Muscle & nerve · 2018
Mutated cancer autoantigen implicated cause of paraneoplastic myasthenia gravis.
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Zekeridou Anastasia, Griesmann Guy E, Lennon Vanda A
Аннотация
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.
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.