**21. Conclusion**

with HLA polymorphisms has confirmed the central role of autoimmunity in the development of AAV. All the three main subtypes mentioned above have been

The role of PTPN22 C1858T in AAV provided the basis for the three main PTPN22 genetic association studies performed so far (**Table 16**). The first, which included a German cohort, showed an association of this variant with the disease; the association was even more significant in the ANCA-positive subgroup [259]. This result has been subsequently replicated in two independent cohorts of British [260] and Italian AAV patients [261]. However, the study on Italian patients showed that the association is restricted to the GPA patients only, as almost similar frequency of the T-allele of PTPN22 C1858T was found in the MPA or the EGPA

Three independent meta-analyses indicated that PTPN22 C1858T polymorphism

GCA is a form of vasculitis. It is very common in elderly people and may cause blindness and stroke [263]. The environmental, infectious, and genetic risk factors have been associated with GCA development; however, the pathogenesis is not clear yet. PTPN22 is a gene of interest which is proposed to be an "archetypal non-HLA autoimmunity gene" [251, 264]. The T-allele of a functional PTPN22 C1858T polymorphism has been reported to be associated with biopsy-proven GCA in Spanish patients (**Table 17**), with supporting data from three replicate Northern European studies [265]. Recently, this observation has been extended with additional patients and controls and studies encompassing European, Scandinavian, UK, and American patients [266], though an earlier report from Spanish patients does not support the potential involvement of PTPN22 gene polymorphism in the sus-

Though Lester et al. [267] could not find any significant difference in the distribution of alleles and genotypes of PTPN22 C1858T polymorphism between patients and control groups, they suggested that there is a significant association between

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

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,

and is called as autoimmune polyendocrine syndrome type II (APS II).

is significantly associated with susceptibility of AAV in Caucasian population

reported to be associated with distinct HLA variants [258].

*The Recent Topics in Genetic Polymorphisms*

patients and controls.

**19. Giant cell arteritis**

ceptibility or clinical expression of GCA [263].

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

the minor allele of PTPN22 C1858T polymorphism and GCA.

[76, 262].

**100**

The PTPN22 C1858T is one of the strongest and most consistent genetic associations with autoimmune diseases. However, available literature on PTPN22 C1858T polymorphism and autoimmune diseases shows ethnic variations. It is conceivable that the relation of any locus with the autoimmune disease will be small as interactions between gene and gene and gene and environment might also be operating. Further well-designed studies from different populations and cohorts to detect small genetic risk will help in drawing better conclusion on the development of autoimmune diseases. Therefore, further genetic studies on patients suffering from various autoimmune diseases from different ethnicities and PTPN22 gene polymorphisms are expected to help better understand the pathogenesis and will contribute to the development of more targeted therapies and biomarkers.

## **Acknowledgements**

Authors wish to thank the MSD administration for facilities and support.
