Autoimmunity and Inborn Errors of Immunity: Two Faces of the Same Coin!

Infection and autoimmunity: Patients with IEI are unable to clear infections effectively.The molecular mimicry of the pathogen with human tissues leads to autoreactivity, and the cellular debris which is presented to autoreactive T cells triggers the autoimmune cascade, known as "bystander activation."Also, infections with organisms like Staphylococcus and Mycoplasma produce superantigens which result in nonspecific polyclonal activation of T cells and cytokine production.• Defects in Treg development: T regulatory cells are a subset of T cells that play an important role in tolerance and prevent autoimmunity.The defects in the development of Treg cells are associated with loss of inflammatory control and result in autoimmunity.This has been reported in patients with APECED who have low forkhead box protein P3 (FOXP3), which is important for Treg cell activation and development.Other IEIs associated with autoimmunity and low Treg cells are immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX), CD25 deficiency, DiGeorge syndrome, Wiskott-Aldrich syndrome, CTLA4 deficiency, LRBA deficiency, STAT3 GOF mutations, BACH2 deficiency, CD122 deficiency, DEF6 deficiency, and FERMT1 deficiency (Table 1).Let us discuss a few cases.