OBJECTIVE: Analyses of families with multiple autoimmune disorders have revealed 
a functional polymorphism, 620W, in the intracellular tyrosine phosphatase gene 
PTPN22 as a predisposing factor for type 1 diabetes, seropositive rheumatoid 
arthritis, systemic lupus erythematosus, and Hashimoto thyroiditis, and the 
presence of the PTPN22 protein appears to herald the development of 
autoantibodies in these disorders. This study therefore examined whether the 
functionally relevant PTPN22 polymorphism is associated with Wegener's 
granulomatosis (WG).
METHODS: A population-based study was performed for the PTPN22 polymorphism in 
199 patients with WG and in 399 healthy individuals. The R620W variation was 
investigated by simple restriction fragment-length polymorphism analysis.
RESULTS: The PTPN22 620W allele frequency was significantly increased in 
antineutrophil cytoplasmic antibody (ANCA)-positive WG patients compared with 
healthy controls (P < 0.001). The association was particularly striking in 
patients with kidney, lung, eye, and peripheral nervous system involvement 
(i.e., those with generalized WG).
CONCLUSION: The PTPN22 620W allele appears to be involved in the pathogenesis of 
WG, and ANCA positivity seems to be the hallmark.