The PTPN22 620W allele is a risk factor for Wegener's granulomatosis.
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).


CONCLUSIONS
The PTPN22 620W allele appears to be involved in the pathogenesis of WG, and ANCA positivity seems to be the hallmark.
Jagiello
Peter
P
Ruhr University, Bochum, Germany.
Aries
Peer
P
Arning
Larissa
L
Wagenleiter
Sonja E N
SE
Csernok
Elena
E
Hellmich
Bernhard
B
Gross
Wolfgang L
WL
Epplen
Joerg T
JT
D000483:Alleles; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000276:immunology; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D005838:Genotype; D014890:Granulomatosis with Polyangiitis / Q000453:epidemiology* / Q000235:genetics* / Q000276:immunology; D006801:Humans; D011110:Polymorphism, Genetic; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22; D017027:Protein Tyrosine Phosphatases / Q000235:genetics* / Q000276:immunology; D012307:Risk Factors
D019268:Antibodies, Antineutrophil Cytoplasmic; C516765:PTPN22 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22; D017027:Protein Tyrosine Phosphatases