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Where, How, and When: Positioning Posttranslational Modification Within Type 1 Diabetes Pathogenesis.

Rene J McLaughlin1, Matthew P Spindler1, Menno van Lummel1

  • 1Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, E3-Q, PO Box 9600, 2300 RC, Leiden, The Netherlands.

Current Diabetes Reports
|May 12, 2016
PubMed
Summary

Posttranslational modifications (PTMs) of islet autoantigens are a new focus in type 1 diabetes (T1D) research. Understanding these PTMs may reveal how the immune system loses tolerance, contributing to T1D development.

Keywords:
Autoimmune diseaseHigh-risk HLAIslet antigensPosttranslational modificationType 1 diabetes

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Area of Science:

  • Immunology
  • Endocrinology
  • Autoimmunity

Background:

  • Type 1 diabetes (T1D) involves autoreactive T cells attacking islet cells.
  • Peripheral tolerance mechanisms normally prevent such attacks.
  • The role of posttranslationally modified (PTM) islet autoantigens in T1D is an emerging area of study.

Purpose of the Study:

  • To review current knowledge on PTM islet autoantigens in T1D.
  • To explore potential new sources of these modified antigens.
  • To discuss the contribution of PTMs to the development and progression of T1D.

Main Methods:

  • Literature review of PTMs in T1D.
  • Analysis of current understanding of PTM antigen identification.
  • Discussion of mechanisms of neo-autoantigen generation.

Main Results:

  • PTM islet autoantigens represent a potential trigger for autoimmunity, as the immune system may be ignorant rather than tolerant to them.
  • Few PTM antigens are currently identified in T1D, but methods for discovery are advancing.
  • PTMs offer a novel perspective on the breakdown of peripheral tolerance in T1D.

Conclusions:

  • Posttranslational modifications of islet autoantigens are a critical, yet understudied, factor in T1D pathogenesis.
  • Further research into PTMs and neo-autoantigens is essential for understanding and potentially treating T1D.
  • Identifying and characterizing novel PTM antigens could lead to new therapeutic strategies for type 1 diabetes.