T-cell recognition of acetylcholine receptor provides a reliable means for monitoring autoimmunity to acetylcholine receptor in antibody-negative myasthenia gravis patients

Abstract

Myasthenia gravis (MG) is an autoimmune disease usually associated with autoantibodies (auto-Abs) against nicotinic acetylcholine receptor (AChR). Some MG patients appear negative for anti-AChR Abs (seronegative), and a fraction of these have auto-Abs against muscle-specific kinase. The remaining patients, although displaying MG symptoms, show no detectable auto-Abs. We describe here a possible association of a rare human leukocyte antigen (HLA)-DQ type and AChR Ab-negative MG. We also found that the majority of seronegative patients exhibit an anti-AChR autoimmune T lymphocyte response. We investigated the existence of AChR-reactive T cells in peripheral blood lymphocytes from seronegative patients by their proliferative responses against a mixture of 18 overlapping synthetic peptides encompassing the extracellular part of human AChR α-chain. Of the 10 samples, eight exhibited positive T-cell proliferative responses against the peptide mixtures. The proliferative assay was equally efficient using a mixture of eight peptides frequently recognized by MG T cells. This T-cell proliferative assay should provide a reliable method for monitoring seronegative MG patients.

Keywords::

• Myasthenia gravis
• acetylcholine receptor
• seronegative
• T cells
• synthetic peptides

Acknowledgements

This study was partly supported by grants from the Muscular Dystrophy Association. The support of the Welch Foundation (Grant Q-0007), due to the award to M.Z. Atassi of the Robert A. Welch Chair of Chemistry, is also gratefully acknowledged.

Declaration of Interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.