TNFA and TNFB polymorphisms in myasthenia gravis.

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 TNFAT1 and the TNFB2 alleles, but patients having an early onset of MG without thymoma were carriers of the TNFAT2 and TNFB1 alleles. Patients without thymoma who had the titin antibody had the same high frequency of TNFAT1 and TNFB2 as patients with thymoma, whereas patients without the titin antibody carried the same allele, TNFAT2 and TNFB1, 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 TNFAT1 and TNFB2 alleles, whereas the presence of the TNFAT2 and TNFB1 alleles correlates with early-onset MG and the absence of titin antibodies.