Review articleCellular and molecular mechanisms of immune dysregulation and autoimmunity

- Primary immunodeficiency disorders (PID) are frequently complicated by autoimmune and inflammatory conditions.
- Disease of immune dysregulation have improved our knowledge of the pathways that drive autoimmunity in PIDs.
- A number of heritable immune dysregulatory diseases arise from defects which affect Treg cell development, function, or both.
- These consist of immune dysregulation polyendocrinopathy enteropathy X-linked syndrome (IPEX) and IPEX-like disorders.

Primary immunodeficiencies (PIDs) constitute a large group of rare disorders that affect the function of the immune system. A specific group of PIDs entitled “diseases of immune dysregulation” are developed due to mutation in the genes which have critical roles in the regulation of immune responses and immunological tolerance. This group of PID patients develop autoimmune and inflammatory disorders as a result of their impaired immunity, therefore they could be considered as a model for analyzing the link between immune dysregulation and autoimmunity. In this article, our aim is to describe the function of the mutated gene, the molecular and cellular mechanisms underlying the immune dysregulation and review the literature in regard with the reported autoimmune disorders in the main types of immunodysregulatory diseases including genetic defects of regulatory T cells, familial hemophagocytic lymphohistiocytosis syndromes, autoimmunity without lymphoproliferation, autoimmune lymphoproliferative syndrome, immune dysregulation with colitis, and type 1 interferonopathies.