Tumour necrosis factor-α polymorphism and secretion in myasthenia gravis

Abstract

The mechanism behind the association between MHC genes and myasthenia gravis (MG) is not fully understood. In the present study we studied the associations with polymorphisms at HLA-DR3, HLA-B8 and TNF-α genes in Swedish patients and healthy individuals. The TNF-α-308 allele 2 was associated with female patients having disease onset before the age 40 and with thymic hyperplasia. Analysis of strongest associations between MG and alleles close to TNF-α indicated that the association of TNF-α was possibly stronger than for HLA-DR3 and nearly the same as for HLA-B8. Peripheral blood mononuclear cells from patients positive for TNF-α -308 allele 2 had higher secretion of TNF-α when stimulated by anti-CD3 antibodies. Our results indicate that a subgroup of MG patients who have been previously shown to be associated with MHC genes may have a higher inducible TNF-α level in vivo, thus resulting the pathological changes in the thymus and the early onset of MG.