Programmed cell death ligand 1 expression is upregulated in the skeletal muscle of patients with myasthenia gravis

2018 ◽  
Vol 325 ◽  
pp. 74-78 ◽  
Author(s):  
Kazuo Iwasa ◽  
Hiroaki Yoshikawa ◽  
Yutaka Furukawa ◽  
Masahito Yamada
Keyword(s):  
Skeletal Muscle ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Myasthenia Gravis

Myasthenia Gravis Associated With Programmed Death-1 (PD-1) Receptor Inhibitor Pembrolizumab: A 40-day Case Report

2020 ◽  
pp. 089719002097075
Author(s):  
Aidan S. Ziobro ◽  
Reid L. LaPlante ◽  
Shayna R. DeMari ◽  
Larissa M. Clark ◽  
David J. Kingsley ◽  
...  
Keyword(s):  
Cell Death ◽  
Case Report ◽  
Programmed Cell Death ◽  
Adverse Events ◽  
Myasthenia Gravis ◽  
Cardiopulmonary Arrest ◽  
Palliative Therapy ◽  
Treatment Modalities ◽  
Duration Of Treatment ◽  
Serious Adverse Events

Purpose: This case report describes myasthenia gravis-like symptoms after treatment with a programmed cell death 1 inhibitor, pembrolizumab, the treatment modalities utilized, and associated patient outcomes. Summary: A 76-year old male treated with pembrolizumab for palliative therapy for metastatic melanoma presented with increasing weakness, neck pain, diplopia in the left eye, abducens palsy, periorbital edema, and decreased appetite. The patient was diagnosed with acetylcholine receptor antibody (AChR) negative myasthenia gravis. The patient was started on prednisone 1 mg/kg/day, followed by pyridostigmine 60 mg by mouth 3 times a day, and IVIg for 5 days. Due to minor improvements in myasthenia gravis symptoms, 5 cycles of plasmapheresis were ordered. The patient was successfully treated for aspiration pneumonia after cardiopulmonary arrest. On day 28, the patient was diagnosed with ventilator associated pneumonia and received appropriate therapy. Due to ICU agitation and delirium, VAP, and long duration of treatment, the patient requested withdrawal of care and passed. Conclusion: Programmed cell death inhibitors, such as pembrolizumab, can provide great benefit to patients but can also be associated with rare but serious adverse events. With new reports of MG after use, providers should continually weigh the benefits versus harm in using these products and monitor patients closely for such adverse events.

Programmed cell death in skeletal muscle

1998 ◽  
Vol 26 (3) ◽  
pp. S259-S259 ◽  
Author(s):  
Antonia Maglara ◽  
Malcolm J Jackson ◽  
Anne McArdle
Keyword(s):  
Skeletal Muscle ◽  
Cell Death ◽  
Programmed Cell Death

scholarly journals Expression of a cell death marker (clusterin) in muscle target fibers

1993 ◽  
Vol 51 (3) ◽  
pp. 371-376 ◽  
Author(s):  
Acary Souza Bulle Oliveira ◽  
Massimo Corbo ◽  
Greg Duigou ◽  
Alberto Alain Gabbai ◽  
Arthur P. Hays
Keyword(s):  
Skeletal Muscle ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Muscle Biopsy ◽  
Neuromuscular Disorders ◽  
High Concentration ◽  
A Cell ◽  
Target Fibers ◽  
First Time

We report, for the first time, the expression of immunoractivity to clusterin in skeletal muscle. Clusterin, a protein probably related to the process of programmed cell death (apoptosis), was specifically very highly expressed in target fibers. All target fibers found in 50 muscle biopsy samples from a variety of neuromuscular disorders expressed a high concentration of clusterin in the middle of the targets. Clusterin was not expressed in any targetoid fibers or cores. Acute denervation, where targets are mostly seen, may be the beginning of apoptosis. Hence our findings support the concept that targets are harbingers of acute denervation.

scholarly journals Acheron/Larp6 Is a Survival Protein That Protects Skeletal Muscle From Programmed Cell Death During Development

2020 ◽  
Vol 8 ◽  
Author(s):  
Ankur Sheel ◽  
Rong Shao ◽  
Christine Brown ◽  
Joanne Johnson ◽  
Alexandra Hamilton ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Cell Death ◽  
Programmed Cell Death

scholarly journals PD1 pathway in immune-mediated myopathies

2019 ◽  
Vol 6 (3) ◽  
pp. e558 ◽  
Author(s):  
Samuel Knauss ◽  
Corinna Preusse ◽  
Yves Allenbach ◽  
Sarah Leonard-Louis ◽  
Mehdi Touat ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
T Cells ◽  
Cell Death ◽  
T Cell ◽  
Programmed Cell Death ◽  
T Cell Exhaustion ◽  
Cell Exhaustion ◽  
Immune Mediated ◽  
Muscle Biopsies ◽  
Cell Death Protein

ObjectiveTo investigate the relevance of dysfunctional T cells in immune-mediated myopathies. We analyzed T-cell exhaustion and senescence, in the context of programmed cell death protein 1 (PD1)-related immunity in skeletal muscle biopsies from patients with immune-mediated necrotizing myopathy (IMNM), sporadic inclusion body myositis (sIBM), and myositis induced by immune checkpoint inhibitors (irMyositis).MethodsSkeletal muscle biopsies from 12 patients with IMNM, 7 patients with sIBM, and 8 patients with irMyositis were analyzed by immunostaining and immunofluorescence as well as by quantitative PCR. Eight biopsies from nondisease participants served as controls.ResultsCD3+CD8+ T cells in biopsies from IMNM, sIBM, and irMyositis were largely PD1-positive, while CD68+ macrophages were sparsely positive to the ligand of programmed cell death protein 1 (PD-L1). The sarcolemma of myofibers was PD-L2+ and was colocalized with major histocompatibility complex (MHC) class I. CD68+ macrophages were colocalized with PD-L2. Senescent T cells were strongly enriched in skeletal muscle of sIBM, revealing a distinct immunologic signature. Biopsies from patients with irMyositis showed mild signs of senescence and exhaustion.ConclusionPersistent exposure to antigens in IMNMs and sIBM may lead to T-cell exhaustion, a process controlled by the PD1 receptor and its cognate ligands PD-L1/PD-L2. To our knowledge, these data are the first evidence of presence of dysfunctional T cells and relevance of the PD1 pathway in IMNM, sIBM, and irMyositis. These findings may guide the way to a novel understanding of the immune pathogenesis of immune-mediated myopathies.

Sign in / Sign up

Export Citation Format

Share Document