**16. Behcet's diseases**

BD is characterized by recurrent orogenital ulcers, cutaneous inflammation, and uveitis. It is a chronic autoimmune/inflammatory disorder with typical mucocutaneous and ocular manifestations. It also targets musculoskeletal, nervous, vascular, and gastrointestinal systems [236]. The prevalence of BD varies with geographical locations. It is more prevalent in countries along the silk route, particularly in the East Asia and the Middle East. Prevalence is highest in Turkey, followed by Egypt, Morocco, Iraq, Saudi Arabia, Japan, Iran, Korea, and China [237, 238]. Available reports indicate that autoimmunity, genetic factors, and environmental factors are involved in the pathogenesis of BD; however, the specific etiology remains to be determined [236, 239, 240].

Being an autoimmune disease, BD is considered to be affected by PTPN22 C1858T polymorphism. However, there is no significant association of this gene in susceptibility to BD (**Table 14**). Baranathan et al. [241] suggested that PTPN22 C1858T is inversely associated with BD in the UK population indicating its protective role in BD. However, this does not hold for Middle Eastern patients in whom PTPN22 C1858T expression does not associate with BD, possibly due to a very low prevalence of the polymorphism in this population.

The prevalence of PTPN22 C1858T is very low in the general population, and the absence of any correlation with BD indicates that PTPN22 C1858T polymorphism has a limited role in the pathogenesis of autoimmunity [242]. Recently Ortiz-Fe rnández [243] also could not find any association of PTPN22 C1858T polymorphism with BD in Spanish patients.

## **17. Endometriosis**

Endometriosis is a chronic inflammatory disease and one of the most common benign gynecological disorders. It is a condition in which a tissue that is histologically similar to the endometrium, with glands and/or stroma, grows outside the uterine cavity [244]. It presents a multisystem involvement affecting several

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

organs, most commonly in the peritoneum and pelvis, especially the ovaries, and less often in the rectovaginal septum. This results in pelvic pain, dysmenorrhea, and infertility [245].

Although various hypotheses have been proposed to explain the etiology of endometriosis, the explanation of symptoms and presence of ectopic endometrial tissue and stroma at various sites is not very clear [246].

The etiology of endometriosis is complex and characterized by genetic and environmental factors similar to other autoimmune diseases. The immunological changes such as an increase in the number and cytotoxicity of macrophages, increase in the activity of B lymphocytes, abnormalities in the functions and concentrations of B and T lymphocytes, and reduction in the number or the activity of natural killer cells have been indicated in endometriosis. Anti-endometrial and antiovary antibodies have been also found in endometriosis [247]. As genetic factors and immunological predispositions are involved in the etiology of the disease, therefore the variants of genes associated with autoimmune diseases are possible candidates for endometriosis development [247]. PTPN22 C1858T polymorphism and its association with endometriosis have been studied in only three populations (Brazilian, Italian, and Polish) so far (**Table 15**).

The PTPN22 C1858T polymorphism has been reported to be associated with altered risk of endometriosis in Italian and Brazilian populations, but no significant association was found in Polish patients. However, on exploratory analyses Płoski et al. [248] suggested that the T-allele and the TT genotype may be associated with the prevalence of double positivity for antinuclear antibody (ANA) and anticardiolipin autoantibody (ACA).

A meta-analysis showed overall increased risk associations of up to 5.6-fold in endometriosis. In the presence of endometriosis, the PTPN22 C1858T polymorphism may cooperate with clinical and genetic factors to influence the course of disease and immune reactions. These cooperative interactions could result in a statistical association between PTPN22 C1858T and endometriosis [246].

The lymphoid tyrosine phosphatase enzyme is encoded by *PTPN22* gene and is a regulator of signaling through the T-cell receptor and forms a complex with the kinase Csk in T cells. The variant of PTPN22 C1858T polymorphism does not bind kinases properly and results in a gain-of-function enzyme [246, 249, 250]. The increased inhibition of T-cell receptor signaling caused by the PTPN22 C1858T polymorphism could predispose toward autoimmunity, either by affecting the thymic deletion of autoreactive T cells or by affecting the development or function of peripheral regulatory T cells [251].
