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Autoimmunity can target protective immunity, leading to infections. Autoantibodies against neutrophils, complement, and cytokines cause various diseases, mimicking genetic immunodeficiencies and explaining unexplained infections.

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Area of Science:

  • Immunology
  • Infectious Diseases
  • Autoimmunity

Background:

  • Human autoimmunity can paradoxically target protective immune mechanisms, a phenomenon termed 'ouroboros'.
  • This autoimmunity involves immune responses against neutrophils, complement, and cytokines, crucial for fighting infections.
  • These autoantibodies can lead to various clinical manifestations, often mimicking primary immunodeficiencies.

Purpose of the Study:

  • To review the concept of autoimmunity against protective immunity ('ouroboros').
  • To analyze the role of autoantibodies against neutrophils, complement, and cytokines in causing infectious diseases.
  • To propose considering this 'ouroboros' phenomenon in patients with unexplained infections.

Main Methods:

  • Literature review of autoimmunity against immune components.
  • Analysis of autoantibodies targeting neutrophils, complement, and specific cytokines (GM-CSF, interferons, IL-6, IL-17A/F).
  • Comparison of disease phenotypes with inborn errors of immunity.

Main Results:

  • Autoantibodies against neutrophils cause neutropenia and mild bacterial infections.
  • Autoantibodies against C3 convertase can enhance complement activity, leading to severe bacterial infections.
  • Autoantibodies neutralizing specific cytokines (GM-CSF, IFN-I, IFN-II, IL-6, IL-17A/F) underlie distinct infectious disease patterns, phenocopying genetic deficiencies.

Conclusions:

  • Autoimmunity against protective immunity ('ouroboros') is a significant factor in recurrent and unexplained infections.
  • Understanding these autoantibodies is crucial for diagnosing and managing patients with idiopathic infectious diseases.
  • This review highlights the need to consider immune dysregulation as a cause of susceptibility to infection.