OBJECTIVES: PTPN22 is involved in T-cell activation and its R620W 
single-nucleotide polymorphism (SNP) has been shown to predispose to different 
autoimmune diseases. The aims of this study were to investigate the role of the 
PTPN22 R620W SNP in conferring susceptibility to the ANCA-associated 
vasculitides (AAVs), and to explore potential associations between the PTPN22 
genotype and the disease manifestations.
METHODS: PTPN22 R620W SNP was genotyped in a cohort of 344 AAV patients [143 
with granulomatosis with polyangiitis (Wegener's) (GPA), 102 with microscopic 
polyangiitis (MPA) and 99 with Churg-Strauss syndrome (CSS)] and in 945 healthy 
controls.
RESULTS: The frequency of the minor allele (620W) was significantly higher in 
GPA patients than in controls [P = 0.005, χ(2 )= 7.858, odds ratio (OR) = 1.91], 
while no statistically significant association was found with MPA or CSS. Among 
GPA patients, the 620W allele was particularly enriched in ANCA-positive 
patients as compared with controls (P = 0.00012, χ(2 )= 14.73, OR = 2.31); a 
particularly marked association was also found with ENT involvement (P = 0.0071, 
χ(2 )= 7.258, OR = 1.98), lung involvement (P = 0.0060, χ(2 )= 7.541, OR = 2.07) 
and skin manifestations of all kinds (P = 0.000047, χ(2 )= 16.567, OR = 3.73).
CONCLUSION: The PTPN22 620W allele confers susceptibility to the development of 
GPA (but not of MPA or CSS), and particularly of its ANCA-positive subset.