Role of infections in autoimmune disease development

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Abstract

Since the discovery of immunologic tolerance phenomenon, active discussion of the role of genetic and environmental factors in autoimmune disease development has persisted. One of such factors is infections. Microorganisms are considered to be triggers of autoimmune diseases but their role is still not completely understood. Animal experiments conclusively demonstrate how the certain microorganism or its antigen can cause autoimmune pathology. At the same time the results of clinical studies performed on patients with different autoimmune pathologies are hardly decisive and often are contradictory. It should be taken into account that patients with already existing disease were studied in most cases, so interpretation of the data on the association of certain causative pathogens with certain autoimmune pathology should be performed cautiously. The review contains key hypotheses about possible mechanisms of autoimmune reaction development in infections: hypotheses about latent antegens/cryptoantigens, antigen modification, superantigen presence, epitope spectrum extension, molecular mimicry, adjuvant and non-specific effect, antigen complementarity, and idiotypic-antiidiotypic interactions. Their advantages and disadvantages are presented, their comparison is performed. In most cases facts proving one of the hypotheses can be reconsidered in favor of another one. A number of early hypotheses need to be reviewed taking into account modern understanding of innate and adaptive immunity. As more data about relation between infection and autoimmunity is collected, new hypotheses can be developed integrating main claims of previous hypotheses and adding the new ones.

About the authors

O V Moskalets

Moscow Regional Scientific Research and Clinical Institute

Email: 6816000@mail.ru
Moscow, Russia

References

  1. Walker L.S., Abbas A.K. The enemy within: keeping self-reactive T-cells at bay in the periphery. Nat. Rev. Immunol. 2002; 2 (1): 11-19. doi: 10.1038/nri701.
  2. Ярилин А.А. Основы иммунологии. Учебник. М.: Медицина. 1999; 608 с.
  3. Полетаев А.Б. Иммунофизиология и иммунопатология. М: МИА. 2008; 208 с.
  4. Shoenfield Y., Blank M., Abu-Shskra M. et al. The mosaic of autoimmunity: prediction, autoantibodies and therapy in autoimmune diseases - 2008. IMAJ. 2008; 10: 13-19.
  5. Selgrade M.K., Cooper G.S., Germolec D.R., Heindel J.J. Linking environmental agents and autoimmune disease: an agenda for future research. Environ. Health Perspect. 1999; 107 (Suppl. 5): 811-813. doi: 10.1289/ehp.99107s5811.
  6. Samarkos M., Vaiopoulos G. The role of infections in the pathogenesis of autoimmune disease. Curr. Drug. Targets Inflamm. Allergy. 2005; 4 (1): 99-103. doi: 10.2174/1568010053622821.
  7. Ercolini A.M., Miller S.D. The role of infection in autoimmune disease. Clin. Exp. Immunol. 2009; 155 (1): 1-15. doi: 10.1111/j.1365-2249.2008.03834.x.
  8. Delogou L.G., Deidda S., Delitala G., Manetti R. Infectious diseases and autoimmunity. J. Infect. Dev. Ctries. 2011; 5 (10): 679-687. doi: 10.3855/jidc.2061.
  9. Sakkas L.I., Bogdanos D.P. Infections as a cause of autoimmune rheumatic diseases. Auto. Immune. Highlights. 2016; 7 (1): 13. doi: 10.1007/s13317-016-0086-x.
  10. Vergani D., Mieli-Vergani G. Autoimmune manifestations in viral hepatitis. Semin. Immunopathol. 2013; 35 (1): 73-85. doi: 10.1007/s00281-012-0328-6.
  11. Narciso-Schavion J.L., Schavion L. de L. Autoantibodies in chronic hepatitis C: a clinical perspective. World J. Hepatol. 2015; 7 (8): 1074-1085. doi: 10.4254/wjh.v7.i8.1074.
  12. Postnett D.N. Herpesviruses and autoimmunity. Curr. Opin. Investig. Drugs. 2008; 9 (5): 505-514.
  13. Dittfeld A., Gwizdek K., Michalski M., Wojnicz R. A possible link between the Epstein-Barr infection and autoimmune thyroid disorders. Cent. Eur. Immunol. 2016; 41 (3): 297-301. doi: 10.5114/ceji.2016.63130.
  14. Whitton J.L., Feuer R. Myocarditis, microbes and autoimmunity. Autoimmunity. 2004; 37 (5): 375-386. doi: 10.1080/08916930410001713089.
  15. Pankuweit S., Klingel K. Viral myocarditis: from experimental models to molecular diagnosis in patients. Heart Fail. Rev. 2013; 18 (6): 683-702. DOI: 10.1007/s 1074-012-9357-4.
  16. Massilamany C., Gangaplara A., Reddy J. Intricacies of cardiac damage in Coxsackievirus B3 infection: implications for therapy. Int. J. Cardiol. 2014; 177 (2): 330-339. doi: 10.1016/j.ijcard.2014.09.136.
  17. Cunningham M.W. Streptococcus and rheumatic fever. Curr. Opin. Rheumatol. 2012; 24 (4): 408-416. doi: 10.1097/BOR.0b013e32835461d3.
  18. Chakravarty S.D., Zabriskie J.B., Gibofsky A. Acute rheumatic fever and streptococci: the quintessential pathogenic trigger of autoimmunity. Clin. Rheumatol. 2014; 33 (7): 893-901. DOI: 10.1007/s 10067-014-2698-8.
  19. Roszkiewicz J., Smolewska E. Kaleidoscope of autoimmune diseases in HIV infection. Rheumatol. Int. 2016; 36 (11): 1481-1491. doi: 10.1007/s00296-016-3555-7.
  20. Smyk D.S., Koutsoumpas A.L., Mitilinaiou M.G. et al. Helicobacter pylori and autoimmune disease: cause or bystander. World J. Gastroenterol. 2014; 20 (3): 613-629. doi: 10.3748/wjg.v20.i3.613.
  21. Гульнева М.Ю., Носков С.М., Малафеева Э.В. Оппортунистические микроорганизмы при ревматических заболеваниях. Науч.-практ. pевматол. 2016; 54 (1): 100-104. doi: 10.14412/1995-4484-2016-100-104.
  22. Nielsen P.R., Kragstrup T.W., Deleuran B.W., Benrose M.E. Infections as risk factor for autoimmune disease - A nationalwide studi. J. Autoimmun. 2016; 74: 176-181. doi: 10.1016/j.jaut.2016.05.013.
  23. Root-Bernstein R., Fairweather D. Complexities in the relationship between infection and autoimmunity. Curr. Allergy Asthma Rep. 2014; 14 (1): 407. doi: 10.1007/s11882-013-0407-3.
  24. Vanderlught C.L., Miller S.D. Epitope spreading in immune-mediated diseases:implications for autoimmunity. Natura Rev. Immunol. 2002; 2 (2): 85-95. doi: 10.1038/nri724.
  25. Miller S.D., Katz-Levy Y., Neville K.L., Vanderlught C.L. Virus-induced autoimmunity: epitope spreading to myelin autoepitopes in Theiler’s virus infection of the central nervous system. Adv. Virus Res. 2001; 56: 199-217.
  26. Matsumoto Y., Park I.K., Kohyama K. B-cell epitope spreading is a critical step for the switch from C-protein induced myocarditits to dilated cardiomyopathy. Am. J. Pathol. 2007; 170 (1): 43-51. doi: 10.2353/ajpath.2007.060544.
  27. Opdenakker G., Proost P., Van Damme J. Microbiomic and posttranslational modifications as preludes to autoimmune diseases. Trends Mol. Med. 2016; 22 (9): 746-757. doi: 10.1016/j.molmed.2016.07.002.
  28. Takahashi K. Influence of bacteria on epigenetic gene control. Cell. Mol. Life Sci. 2014; 71 (6): 1045-1054. doi: 10.1007/s00018-013-1487-x.
  29. Costenbader K.H., Gay S., Alarcón-Riquelme M.E. et al. Genes, epigenetic regulation and enviromental factors: which is the most relevant in developing autoimmune diseases? Autoimmun. Rev. 2012; 11 (8): 604-609. doi: 10.1016/j.autrev.2011.10.022.
  30. Somers E.C., Richardson B.C. Environmental exposures, epigenetic changes and the risk of lupus. Lupus. 2014; 23 (6): 568-576. doi: 10.1177/0961203313499419.
  31. Lawson C.M. Evidence for mimicry by viral agents in animal models of autoimmune disease including myocarditis. Cell. Moll. Life Sci. 2000; 57 (4): 552-560. doi: 10.1007/PL00000717.
  32. Wucherphenning K.W. Mechanisms for the induction of autoimmunity by infectious agents. J. Clin. Invest. 2001; 108 (8): 1097-1104. doi: 10.1172/JCI14235.
  33. Cusick M.F., Libbey J.E., Fujinami R.S. Molecular mimicry as a mechanism of autoimmune disease. Clin. Rev. Allerg. Immunol. 2012; 42: 102-111. DOI: 10.1007/s 12016-011-8294-7.
  34. Rose N.R., Mackay I.R. Molecular mimicry: a critical look at exemplary instances in human diseases. Cell. Mol. Life Sci. 2001; 57 (4): 542-551. doi: 10.1007/PL00000716.
  35. Fujinami R.S., von Herrath M.G., Christen U., Whitton J.L. Molecular mimicry, bystander activation, or viral persistence: infections and autoimnune disease. Clin. Microbiol. Rev. 2006; 19 (1): 80-94. doi: 10.1128/CMR.19.1.80-94.2006.
  36. Plotz P.H. Autuantibodies are anti-idiotype antibodies to antiviral antibodies. Lancet. 1983; 322 (8354): 824-826.
  37. Weremeichik H., Moraska A., Herzum M. et al. Naturally occurring anti-idiotypic antibodies - mechanisms for autoimmunity and immunoregulation? Eur. Heart J. 1991; 12 (Suppl. D): 154-157.
  38. Sundberg E.J., Deng L., Mariuzza R.A. TCR recognition of peptide/MHC class II complexes and superantigens. Semin. Immunol. 2007; 19 (4): 262-271. doi: 10.1016/i.s.mim.2007.04.006.
  39. Getts D.R., Chastain E.M., Terry R.L., Miller S.D. Virus infection, antiviral immunity, and autoimmunity. Immunol. Rev. 2013; 255 (1): 197-209. doi: 10.1111/imr.12091.
  40. Dar S.A., Janahi E.M., Haque S. et al. Superantigenes influence in conjunction with cytokine polymorphism potentiates autoimmunity in systemic lupus erythematosus patients. Immunol. Res. 2016; 64 (4): 1001-1012. doi: 10.1007/s12026-015-8768-4.
  41. Dar S.A., Das S., Bhattacharya S.N. et al. Possible role of superantigens in inducing autoimmunity in pemphigus patients. J. Dermatol. 2011; 38 (10): 980-987. doi: 10.1111/j.1346-8138.2011.01253.x.
  42. Mills K.H.G. TLR-dependent T-cell activation in autoimmunity. Nat. Rev. Immunol. 2011; 11 (12): 807-822. doi: 10.1038/nri3095.
  43. Owens G.P., Benett J.L Trigger, pathogen, or bystander: the complex nexus linking Epstain-Barr virus and multiple sclerosis. Multiple Sclerosis J. 2012; 18 (9): 1204-1208. doi: 10.1177/1352458512448109.
  44. Masters S.L. Specific inflammosomes in complex diseases. Clin. Immunol. 2013; 147 (3): 223-228. doi: 10.1016/j.clim.2012.12.006.
  45. Kleinewietfeld M., Hafler D.A. The plasticity of human Treg and Th17 cells and its role in autoimmunity. Semin. Immunol. 2013; 25 (4): 305-312. doi: 10.1016/j.smim.2013.10.009.
  46. Pendegraft W.F., Badhwar A.K., Preston G.A. Autoantigen complementarity and its contributions to hallmarks of autoimmune disease. J. Theor. Biol. 2015; 375: 88-94. doi: 10.1016/j.jtbi.2014.12.006.

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