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.
Immunological Research Unit, Centre for Molecular Medicine, Karolinska University Hospital Solna, SE-17176 Stockholm, Sweden.
Ann Kari
AK
Lefvert
Yaofeng
Y
Zhao
Ryan
R
Ramanujam
Shuyang
S
Yu
Ritva
R
Pirskanen
Lennart
L
Hammarström
D000704:Analysis of Variance; D001120:Arginine / Q000235:genetics*; D001323:Autoantibodies / Q000378:metabolism*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D009157:Myasthenia Gravis / Q000235:genetics* / Q000276:immunology; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22 / Q000235:genetics*; D011950:Receptors, Cholinergic / Q000276:immunology*; D013548:Sweden; D014364:Tryptophan / Q000235:genetics*
D001323:Autoantibodies; D007376:Interleukin-2; D011950:Receptors, Cholinergic; D014364:Tryptophan; D001120:Arginine; C516765:PTPN22 protein, human; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22