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

## TL;DR

This study explores how serum from patients with inclusion body myositis affects muscle cell gene activity, finding distinct patterns in those with anti-cN1A antibodies.

## Contribution

The study identifies a unique transcriptome signature in myotubes exposed to anti-cN1A-positive IBM serum, suggesting novel disease mechanisms.

## Key findings

- Anti-cN1A-positive serum altered 1126 genes in myotubes, including upregulation of CTSH and CTSZ.
- NT5C1A mRNA was not detected in myotubes, indicating no direct antibody-target interaction.
- Findings were validated using an independent dataset of muscle tissue transcriptomes.

## Abstract

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.