IPEX Syndrome and IPEX-Related Disorders

Congenital immune disorders due to immune dysregulation usually present with multi-organ autoimmune manifestations, and recent genetic and molecular diagnosis techniques have deeply implemented the identification of new monogenic defects leading to an altered immune homeostasis. Regulatory T cells (Tregs) play an essential role in controlling immune response, and mutations affecting the transcription factor FOXP3 cause immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome. Strikingly, similar clinical phenotypes resemble IPEX but due to distinct molecular defects have been identified and classified as IPEX-related disorders. These are associated to altered expression of a plethora of factors, either pivotal for Tregs biology or Tregs unrelated, and acting at different levels during immune response regulation. The clinical similarities and differences between these inborn errors of immunity, along with their molecular cause, diagnosis, and treatment options, will be discussed.