The autoimmunity-related polymorphism PTPN22 1858C/T is associated with anti-titin antibody-positive myasthenia gravis.

Genetic variation in the intracellular tyrosine phosphatase PTPN22 has been recently associated with susceptibility to various autoimmune diseases. Myasthenia gravis (MG) is a complex genetic disease with a distinct clinical and pathological heterogeneity. We conducted a case-control association study for the PTPN22 1858C/T polymorphism in Hungarian and German MG patients (n = 282) and regional controls (n = 379). We detected an association of the PTPN22 1858T allele with MG in the subgroup of nonthymoma patients with anti-titin antibodies present (n = 50; T allele frequency 21% vs 11% in controls; p = 0.005, odds ratio 2.1, 95% confidence interval 1.23-3.58). This overrepresentation was reported independently in both Hungarian and German MG patients compared with regional controls. We conclude that the common autoimmune polymorphism PTPN22 1858C/T may account for disease susceptibility in a subset of nonthymoma MG patients with anti-titin antibodies present.