**20. Autoimmune Addison's disease (AAD)**

AAD occurs due to autoimmune destruction of the adrenal cortex. Approximately half of the patients have additional autoimmune components. The prevalence of AAD varies from 110 to 144 cases per million in the developed countries. In adult patients, AAD is the most common etiological form (80%), followed by posttuberculosis AD (10–15%) and vascular, neoplastic, or rare genetic forms (5%) [268]. AAD commonly coexists with thyroid autoimmunity and/or type I diabetes and is called as autoimmune polyendocrine syndrome type II (APS II).

Several genetic determinants have long been suspected to be involved in various autoimmune diseases. PTPN22 C1858T polymorphism has been studied in AAD patients with inconsistent results (**Table 18**). Velaga et al. [151] reported an association for the T-allele in patients from northeast England, whereas Kahles et al. [185] found no association in German patients. This inconsistency may be due to small sample size. The 1858T allele is associated with susceptibility to AAD in Norwegians [269], UK cohort, and the Polish population [270]. Meta-analysis of the results,

*The Protein Tyrosine Phosphatase Non-Receptor Type 22 (PTPN22) Gene Polymorphism… DOI: http://dx.doi.org/10.5772/intechopen.90836*

together with those from three other populations, showed that the 1858T allele is associated with AAD susceptibility.

Confounding factors must be considered particularly when polymorphisms identified in one study cannot be duplicated in a similar ethnic group. One confounding factor is population stratification. This may occur with an unbalanced ethnic admixture.

It is clear that the inheritance of a coding variant of *PTPN22* gene is associated with increased susceptibility to autoimmunity. The mechanism by which the PTPN22 C1858T variant modulates disease risk has been studied. PTPN22 is capable of both enzymatic activities and adaptor functions. It exerts its effects in multiple biochemical pathways and cell types. PTPN22 regulates signaling through both antigen and innate immune receptors. It is involved in the development and activation of lymphocyte, establishment of tolerance, and innate immune cell-mediated host defense and immunoregulation. The PTPN22 C1858T variant protein is involved in the pathogenesis of autoimmunity at multiple levels. The action of PTPN22 C1858T during immature B-cell selection disrupts the establishment of a tolerant B-cell repertoire and alters mature T-cell responsiveness. When an autoimmune attack initiates tissue injury, the TPN22C1858T fosters inflammation by regulating the level of cytokines produced by a myeloid cell.
