TNFA and TNFB polymorphisms in myasthenia gravis

Background: Tumor necrosis factor (TNF) alpha and TNF-beta are proinflammat ory cytokines thought to be involved in the pathogenesis of myasthenia grav is (MG). Objective: To examine whether TNF polymorphisms are associated with MG, MG subgroups, and the presence of titin and ryanodine-receptor antibodies. Patients and Methods: We did genotyping on 30 patients with MG and 92 healt hy blood donors for 2 biallelic TNFA polymorphisms (G to A at positions -23 8 and -308) and 1 TNFB polymorphism (NcoI digestive site) using methods bas ed on the polymerase chain reaction. Results: Patients with thymoma were typically homozygous for both the TNFA* T1 and the TNFB*2 alleles, but patients having an early onset of MG without thymoma were carriers of the TNFA*T2 and TNFB*1 alleles. Patients without thymoma who had the titin antibody had the same high frequency of TNFA*T1 a nd TNFB*2 as patients with thymoma, whereas patients without the titin anti body carried the same allele, TNFA*T2 and TNFB*1, regardless of age and thy mic disease. No association was found with acetylcholine-receptor levels or disease severity for any of the TNFA or TNFB polymorphisms. Conclusion: Patients having MG, including those with thymoma, who have the titin antibody are most often homozygous for the TNFA*T1 and TNFB*2 alleles , whereas the presence of the TNFA*T2 and TNFB*1 alleles correlates with ea rly-onset MG and the absence of titin antibodies.