.

5.Yoshidab A., Hisa tome I., Taniguchs ., Shirayoshi Y., Yamamoto Y., Miake J, et al. Pendrin is a novel autoantigen recognized by patients with autoimmune thyroid diseases. Jclin Endocrinol Metab. 2009. 94:441–8.

6.Psegnas ., Pirozzi G., Poccoli M., Fratir ., Santoni A., Palmieri G. p38MADK activation controls are the TLR3-mediated up-regulation of cytotoxicity and cytokine production in human NK cells. Blood. 2004. 104:4157–64.

7.Sivori S., Falco M., DellaChiesa M., Carlomagno S., Vitale M., Moretta L, et al. CpG and double-stranded RNA trigger human NK cells by Toll-like receptors: induction of cytokine release and cytotoxicity against tumors and dendritic cells. Proc Natl Acad Sci USA. 2004. 101:10116–21.

8.Foley TP Jr., Abbassi V., Copeland KC., Draznin MB. Brief report; hypothyroidism caused by chronic autoimmune thyroiditis in very young infants. N Engi J Med. 1994. 330:466–8.

9.Gessl A., Wifing A., Agis H., Steiner G., Czernin S., Boltz-Nitulescu G, et al. Activated Naive CD4+ peripheral blood T cells in autoimmune thyroid disease. Thyroid. 1995. 5:117–25.

10.Wang SH., Baker JR. The role of apoptosis in thyroid autoimmunity. Tyhroid. 2007. 17:975–9.

11.Bottazzo GF., Pujol-Borrell R., Hanafusa T., Feldmann M. Role of aberrant HLA-DR expression and antigen presentation in induction of endocrine autoimmunuity. Lancet. 1983. 2:1115–9.

12.Weetman AP. Cellular immune responses in autoimmune thyroid disease. Clin Endocrinol (Oxf). 2004. 61:405–13.

13.Ajjan Ram Kemp EH., Waterman EA., Watson PF., Endo T., Onaya T., Weetman AP. Detection of binding and blocking autoantibodies to the human sodium-iodide symporter in patients with autoimmune thyroid disease, J Clin Endocrinol Metab 2. 0000. 85:2020–7.

14.Yoshida A., Hisatome I., Taniguchi S., Shirayoshi Y., Yamamoto Y., Miake J, et al. Pendrin is a novel autoantigen recongnized by patients with autoimmune thyroid diseases. J Clin Endocrino Metab. 2009. 94:442–8. Epub 2008 Dec 2.

15.Feingold SB., Smith J., Houtz J., Popov sky E., Brown RS. Prevalance and functional significance of thyrotropin receptor blocking antibodies in children and adolescents with chronic lymphocytic thyroiditis. J Clin Endocrinol Metab. 2009. 94:4742. Epub 2009 Oct. 2223.

16.Menconi F., Monti MC., Greenberg DA., Oashi T., Osman R., Davies TF, et al. Molecular amino acid signatures in the MHC class II peptide binding pocket predispose to autoimmune thyroiditis in humans and in mice. Proc Natl Acad Sci USA. 2008. 105:14034–9.

17.Yoshida A., Hisatome I., Taniguchi S., Shirayoshi Y., Yamamoto Y., Miake J, et al. Pendrin is a novel autoantigen recognized by patients with autoimmune thyroid disease. J Clin Endocrinol Metab. 2009. 94:442–8.

18.Vasu C., Dogan RN., Holterman MJ., Prabhakar BS. Selective induction of dendritic cells using granulocyte macrophagecolony stimulating factor, but not fmslike tyrosine kinase receptor 3-ligand, activates thyroglobulin-specific CD4+/CD25+ T cells and suppresses experimental autoimmune thyroiditis. J immunol. 2003. 170:5511–22.

19.Kroemer G., Hirsch F., Conzalez-Garcia A., Martinez C. Differential involvement of Thl and, Th2 cytokines in autoimmune diseases. Autoimmunity. 1996. 24:25–33.

20.Langrish CL., Chen Y., Blumenschein WM., Mattson J., Basham B., Sedgwick JD, et al. IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. J Exp Med. 2005. 201:233–40.

21.Yoshimoto T., Takeda K., Tanaka T., Ohkusu K., Kashiwamura S., Okamura H, et al. IL-12 up-regulates IL-18 receptor expression on T cell, Thl cells, and B cells: synergism with IL-18 for IFN-gamma production. J Immunol. 1998. 161:3400–7.

22.Kong YC., Morris GP., Brown NK., Yan Y., Flynn JC., David CS. Autoimmune thyroiditis: a model uniquely suited to probe regulatory T cell fuction. J Autoimmun. 2009. 33:239–46.

23.Gangi E., Vasu C., Cheatem D., Pravhakar BS. IL-10-producing CD4+CD25+ regulatory T cell play a critical role in granulocyte macrophage colony-stimulating factor-induced suppression of experimental autoimmune thyroiditis. J Immunol. 2005. 174:7006–13.

24.Quaratino S., Badami E., Pang YY., Bartok I., Dyson J., Kioussis D, et al. Degenerate self-reactive human T cell receptor causes spontaneous autoimmune disease in mice. Nat Med. 2004. 10:920–6.

25.Ehlers M., Thiel A., Bernecker C., Porwol D., Papewalis C., Willenberg HS, et al. Evidence of a combined cytotoxic thyroglobulin and thyroperoxidase epitope-specific cellular immunity in Hashimoto's thyroiditis. J Clin Endocrinol Metab. 2012. 97:1347–54.

26.Rotondi M., Chiovato L., Tomagnani S., Serio M., Romagnani P. Role of chemokines in endocrine autoimmune diseases. Endocr Rev. 2007. 28:492–520.

27.Ban Y., Greenberg DA., Concepcion E., Skrabanek ., Villanueva R., Tomer Y. Amino acid substitution in the thyroglobulin gene are associated with susceptibility to human and murine autoimmune thyroid disease. Proc Natl Acad Sci USA. 2003. 100:15119–24.

28.Rose NR., Bonita R., Burek CL. Iodine: an environmental trigger of thyroiditis. Autoimmun Rev. 2002. 1:97–103.

29.Brent GA. Environmental exposures and autoimmune thyroid disease. Thyroid. 2010. 20:755–61.

30.Tomer Y. Genetic susceptibility to autoimmune thyroid disease; past, present, and future. Thyroid. 2010. 20:715–25.

31.Hasham A., Tomer Y. Genetic and epigenetic mechanisms in thyroid autoimmunity. Immunol Res. 2012. 54:204–13.

32.Jacobson EM., Huber AK., Akeno N., Sivak M., Li CW., Concepcion E, et al. A CD40 Kozak sequence polymorphism and susceptibility to antibody-mediated autoimmune conditions: the role of CD40 tissue-specific expression. Genes Immun. 2007. 8:205–14.

33.Burek CL., Talor MV. Environmental triggers of autoimmune thyroiditis. J Autoimmun. 2009. 33:183–9.

34.Duntas LH. Environmental factors and autoimmune thyroiditis. Nat Clin Pract Endocrinol Metab. 2008. 4:454–60.