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Infectious agents breaking the immunological tolerance: The holy grail in rheumatoid arthritis reconsidered

Elisa Gremese1, Barbara Tolusso2, Dario Bruno3

  • 1Division of Clinical Immunology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy; Immunology Reserach Core Facility, Gemelli Science and Technology Park - Fondazione Policlinico Universitario A. Gemelli IRCCS , Rome, Italy; Università Cattolica del Sacro Cuore, Rome, Italy.

Autoimmunity Reviews
|April 22, 2022
PubMed

Insights

Epstein Barr Virus (EBV) and other infections are investigated for their role in autoimmune diseases like Rheumatoid Arthritis (RA). Only Mycobacterium tuberculosis (MTB), Porphyromonas gingivalis (Pg), and Haemophilus-Glaesserella parasuis (Hps) meet criteria as potential causes.

Area of Science:

  • Immunology
  • Infectious Diseases
  • Rheumatology

Background:

  • Multiple Sclerosis (MS) association with Epstein Barr Virus (EBV) suggests infectious origins for autoimmune diseases.
  • Rheumatoid Arthritis (RA) has historically been treated with antimicrobials, hinting at infectious involvement.
  • Numerous infectious agents have been implicated in RA pathogenesis over time.

Purpose of the Study:

  • To review infectious agents investigated for their role in Rheumatoid Arthritis (RA).
  • To identify which infectious agents satisfy Witebsky's criteria for autoimmune disease causation.
  • To discuss mechanisms of immune tolerance breakdown and potential autoantigens in infection-induced arthritis.

Main Methods:

  • Literature review of studies on infectious agents and Rheumatoid Arthritis (RA).
  • Application of Witebsky's criteria to assess the pathogenetic role of infectious agents.
  • Analysis of animal models demonstrating infectious triggers for arthritis.

Main Results:

  • Several infectious agents, including Streptococcus group A, Proteus, Mycobacterium tuberculosis (MTB), Parvovirus B19, EBV, Porphyromonas gingivalis (Pg), and Haemophilus-Glaesserella parasuis (Hps), have been studied in relation to RA.
  • Only MTB, Pg, and Hps meet Witebsky's criteria as potential causative agents for autoimmune disease.
  • Mechanisms of immune tolerance disruption and autoantigen involvement are explored.

Conclusions:

  • Certain infections, specifically MTB, Pg, and Hps, are strong candidates for triggering Rheumatoid Arthritis (RA).
  • Understanding these infectious links is crucial for developing preventive strategies.
  • Preventive measures against these infections could reduce the burden and severity of RA.
Keywords:
Haemophilus-Glaesserella parasuisImmune toleranceMycobacterium tuberculosisPorphyromonas gingivalisRheumatoid arthritis

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