Tumour necrosis factor-alpha polymorphism and secretion in myasthenia gravis

The mechanism behind the association between MHC genes and myasthenia gravi s (MG) is not fully understood. In the present study we studied the associa tions with polymorphisms at HLA-DR3, HLA-B8 and TNF-alpha genes in Swedish patients and healthy individuals. The TNF-alpha-308 allele 2 was associated with female patients having disease onset before the age 40 and with thymi c hyperplasia. Analysis of strongest associations between MG and alleles cl ose to TNF-alpha indicated that the association of TNF-alpha was possibly s tronger than for HLA-DR3 and nearly the same as for HLA-B8. Peripheral bloo d mononuclear cells from patients positive for TNF-alpha -308 allele 2 had higher secretion of TNF-alpha when stimulated by anti-CD3 antibodies. Our r esults indicate that a subgroup of MG patients who have been previously sho wn to be associated with MHC genes may have a higher inducible TNF-alpha le vel in vivo, thus resulting the pathological changes in the thymus and the early onset of MG. (C) 1999 Elsevier Science B.V. All rights reserved.