Altered Transcriptome Signature in Primary Human Myotubes Exposed to Inclusion Body Myositis Serum: A Pilot Case Comparison of Anti-cN1A Positive and Negative Sera

Nataliya Slater; Abha Chopra; Ramesh Ram; Abbie Adams; Frank L. Mastaglia; Merrilee Needham; Jerome D. Coudert

doi:10.3390/muscles4040053

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Altered Transcriptome Signature in Primary Human Myotubes Exposed to Inclusion Body Myositis Serum: A Pilot Case Comparison of Anti-cN1A Positive and Negative Sera

Journal article

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Altered Transcriptome Signature in Primary Human Myotubes Exposed to Inclusion Body Myositis Serum: A Pilot Case Comparison of Anti-cN1A Positive and Negative Sera

Nataliya Slater, Abha Chopra, Ramesh Ram, Abbie Adams, Frank L. Mastaglia, Merrilee Needham and Jerome D. Coudert

Muscles, Vol.4(4), 53

2025

DOI: https://doi.org/10.3390/muscles4040053

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Abstract

inclusionbody myositis

cytosolic 5′-nucleotidase 1A

NT5C1A

anti-cN1A

autoantibodies

primary human myotubes

inflammatory myopathy

Inclusion body myositis (IBM) is a late-onset, treatment-resistant inflammatory myopathy. Approximately half of IBM patients develop autoantibodies against cytosolic 5′-nucleotidase 1A (cN1A), but their role in disease pathogenesis remains unclear. This pilot study examined the effects of anti-cN1A-positive IBM serum on human primary myotubes’ transcriptome profile, using anti-cN1A-negative IBM and healthy sera as controls. Exposure to anti-cN1A-positive serum altered the expression of 1126 genes, with upregulation of adaptive immune response genes, notably CTSH and CTSZ, encoding cathepsins H and Z. These findings were validated using a publicly available independent dataset comprising transcriptomes from fresh muscle tissue samples. NT5C1A mRNA, which encodes cN1A, was not detected in cultured myotubes regardless of the presence of autoantibodies. The findings suggest distinct pathological mechanisms in anti-cN1A-positive IBM, independent of direct antibody-target interactions. The role of cathepsins in IBM pathogenesis warrants further investigation.

Details

Title: Altered Transcriptome Signature in Primary Human Myotubes Exposed to Inclusion Body Myositis Serum: A Pilot Case Comparison of Anti-cN1A Positive and Negative Sera
Authors/Creators: Nataliya Slater - Murdoch University
Abha Chopra - Murdoch University
Ramesh Ram - Murdoch University
Abbie Adams - Murdoch University
Frank L. Mastaglia - Perron Institute for Neurological and Translational Science
Merrilee Needham - Fiona Stanley Hospital
Jerome D. Coudert - The University of Notre Dame Australia
Publication Details: Muscles, Vol.4(4), 53
Publisher: MDPI
Identifiers: 991005830138207891
Murdoch Affiliation: Health Futures Institute; Personalised Medicine Centre
Language: English
Resource Type: Journal article

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