Preferential expression of AChR ε-subunit in thymomas from patients with myasthenia gravis

• Published in: Journal of neuroimmunology 2008-09, Vol.201, p.28-32
• Main Authors: MacLennan, Calman A, Vincent, Angela, Marx, Alexander, Willcox, Nicholas, Gilhus, Nils Eric, Newsom-Davis, John, Beeson, David
• Format: Article
• Language: English
• Subjects: AChR ε-subunit; Adolescent; Adult; Aged; Allergy and Immunology; Autoantibodies - blood; Female; Gene Expression - physiology; Humans; Male; Middle Aged; Myasthenia gravis; Myasthenia Gravis - complications; Neurology; Receptors, Nicotinic - genetics; Receptors, Nicotinic - immunology; Receptors, Nicotinic - metabolism; RNA, Messenger - metabolism; RNase protection; Thymectomy - methods; Thymoma; Thymoma - complications; Thymoma - immunology; Thymoma - metabolism; Thymoma - surgery; Thymus Neoplasms - complications; Thymus Neoplasms - metabolism; Thymus Neoplasms - surgery
• ISSN: 0165-5728; 1872-8421
• DOI: 10.1016/j.jneuroim.2008.06.016

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 ε-subunit was found in 13/25 (52%) thymomas, but not mRNA for the other subunits. AChR ε-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 ε-subunit mRNA bound better to adult (α2 βδε) AChR than to fetal (α2 βδγ) AChR, whereas the other sera bound better to fetal AChR. The greater abundance of mRNA for AChR ε-subunit than for other subunits suggests that the AChR ε-subunit may play a distinctive role in autosensitization in MG-associated thymomas, particularly those of type A or AB.