Advertisement

Reviews in Endocrine and Metabolic Disorders

, Volume 17, Issue 4, pp 485–498 | Cite as

Molecular mimicry and autoimmune thyroid disease

  • Salvatore Benvenga
  • Fabrizio GuarneriEmail author
Article

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.

Keywords

Autoimmune thyroid disease Molecular mimicry Bioinformatics Amino acid sequence homology 

Notes

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Bates HW. Contributions to an insect fauna of the Amazon valley. Lepidoptera: Heliconidae. Trans Linnean Soc. 1862;23:495–566.CrossRefGoogle Scholar
  2. 2.
    Müller F. Ueber die vortheile der mimicry bei schmetterlingen. Zool Anz. 1878;1:54–5.Google Scholar
  3. 3.
    Emsley MG. The mimetic significance of Erythrolamprus aesculapii ocellatus Peters from Tobago. Evolution. 1966;20:663–4.CrossRefGoogle Scholar
  4. 4.
    Wickler W. Mimicry in plants and animals. New York: McGraw-Hill; 1968.Google Scholar
  5. 5.
    Lloyd JE. Aggressive mimicry in photuris: firefly femmes fatales. Science. 1965;149:653–4.CrossRefPubMedGoogle Scholar
  6. 6.
    Guarneri F, Guarneri C. Molecular mimicry in cutaneous autoimmune diseases. World J Dermatol. 2013;2:36–43.CrossRefGoogle Scholar
  7. 7.
    Grossman Z, Paul WE. Autoreactivity, dynamic tuning and selectivity. Curr Opin Immunol. 2001;13:687–98.CrossRefPubMedGoogle Scholar
  8. 8.
    Brower LP, Pough FH, Meck HR. Theoretical investigations of automimicry, I. Single trial learning. Proc Natl Acad Sci U S A. 1970;66:1059–66.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Sturzl M, Hohenadl C, Zietz C, Castanos-Velez E, Wunderlich A, Ascherl G, Biberfeld P, Monini P, Browning PJ, Ensoli B. Expression of K13/v-FLIP gene of human herpesvirus 8 and apoptosis in Kaposi’s sarcoma spindle cells. J Natl Cancer Inst. 1999;91:1725–33.CrossRefPubMedGoogle Scholar
  10. 10.
    Shapiro RF, Wiesner KB, Bryan BL, Utsinger PD, Resnick D, Castles JJ. HLA-B27 and modified bone formation. Lancet. 1976;1:230–1.CrossRefPubMedGoogle Scholar
  11. 11.
    Ebringer A. Ankylosing spondylitis, immune-response-genes and molecular mimicry. Lancet. 1979;1:1186.CrossRefPubMedGoogle Scholar
  12. 12.
    Adams DD. Molecular mimicry and H-Ir genes. Lancet. 1979;2:754.CrossRefPubMedGoogle Scholar
  13. 13.
    Ebringer A. Molecular mimicry and H-Ir genes. Lancet. 1979;2:1143.CrossRefPubMedGoogle Scholar
  14. 14.
    Fujinami RS, Oldstone MB. Molecular mimicry as a mechanism for virus-induced autoimmunity. Immunol Res. 1989;8:3–15.CrossRefPubMedGoogle Scholar
  15. 15.
    Mason D. A very high level of crossreactivity is an essential feature of the T-cell receptor. Immunol Today. 1998;19:395.CrossRefPubMedGoogle Scholar
  16. 16.
    Anderton SM, Wraith DC. Selection and fine-tuning of the autoimmune T-cell repertoire. Nat Rev Immunol. 2002;2:487–98.CrossRefPubMedGoogle Scholar
  17. 17.
    Sospedra M, Martin R. When T cells recognize a pattern, they might cause trouble. Curr Opin Immunol. 2006;18:697–703.CrossRefPubMedGoogle Scholar
  18. 18.
    Ryan KR, Patel SD, Stephens LA, Anderton SM. Death, adaptation and regulation: the three pillars of immune tolerance restrict the risk of autoimmune disease caused by molecular mimicry. J Autoimmun. 2007;29:262–71.CrossRefPubMedGoogle Scholar
  19. 19.
    Anderton SM, Radu CG, Lowrey PA, Ward ES, Wraith DC. Negative selection during the peripheral immune response to antigen. J Exp Med. 2001;193:1–11.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Ohashi PS. T-cell signalling and autoimmunity: molecular mechanisms of disease. Nat Rev Immunol. 2002;2:427–38.PubMedGoogle Scholar
  21. 21.
    Pasare C, Medzhitov R. Toll-like receptors: balancing host resistance with immune tolerance. Curr Opin Immunol. 2003;15:677–82.CrossRefPubMedGoogle Scholar
  22. 22.
    Schwartz RH. T cell anergy. Annu Rev Immunol. 2003;21:305.CrossRefPubMedGoogle Scholar
  23. 23.
    Anderson CC, Chan WF. Mechanisms and models of peripheral CD4 T cell self-tolerance. Front Biosci. 2004;9:2947–63.CrossRefPubMedGoogle Scholar
  24. 24.
    Hildeman DA, Zhu Y, Mitchell TC, Kappler J, Marrack P. Molecular mechanisms of activated T cell death in vivo. Curr Opin Immunol. 2002;14:354–9.CrossRefPubMedGoogle Scholar
  25. 25.
    Guarneri F, Benvenga S. Environmental factors and genetic background that interact to cause autoimmune thyroid disease. Curr Opin Endocrinol Diabetes Obes. 2007;14:398–409.CrossRefPubMedGoogle Scholar
  26. 26.
    Volpé R. A perspective on human autoimmune thyroid disease: is there an abnormality of the target cell which predisposes to the disorder? Autoimmunity. 1992;13:3–9.CrossRefPubMedGoogle Scholar
  27. 27.
    Toivanen P, Toivanen A. Does Yersinia induce autoimmunity? Int Arch Allergy Immunol. 1994;104:107–11.CrossRefPubMedGoogle Scholar
  28. 28.
    Tomer Y, Davies TF. Infections and autoimmune endocrine disease. Bailliere Clin Endocrinol Metab. 1995;9:47–70.CrossRefGoogle Scholar
  29. 29.
    Martin A, Barbesino G, Davies TF. T-cell receptors and autoimmune thyroid disease–signposts for T-cell-antigen driven diseases. Int Rev Immunol. 1999;18:111–40.CrossRefPubMedGoogle Scholar
  30. 30.
    Rao VP, Kajon AE, Spindler KR, Carayanniotis G. Involvement of epitope mimicry in potentiation but not initiation of autoimmune disease. J Immunol. 1999;162:5888–93.PubMedGoogle Scholar
  31. 31.
    Carayanniotis G, Kong YC. Pathogenic thyroglobulin peptides as model antigens: insights on the induction and maintenance of autoimmune thyroiditis. Int Rev Immunol. 2000;19:557–72.CrossRefPubMedGoogle Scholar
  32. 32.
    Chen CR, Tanaka K, Chazenbalk GD, McLachlan SM, Rapoport B. A full biological response to autoantibodies in Graves’ disease requires a disulfide-bonded loop in the thyrotropin receptor N terminus homologous to a laminin epidermal growth factor-like domain. J Biol Chem. 2001;276:14767–72.CrossRefPubMedGoogle Scholar
  33. 33.
    Chen F, Day SL, Metcalfe RA, Sethi G, Kapembwa MS, Brook MG, Churchill D, de Ruiter A, Robinson S, Lacey CJ, Weetman AP. Characteristics of autoimmune thyroid disease occurring as a late complication of immune reconstitution in patients with advanced human immunodeficiency virus (HIV) disease. Medicine (Baltimore). 2005;84:98–106.CrossRefGoogle Scholar
  34. 34.
    Bach JF. Infections and autoimmune diseases. J Autoimmun. 2005;25(Suppl):74–80.CrossRefPubMedGoogle Scholar
  35. 35.
    Vaccaro M, Guarneri F, Borgia F, Cannavò SP, Benvenga S. Association of lichen sclerosus and autoimmune thyroiditis: possible role of Borrelia burgdorferi? Thyroid. 2002;12:1147–8.CrossRefPubMedGoogle Scholar
  36. 36.
    Benvenga S, Guarneri F, Vaccaro M, Santarpia L, Trimarchi F. Homologies between proteins of Borrelia burgdorferi and thyroid autoantigens. Thyroid. 2004;14:964–6.CrossRefPubMedGoogle Scholar
  37. 37.
    Benvenga S, Santarpia L, Trimarchi F, Guarneri F. 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. Thyroid. 2006;16:225–36.CrossRefPubMedGoogle Scholar
  38. 38.
    Guarneri F, Carlotta D, Saraceno G, Trimarchi F, Benvenga S. Bioinformatics support the possible triggering of autoimmune thyroid disease by Yersinia enterocolitica outer membrane proteins homologous to the human thyrotropin receptor. Thyroid. 2011;21:1283–4.CrossRefPubMedGoogle Scholar
  39. 39.
    Gregoric E, Gregoric JA, Guarneri F, Benvenga S. Injections of Clostridium botulinum neurotoxin A may cause thyroid complications in predisposed persons based on molecular mimicry with thyroid autoantigens. Endocrine. 2011;39:41–7.CrossRefPubMedGoogle Scholar
  40. 40.
    Marangou A, Guarneri F, Benvenga S. Graves’ disease precipitated by rickettsial infection. Endocrine. 2015;50:828–9.CrossRefPubMedGoogle Scholar
  41. 41.
    Guarneri F, Guarneri B. Bioinformatic analysis of HLA-linked genetic susceptibility to immunoallergic disease: the MotiFinder software. Ann Ital Dermatol Allergol. 2010;64:69–75.Google Scholar
  42. 42.
    Paparone PW. Hypothyroidism with concurrent Lyme disease. J Am Osteopath Assoc. 1995;95:435–7.PubMedGoogle Scholar
  43. 43.
    Völzke H, Werner A, Guertler L, Robinson D, Wallaschofski H, John U. Putative association between anti-Borrelia IgG and autoimmune thyroid disease? Thyroid. 2005;15:1273–7.CrossRefPubMedGoogle Scholar
  44. 44.
    Bech K, Larsen JH, Hansen JM, Nerup J. Yersinia enterocolitica infection and thyroid disorders. Lancet. 1974;2:951–2.CrossRefPubMedGoogle Scholar
  45. 45.
    Lidman K, Eriksson U, Fagraeus A, Norberg R. Antibodies against thyroid cells in Yersinia enterocolitica infection. Lancet. 1974;2:1449.CrossRefPubMedGoogle Scholar
  46. 46.
    Von Bonsdorff M, Friman C. Yersinia enterocolitica infection and thyroid disorders. Lancet. 1974;2:1565–6.CrossRefGoogle Scholar
  47. 47.
    Arscott P, Rosen ED, Koenig RJ, Kaplan MM, Ellis T, Thompson N, Baker Jr JR. Immunoreactivity to Yersinia enterocolitica antigens in patients with autoimmune thyroid disease. J Clin Endocrinol Metab. 1992;75:295–300.PubMedGoogle Scholar
  48. 48.
    Wenzel BE, Peters A, Zubaschev I. Bacterial virulence antigens and the pathogenesis of autoimmune thyroid disease (AITD). Exp Clin Endocrinol Diabetes. 1996;104(Suppl 4):75–8.CrossRefPubMedGoogle Scholar
  49. 49.
    Chatzipanagiotou S, Legakis JN, Boufidou F, Petroyianni V, Nicolaou C. Prevalence of Yersinia plasmid-encoded outer protein (Yop) class-specific antibodies in patients with Hashimoto’s thyroiditis. Clin Microbiol Infect. 2001;7:138–43.CrossRefPubMedGoogle Scholar
  50. 50.
    Wang Z, Zhang Q, Lu J, Jiang F, Zhang H, Gao L, Zhao J. Identification of outer membrane porin f protein of Yersinia enterocolitica recognized by antithyrotropin receptor antibodies in Graves’ disease and determination of its epitope using mass spectrometry and bioinformatics tools. J Clin Endocrinol Metab. 2010;95:4012–20.CrossRefPubMedGoogle Scholar
  51. 51.
    Hargreaves CE, Grasso M, Hampe CS, Stenkova A, Atkinson S, Joshua GW, Wren BW, Buckle AM, Dunn-Walters D, Banga JP. Yersinia enterocolitica provides the link between thyroid-stimulating antibodies and their germline counterparts in Graves’ disease. J Immunol. 2013;190:5373–81.CrossRefPubMedGoogle Scholar
  52. 52.
    Giménez-Barcons M, Colobran R, Gómez-Pau A, Marín-Sánchez A, Casteràs A, Obiols G, Abella R, Fernández-Doblas J, Tonacchera M, Lucas-Martín A, Pujol-Borrell R. Graves’ disease TSHR-stimulating antibodies (TSAbs) induce the activation of immature thymocytes: a clue to the riddle of TSAbs generation? J Immunol. 2015;194:4199–206.CrossRefPubMedGoogle Scholar
  53. 53.
    Hansen PS, Wenzel BE, Brix TH, Hegedüs L. Yersinia enterocolitica infection does not confer an increased risk of thyroid antibodies: evidence from a Danish twin study. Clin Exp Immunol. 2006;146:32–8.CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Effraimidis G, Tijssen JG, Strieder TG, Wiersinga WM. No causal relationship between Yersinia enterocolitica infection and autoimmune thyroid disease: evidence from a prospective study. Clin Exp Immunol. 2011;165:38–43.CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Vita R, Lapa D, Vita G, Trimarchi F, Benvenga S. A patient with stress-related onset and exacerbations of Graves’ disease. Nat Clin Pract Endocrinol Metab. 2009;5:55–61.CrossRefPubMedGoogle Scholar
  56. 56.
    Vita R, Lapa D, Trimarchi F, Benvenga S. Stress triggers the onset and the recurrences of hyperthyroidism in patients with Graves’ disease. Endocrine. 2015;48:254–63.CrossRefPubMedGoogle Scholar
  57. 57.
    de Luis DA, Varela C, de La Calle H, Cantón R, de Argila CM, San Roman AL, Boixeda D. Helicobacter pylori infection is markedly increased in patients with autoimmune atrophic thyroiditis. J Clin Gastroenterol. 1998;26:259–63.CrossRefPubMedGoogle Scholar
  58. 58.
    Figura N, Di Cairano G, Lorè F, Guarino E, Gragnoli A, Cataldo D, Giannace R, Vaira D, Bianciardi L, Kristodhullu S, Lenzi C, Torricelli V, Orlandini G, Gennari C. The infection by Helicobacter pylori strains expressing CagA is highly prevalent in women with autoimmune thyroid disorders. J Physiol Pharmacol. 1999;50:817–26.PubMedGoogle Scholar
  59. 59.
    Franceschi F, Satta MA, Mentella MC, Penland R, Candelli M, Grillo RL, Leo D, Fini L, Nista EC, Cazzato IA, Lupascu A, Pola P, Pontecorvi A, Gasbarrini G, Genta RM, Gasbarrini A. Helicobacter pylori infection in patients with Hashimoto’s thyroiditis. Helicobacter. 2004;9:369.CrossRefPubMedGoogle Scholar
  60. 60.
    Bertalot G, Montresor G, Tampieri M, Spasiano A, Pedroni M, Milanesi B, Favret M, Manca N, Negrini R. Decrease in thyroid autoantibodies after eradication of Helicobacter pylori infection. Clin Endocrinol. 2004;61:650–2.CrossRefGoogle Scholar
  61. 61.
    Tomasi PA, Dore MP, Fanciulli G, Sanciu F, Realdi G, Delitala G. Is there anything to the reported association between Helicobacter pylori infection and autoimmune thyroiditis? Dig Dis Sci. 2005;50:385–8.CrossRefPubMedGoogle Scholar
  62. 62.
    Sterzl I, Hrda P, Potuznikova B, Matucha P, Hana V, Zamrazil V. Autoimmune thyroiditis and Helicobacter pylori-is there a connection? Neuro Endocrinol Lett. 2006;27(Suppl 1):41–5.PubMedGoogle Scholar
  63. 63.
    Sterzl I, Hrdá P, Matucha P, Cerovská J, Zamrazil V. Anti-Helicobacter pylori, anti-thyroid peroxidase, anti-thyroglobulin and anti-gastric parietal cells antibodies in Czech population. Physiol Res. 2008;57(Suppl 1):S135–41.PubMedGoogle Scholar
  64. 64.
    Bassi V, Santinelli C, Iengo A, Romano C. Identification of a correlation between Helicobacter pylori infection and Graves’ disease. Helicobacter. 2010;15:558–62.CrossRefPubMedGoogle Scholar
  65. 65.
    Bassi V, Marino G, Iengo A, Fattoruso O, Santinelli C. Autoimmune thyroid disease and Helicobacter pylori: the correlation is present only in Graves’ disease. World J Gastroenterol. 2012;18:1093–7.CrossRefPubMedPubMedCentralGoogle Scholar
  66. 66.
    Soveid M, Hosseini Asl K, Omrani GR. Infection by Cag A positive strains of Helicobacter pylori is associated with autoimmune thyroid disease in Iranian patients. Iran J Immunol. 2012;9:48–52.PubMedGoogle Scholar
  67. 67.
    Shi WJ, Liu W, Zhou XY, Ye F, Zhang GX. Associations of Helicobacter pylori infection and cytotoxin-associated gene A status with autoimmune thyroid disease: a meta-analysis. Thyroid. 2013;23:1294–300.CrossRefPubMedGoogle Scholar
  68. 68.
    Aghili R, Jafarzadeh F, Ghorbani R, Khamseh ME, Salami MA, Malek M. The association of Helicobacter pylori infection with Hashimoto’s thyroiditis. Acta Med Iran. 2013;51:293–6.PubMedGoogle Scholar
  69. 69.
    Arslan MS, Ekiz F, Deveci M, Sahin M, Topaloglu O, Karbek B, Tutal E, Ginis Z, Cakal E, Ozbek M, Yuksel O, Delibasi T. The relationship between cytotoxin-associated gene A positive Helicobacter pylori infection and autoimmune thyroid disease. Endocr Res. 2015;40:211–4.CrossRefPubMedGoogle Scholar
  70. 70.
    El-Eshmawy MM, El-Hawary AK, Abdel Gawad SS, El-Baiomy AA. Helicobacter pylori infection might be responsible for the interconnection between type 1 diabetes and autoimmune thyroiditis. Diabetol Metab Syndr. 2011;3:28.CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    Zekry OA, Abd Elwahid HA. The association between Helicobacter pylori infection, type 1 diabetes mellitus, and autoimmune thyroiditis. J Egypt Public Health Assoc. 2013;88:143–7.CrossRefPubMedGoogle Scholar
  72. 72.
    Guarneri F, Alessi A, Trimarchi F, Benvenga S. Helicobacter pylori proteins and thyroid autoantigens share amino acid sequence homology that includes motifs of recognition for HLA molecules and T-cell receptors. 77th Annual meeting of the American Thyroid Association, Phoenix, AZ, USA, October 11–16, 2006. Thyroid. 2006;16:860–1 (Abstract).Google Scholar
  73. 73.
    Larizza D, Calcaterra V, Martinetti M, Negrini R, De Silvestri A, Cisternino M, Iannone AM, Solcia E. Helicobacter pylori infection and autoimmune thyroid disease in young patients: the disadvantage of carrying the human leukocyte antigen-DRB1*0301 allele. J Clin Endocrinol Metab. 2006;91:176–9.CrossRefPubMedGoogle Scholar
  74. 74.
    Tozzoli R, Barzilai O, Ram M, Villalta D, Bizzaro N, Sherer Y, Shoenfeld Y. Infections and autoimmune thyroid diseases: parallel detection of antibodies against pathogens with proteomic technology. Autoimmun Rev. 2008;8:112–5.CrossRefPubMedGoogle Scholar
  75. 75.
    Shapira Y, Agmon-Levin N, Selmi C, Petríková J, Barzilai O, Ram M, Bizzaro N, Valentini G, Matucci-Cerinic M, Anaya JM, Katz BS, Shoenfeld Y. Prevalence of anti-Toxoplasma antibodies in patients with autoimmune diseases. J Autoimmun. 2012;39:112–6.CrossRefPubMedGoogle Scholar
  76. 76.
    Wasserman EE, Nelson K, Rose NR, Rhode C, Pillion JP, Seaberg E, Talor MV, Burek L, Eaton W, Duggan A, Yolken RH. Infection and thyroid autoimmunity: a seroepidemiologic study of TPOaAb. Autoimmunity. 2009;42:439–46.CrossRefPubMedGoogle Scholar
  77. 77.
    Kaňková Š, Procházková L, Flegr J, Calda P, Springer D, Potluková E. Effects of latent toxoplasmosis on autoimmune thyroid diseases in pregnancy. PLoS One. 2014;9:e110878.CrossRefPubMedPubMedCentralGoogle Scholar
  78. 78.
    Kiseleva EP, Mikhailopulo KI, Sviridov OV, Novik GI, Knirel YA, Szwajcer DE. The role of components of Bifidobacterium and Lactobacillus in pathogenesis and serologic diagnosis of autoimmune thyroid disease. Benefic Microbes. 2011;2:139–54.CrossRefGoogle Scholar
  79. 79.
    Felis GE, Dellaglio F, Torriani S. Taxonomy of probiotic microrganisms. In: Charalampopoulos D, Rastall RA, editors. Prebiotics and probiotics science and technology. New York: Springer; 2009. p. 591–637.CrossRefGoogle Scholar
  80. 80.
    Vojdani A, Rahimian P, Kalhor H, Mordechai E. Immunological cross reactivity between Candida albicans and human tissue. J Clin Lab Immunol. 1996;48:1–15.PubMedGoogle Scholar
  81. 81.
    Khoury EL, Pereira L, Greenspan FS. Induction of HLA-DR expression on thyroid follicular cells by cytomegalovirus infection in vitro. Evidence for a dual mechanism of induction. Am J Pathol. 1991;138:1209–23.PubMedPubMedCentralGoogle Scholar
  82. 82.
    Thomas D, Karachaliou F, Kallergi K, Vlachopapadopoulou E, Antonaki G, Chatzimarkou F, Fotinou A, Kaldrymides P, Michalacos S. Herpes virus antibodies seroprevalence in children with autoimmune thyroid disease. Endocrine. 2008;33:171–5.CrossRefPubMedGoogle Scholar
  83. 83.
    Jadali Z, Alavian SM. Autoimmune diseases co-existing with hepatitis C virus infection. Iran J Allergy Asthma Immunol. 2010;9:191–206.PubMedGoogle Scholar
  84. 84.
    Antonelli A, Ferrari SM, Corrado A, Di Domenicantonio A, Fallahi P. Autoimmune thyroid disorders. Autoimmun Rev. 2015;14:174–80.CrossRefPubMedGoogle Scholar
  85. 85.
    Fallahi P, Ferrari SM, Ruffilli I, Elia G, Giuggioli D, Colaci M, Ferri C, Antonelli A. Incidence of thyroid disorders in mixed cryoglobulinemia: results from a longitudinal follow-up. Autoimmun Rev. 2016. doi: 10.1016/j.autrev.2016.03.012.Google Scholar
  86. 86.
    Ferri S, Muratori L, Lenzi M, Granito A, Bianchi FB, Vergani D. HCV and autoimmunity. Curr Pharm Des. 2008;14:1678–85.CrossRefPubMedGoogle Scholar
  87. 87.
    Muratori L, Bogdanos DP, Muratori P, Lenzi M, Granito A, Ma Y, Mieli-Vergani G, Bianchi FB, Vergani D. Susceptibility to thyroid disorders in hepatitis C. Clin Gastroenterol Hepatol. 2005;3:595–603.CrossRefPubMedGoogle Scholar
  88. 88.
    Tomer Y. Hepatitis C and interferon induced thyroiditis. J Autoimmun. 2010;34:J322–6.CrossRefPubMedPubMedCentralGoogle Scholar
  89. 89.
    Menconi F, Hasham A, Tomer Y. Environmental triggers of thyroiditis: hepatitis C and interferon-α. J Endocrinol Investig. 2011;34:78–84.CrossRefGoogle Scholar
  90. 90.
    Martocchia A, Falaschi P. Amino acid sequence homologies between HCV polyprotein and thyroid antigens. Intern Emerg Med. 2007;2:65–7.CrossRefPubMedPubMedCentralGoogle Scholar
  91. 91.
    Akeno N, Blackard JT, Tomer Y. HCV E2 protein binds directly to thyroid cells and induces IL-8 production: a new mechanism for HCV induced thyroid autoimmunity. J Autoimmun. 2008;31:339–44.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.Department of Clinical and Experimental Medicine – EndocrinologyUniversity of MessinaMessinaItaly
  2. 2.Master Program on Childhood, Adolescent and Women’s Endocrine HealthUniversity of MessinaMessinaItaly
  3. 3.Interdepartmental Program on Molecular & Clinical Endocrinology and Women’s Endocrine HealthUniversity Hospital, Policlinico G. MartinoMessinaItaly
  4. 4.Department of Clinical and Experimental Medicine – DermatologyUniversity of MessinaMessinaItaly

Personalised recommendations