title: Tumour necrosis factor-alpha 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-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 thymic hyperplasia. Analysis of strongest associations between MG and alleles close to TNF-alpha indicated that the association of TNF-alpha was possibly stronger than for HLA-DR3 and nearly the same as for HLA-B8. Peripheral blood mononuclear cells from patients positive for TNF-alpha -308 allele 2 had higher secretion of TNF-alpha 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-alpha level in vivo, thus resulting the pathological changes in the thymus and the early onset of MG.
authors.affiliation: Center for Molecular Medicine, Karolinska Hospital, Karolinska Institute, Stockholm, Sweden.
authors.forename: D R
authors.initials: DR
authors.lastname: Huang
authors.forename: R
authors.initials: R
authors.lastname: Pirskanen
authors.forename: G
authors.initials: G
authors.lastname: Matell
authors.forename: A K
authors.initials: AK
authors.lastname: Lefvert
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000483:Alleles; D017252:CD3 Complex / Q000276:immunology / Q000494:pharmacology; D005260:Female; D015870:Gene Expression / Q000276:immunology; D015795:HLA-B8 Antigen / Q000235:genetics / Q000276:immunology; D015803:HLA-DR3 Antigen / Q000235:genetics / Q000276:immunology; D006650:Histocompatibility Testing; D006801:Humans; D006965:Hyperplasia; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009157:Myasthenia Gravis / Q000235:genetics* / Q000276:immunology*; D009469:Neuromuscular Junction / Q000737:chemistry / Q000276:immunology; D012150:Polymorphism, Restriction Fragment Length; D011978:Receptors, Nicotinic / Q000276:immunology; D013548:Sweden; D013950:Thymus Gland / Q000276:immunology / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000276:immunology / Q000378:metabolism
chemical_list: D017252:CD3 Complex; D015795:HLA-B8 Antigen; D015803:HLA-DR3 Antigen; D011978:Receptors, Nicotinic; D014409:Tumor Necrosis Factor-alpha