PTPN22 R620W promotes production of anti-AChR autoantibodies and IL-2 in myasthenia gravis

In order to investigate the potential involvement of PTPN22 R620W in the pathogenesis of myasthenia gravis (MG), we performed a case–control study including 409 Swedish MG patients and 1557 normal controls. The W620 variant was significantly overrepresented in patients (odds ratio, 1.52; 95% confidence interval, 1.21–1.90; p = 0.00027). Incubation of patient (n = 100) derived PBMC cells with the autoantigen, the acetylcholine receptor, resulted in a significantly higher number of cells producing anti-AChR antibodies and IL-2 in W620 carriers, suggesting that PTPN22 W620 may be a loss-of-function variant in MG.