title: Autoimmunity to ryanodine receptor and titin in myasthenia gravis is associated with GM allotypes.
abstract: Myasthenia gravis (MG) is mediated by autoantibodies against the acetylcholine receptor at the muscle endplate. Some MG patients have in addition antibodies (Ab) to the skeletal muscle proteins ryanodine receptor (RyR) and titin. We have examined GM and KM allotypes, RyR and titin Ab in 44 MG patients (37 thymoma patients and 7 non-thymoma, late-onset patients) and 292 non-MG controls to see if GM/KM allotypes associate with differences in autoantibody production. All patients had titin Ab, and 15 thymoma patients had also RyR Ab. The phenotype GM 1, 2, 3 23 5, 21 was significantly increased in the patients with titin Ab compared with the non-MG controls (chi2 = 4.93, p < 0.05). Thymoma patients with RyR Ab had a higher frequency of the GM 3 23 5 phenotype compared with RyR Ab negative patients and controls (chi2 = 7.1, p < 0.05). KM allotypes did not differ between RyR Ab positive or titin Ab positive patients and controls. GM phenotypes may thus be associated with an autoimmune response against the muscle proteins titin and RyR in MG patients.
authors.affiliation: Department of Neurology, University of Bergen, Norway.
authors.forename: G O
authors.initials: GO
authors.lastname: Skeie
authors.forename: J P
authors.initials: JP
authors.lastname: Pandey
authors.forename: J A
authors.initials: JA
authors.lastname: Aarli
authors.forename: N E
authors.initials: NE
authors.lastname: Gilhus
mesh_terms: D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood*; D015153:Blotting, Western; D002148:Calmodulin-Binding Proteins / Q000032:analysis / Q000276:immunology; D002352:Carrier Proteins / Q000032:analysis / Q000276:immunology; D064211:Connectin; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005858:Germany; D006239:Haplotypes; D006386:Hemagglutination Tests; D006801:Humans; D007129:Immunoglobulin Gm Allotypes / Q000097:blood / Q000145:classification*; D008297:Male; D008565:Membrane Proteins / Q000032:analysis / Q000276:immunology; D008875:Middle Aged; D009124:Muscle Proteins / Q000032:analysis / Q000276:immunology*; D009157:Myasthenia Gravis / Q000276:immunology*; D009664:Norway; D010641:Phenotype; D011494:Protein Kinases / Q000032:analysis / Q000276:immunology*; D019837:Ryanodine Receptor Calcium Release Channel / Q000032:analysis / Q000276:immunology*; D013945:Thymoma / Q000276:immunology; D013953:Thymus Neoplasms / Q000276:immunology
chemical_list: D001323:Autoantibodies; D002148:Calmodulin-Binding Proteins; D002352:Carrier Proteins; D064211:Connectin; D007129:Immunoglobulin Gm Allotypes; D008565:Membrane Proteins; D009124:Muscle Proteins; D019837:Ryanodine Receptor Calcium Release Channel; C577285:TTN protein, human; D011494:Protein Kinases