Background: Tumor necrosis factor (TNF) alpha and TNF-beta are proinflammatory cytokines thought to be involved in the pathogenesis of myasthenia gravis (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 healthy blood donors for 2 biallelic TNFA polymorphisms (G to A at positions -238 and -308) and 1 TNFB polymorphism (NcoI digestive site) using methods based 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 and TNFB*2 as patients with thymoma, whereas patients without the titin antibody carried the same allele, TNFA*T2 and TNFB*1, regardless of age and thymic 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 early-onset MG and the absence of titin antibodies.