Rare autoimmune disorders with Mendelian inheritance

Autoimmunity. 2016 Aug;49(5):285-97. doi: 10.1080/08916934.2016.1183658. Epub 2016 May 20.


Autoimmune diseases represent a heterogeneous group of common disorders defined by complex trait genetics and environmental effects. The genetic variants usually align in immune and metabolic pathways that affect cell survival or apoptosis and modulate leukocyte function. Nevertheless, the exact triggers of disease development remain poorly understood and the current therapeutic interventions only modify the disease course. Both the prevention and the cure of autoimmune disorders are beyond our present medical capabilities. In contrast, a growing number of single gene autoimmune disorders have also been identified and characterized in the last few decades. Mutations and other gene alterations exert significant effects in these conditions, and often affect genes involved in central or peripheral immunologic tolerance induction. Even though a single genetic abnormality may be the disease trigger, it usually upsets a number of interactions among immune cells, and the biological developments of these monogenic disorders are also complex. Nevertheless, identification of the triggering molecular abnormalities greatly contributes to our understanding of the pathogenesis of autoimmunity and facilitates the development of newer and more effective treatment strategies.

Keywords: Autoimmune disorders; genetics; pathogenesis; rare disorders; tolerance.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autoimmune Diseases / genetics*
  • Autoimmune Diseases / immunology*
  • Autoimmune Diseases / metabolism
  • Autoimmunity / genetics*
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Humans
  • Immune Tolerance / genetics
  • Inheritance Patterns*
  • Rare Diseases*
  • Signal Transduction
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism