title: Preferential expression of AChR epsilon-subunit in thymomas from patients with myasthenia gravis.
abstract: The role of antigen expression by thymomas in myasthenia gravis (MG) is not clear. Previous reports of acetylcholine receptor (AChR) mRNA expression by the highly sensitive reverse transcription-polymerase chain reactions (RT-PCR) produced varying results. To try to clarify this issue, we first used RT-PCR but then turned to the more accurate and quantitative RNase protection assays (RPA) to assess AChR subunit mRNA expression in thymomas from 25 patients (22 with MG). By RT-PCR, all five AChR subunits could be detected in many thymomas. However, by RPA, the mRNA for the adult-specific AChR epsilon-subunit was found in 13/25 (52%) thymomas, but not mRNA for the other subunits. AChR epsilon-subunit was more frequently detected in thymomas of A or AB histology (WHO classification) than those with B1-B3 histology. Overall, 6/6 with thymomas of A or AB histology were positive compared with only 8/19 with B histology (p=0.02). Autoantibodies in the two patients with the highest levels of epsilon-subunit mRNA bound better to adult (alpha(2)betadeltaepsilon) AChR than to fetal (alpha(2)betadeltagamma) AChR, whereas the other sera bound better to fetal AChR. The greater abundance of mRNA for AChR epsilon-subunit than for other subunits suggests that the AChR epsilon-subunit may play a distinctive role in autosensitization in MG-associated thymomas, particularly those of type A or AB.
authors.affiliation: Neurosciences Group, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK.
authors.forename: Calman A
authors.initials: CA
authors.lastname: Maclennan
authors.forename: Angela
authors.initials: A
authors.lastname: Vincent
authors.forename: Alexander
authors.initials: A
authors.lastname: Marx
authors.forename: Nicholas
authors.initials: N
authors.lastname: Willcox
authors.forename: Nils Eric
authors.initials: NE
authors.lastname: Gilhus
authors.forename: John
authors.initials: J
authors.lastname: Newsom-Davis
authors.forename: David
authors.initials: D
authors.lastname: Beeson
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood; D005260:Female; D015870:Gene Expression / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009157:Myasthenia Gravis / Q000150:complications*; D012333:RNA, Messenger / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D013934:Thymectomy / Q000379:methods; D013945:Thymoma / Q000150:complications* / Q000276:immunology / Q000378:metabolism* / Q000601:surgery; D013953:Thymus Neoplasms / Q000150:complications / Q000378:metabolism* / Q000601:surgery
chemical_list: D001323:Autoantibodies; C504423:CHRNE protein, human; D012333:RNA, Messenger; D011978:Receptors, Nicotinic