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Remnant Epitopes Generating Autoimmunity: From Model to Useful Paradigm.

Ghislain Opdenakker1, Ahmed Abu El-Asrar2, Jo Van Damme3

  • 1Laboratory of Immunobiology, Department of Microbiology and Immunology, Rega Institute for Medical Research, KU Leuven, University of Leuven, Leuven, Belgium.

Trends in Immunology
|April 18, 2020
PubMed
Summary

The remnant epitopes generate autoimmunity (REGA) model explains how autoimmune diseases develop. This refined model shows remnant epitopes are key to autoimmunity, influenced by genetics and epigenetics, with therapeutic potential.

Keywords:
AutoimmunityChemokinesCitrullinationCytokinesGlycationPost-translational modificationProteases

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Area of Science:

  • Immunology
  • Autoimmunity
  • Molecular Biology

Background:

  • Autoimmune diseases involve adaptive immunity, characterized by autoantibodies or autoreactive T cells.
  • Autoreactivity is a normal immune process, posing challenges in understanding disease mechanisms.
  • The 'remnant epitopes generate autoimmunity' (REGA) model was previously proposed.

Purpose of the Study:

  • To refine the REGA model for understanding autoimmune disease pathogenesis.
  • To explore the role of remnant epitopes in generating, maintaining, and regulating autoimmunity.
  • To investigate the influence of genetic and epigenetic factors on autoantigen production.

Main Methods:

  • The refined REGA model was tested across various autoimmune conditions.
  • Analysis of autoantigen generation by extracellular proteases from innate immune cells.
  • Evaluation of disease phase-specific autoantigen production.

Main Results:

  • The refined REGA model provides a paradigm for autoimmunity.
  • Remnant epitopes are central to the generation, maintenance, and regulation of autoimmune responses.
  • Autoantigen production is influenced by genetic and epigenetic factors and varies with disease stage.

Conclusions:

  • The REGA model offers a comprehensive framework for autoimmune disease development.
  • Targeting remnant epitopes presents potential therapeutic strategies for autoimmune diseases.
  • Understanding the dynamics of autoantigen production is crucial for managing autoimmunity.