Mutated cancer autoantigen implicated cause of paraneoplastic myasthenia gravis. Issue 4 (23rd August 2018)

• Record Type: Journal Article
• Authors: Zekeridou, Anastasia; Griesmann, Guy E.; Lennon, Vanda A.
• Is Part Of: Muscle & nerve. Volume 58:Issue 4(2018)
• Page Start: 600
• Page End: 604
• Publication Date: 2018-08-23
• Subjects: cancer neoantigen -- lung cancer -- muscle acetylcholine receptor autoantibody -- onconeural antigens -- paraneoplastic autoimmunity -- sensory neuronopathy; Neuromuscular diseases -- Periodicals; Muscles -- Periodicals; Nerves -- Periodicals; 616.74
• DOI: 10.1002/mus.26166
• Languages: English
• ISSNs: 0148-639X

Abstract

ABSTRACT: Introduction : Antitumor immune responses are postulated to initiate paraneoplastic neurological disorders when proteins that are normally restricted to neural cells are expressed as oncoproteins. Mutated oncopeptides could bypass self‐tolerant T cells to activate cytotoxic effector T lymphocytes and requisite helper T lymphocytes to stimulate autoantibody production by B lymphocytes. Methods : We investigated muscle‐type nicotinic acetylcholine receptor (AChR) antigen expression at transcriptional and protein levels in a small‐cell lung cancer line (SCLC) established from a patient with AChR‐immunoglobulin G (IgG)‐positive myasthenia gravis. Results : We identified messenger RNA transcripts encoding the 2 AChR α1‐subunit isoforms and 7 alternative‐splicing products, 3 of which yielded premature stop codons. Despite detecting native muscle‐type AChR pentamers in the tumor, we did not identify mutant α1‐peptides. However, we found α1‐subunit‐derived peptides bound to tumor major histocompatibility complex (MHC)1‐protein. In a control SCLC from an antineuronal nuclear autoantibody, type 1 (anti‐Hu)‐IgG‐positive patient, we identified MHC1‐complexed Hu protein‐derived peptides but not AChR peptides. Discussion : Our findings support onconeural protein products as pertinent immunogens initiating paraneoplastic neurological autoimmunity. Muscle Nerve 58 : 600–604, 2018