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The Intricate Dance of Infections and Autoimmunity: An Interesting Paradox

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Indian Journal of Pediatrics Aims and scope Submit manuscript

Abstract

Besides genetic susceptibility, infections due to viruses, bacteria and protozoa have been implicated in the development of autoimmune diseases (AD). AD can be triggered in a genetically susceptible individual by infections that disrupt immunological tolerance towards self-antigens. Pathogens can initiate autoimmunity by way of molecular mimicry, bystander activation, epitope spreading or persistent infection with polyclonal activation. This review covers two main topics: (i) the mechanisms by which an infectious agent can trigger or worsen autoimmunity; and (ii) the correlation between specific infectious agents and AD in humans with special emphasis on multisystem inflammatory syndrome in children (MIS-C).

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References

  1. Tangye SG, Al-Herz W, Bousfiha A, et al. Human inborn errors of immunity: 2022 update on the classification from the International Union of Immunological Societies Expert Committee. J Clin Immunol. 2022;42:1473–507.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Schoenfeld Y, Isenberg D. The mosaic of autoimmunity. Immunol Today. 1989;10:123–6.

    Article  Google Scholar 

  3. Floreani A, Leung PS, Gershwin ME. Environmental basis of autoimmunity. Clin Rev Allergy Immunol. 2016;50:287–300.

    Article  PubMed  CAS  Google Scholar 

  4. Delogu LG, Deidda S, Delitala G, Manetti R. Infectious diseases and autoimmunity. J Infect Dev Ctries. 2011;5:679–87.

    Article  PubMed  Google Scholar 

  5. Kivity S, Agmon-Levin N, Blank M, Shoenfeld Y. Infections and autoimmunity - friends or foes? Trends Immunol. 2009;30:409–14.

    Article  PubMed  CAS  Google Scholar 

  6. Kudat H, Telci G, Sozen AB, et al. The role of HLA molecules in susceptibility to chronic rheumatic heart disease. Int J Immunogenet. 2006;33:41–4.

    Article  PubMed  CAS  Google Scholar 

  7. Wanstrat A, Wakeland E. The genetics of complex autoimmune diseases: Non-MHC susceptibility genes. Nat Immunol. 2001;2:802–9.

    Article  Google Scholar 

  8. Galli L, Chiappini E, de Martino M. Infections and autoimmunity. Pediatr Infect Dis J. 2012;31:1295–7.

    Article  PubMed  Google Scholar 

  9. Anaya J-M, Shoenfeld Y, Rojas-Villarraga A, Levy RA, Cervera R. Autoimmunity: From Bench to Bedside [Internet]. Bogota (Colombia): El Rosario University Press; 2013 Jul 18. PMID: 29087650.

    Google Scholar 

  10. Arbuckle MR, McClain MT, Rubertone MV, et al. Development of autoantibodies before the clinical onset of systemic lupus erythematosus. New Engl J Med. 2003;349:1526–33.

    Article  PubMed  CAS  Google Scholar 

  11. Riphagen S, Gomez X, Gonzalez-Martinez C, Wilkinson N, Theocharis P. Hyperinflammatory shock in children during COVID-19 pandemic. Lancet. 2020;395:1607–8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  12. Verdoni L, Mazza A, Gervasoni A, et al. An outbreak of severe Kawasaki-like disease at the Italian epicentre of the SARS-CoV-2 epidemic: An observational cohort study. Lancet. 2020;395:1771–8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. McMurray JC, May JW, Cunningham MW, Jones OY. Multisystem inflammatory syndrome in children (MIS-C), a post-viral myocarditis and systemic vasculitis—a critical review of its pathogenesis and treatment. Front Pediatr. 2020;8:626182.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Bartsch YC, Wang C, Zohar T, et al. Humoral signatures of protective and pathological SARS-CoV-2 infection in children. Nat Med. 2021;27:454–62.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  15. Carter MJ, Fish M, Jennings A, et al. Peripheral immunophenotypes in children with multisystem inflammatory syndrome associated with SARS-CoV-2 infection. Nat Med. 2020;26:1701–7.

    Article  PubMed  CAS  Google Scholar 

  16. Lee PY, Day-Lewis M, Henderson LA, et al. Distinct clinical and immunological features of SARS-CoV-2-induced multisystem inflammatory syndrome in children. J Clin Invest. 2020;130:5942–50.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  17. Shulman ST. Pediatric coronavirus disease-2019–associated multisystem inflammatory syndrome. J Pediatric Infect Dis Soc. 2020;9:285–6.

    Article  PubMed  CAS  Google Scholar 

  18. Sharma C, Ganigara M, Galeotti C, et al. Multisystem inflammatory syndrome in children and Kawasaki disease: A critical comparison. Nat Rev Rheumatol. 2021;17:731–48.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  19. Diorio C, McNerney KO, Lambert M, et al. Evidence of thrombotic microangiopathy in children with SARS-CoV-2 across the spectrum of clinical presentations. Blood Adv. 2020;4:6051–63.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. Kaushik S, Aydin SI, Derespina KR, et al. Multisystem inflammatory syndrome in children associated with severe acute respiratory syndrome coronavirus 2 infection (MIS-C): A multi-institutional study from New York City. J Pediatr. 2020;224:24–9.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  21. Ouldali N, Toubiana J, Antona D, et al; French Covid-19 Paediatric Inflammation Consortium. Association of intravenous immunoglobulins plus methylprednisolone vs immunoglobulins alone with course of fever in multisystem inflammatory syndrome in children. JAMA. 2021;325:855–64.

    Article  PubMed  CAS  Google Scholar 

  22. Nakra NA, Blumberg DA, Herrera-Guerra A, Lakshminrusimha S. Multi-system inflammatory syndrome in children (MIS-C) following SARS-CoV-2 infection: Review of clinical presentation, hypothetical pathogenesis, and proposed management. Children (Basel). 2020;7:69.

    PubMed  Google Scholar 

  23. Martínez-García JJ, López-Acosta JR, Arce-Cabrera D, et al. Case report: Multisystem inflammatory syndrome in children associated with COVID-19, macrophage activation syndrome, and incomplete Kawasaki disease. Front Pediatr. 2023;11:1167828.

    Article  PubMed  PubMed Central  Google Scholar 

  24. James JA, Neas BR, Moser KL, et al. Systemic lupus erythematosus in adults is associated with previous Epstein-Barr virus exposure. Arthritis Rheum. 2001;44:1122–6.

    Article  PubMed  CAS  Google Scholar 

  25. Toussirot É, Roudier J. Epstein-Barr virus in autoimmune diseases. Best Pract Res Clin Rheumatol. 2008;22:883–96.

    Article  PubMed  CAS  Google Scholar 

  26. Kang I, Quan T, Nolasco H, et al. Defective control of latent Epstein-Barr virus infection in systemic lupus erythematosus. J Immunol. 2004;172:1287–94.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Pediatric Rheumatology, Manipal Hospital, HAL Airport Road, Bengaluru, Karnataka, India

    Anand Prahalad Rao & Debasis Patro

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  1. Anand Prahalad Rao
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  2. Debasis Patro
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Both the authors have contributed equally to the drafting of the article and final edits were done by APR. APR will act as guarantor for this manuscript.

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Correspondence to Anand Prahalad Rao.

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Rao, A.P., Patro, D. The Intricate Dance of Infections and Autoimmunity: An Interesting Paradox. Indian J Pediatr (2023). https://doi.org/10.1007/s12098-023-04928-8

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