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

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 <i>CTSH</i> and <i>CTSZ</i>, encoding cathepsins H and Z. These findings were validated using a publicly available independent dataset comprising transcriptomes from fresh muscle tissue samples. <i>NT5C1A</i> 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.