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.
Original language | English (US) |
---|---|
Pages (from-to) | 600-604 |
Number of pages | 5 |
Journal | Muscle and Nerve |
Volume | 58 |
Issue number | 4 |
DOIs | |
State | Published - Oct 2018 |
Keywords
- cancer neoantigen
- lung cancer
- muscle acetylcholine receptor autoantibody
- onconeural antigens
- paraneoplastic autoimmunity
- sensory neuronopathy
ASJC Scopus subject areas
- Physiology
- Clinical Neurology
- Cellular and Molecular Neuroscience
- Physiology (medical)