Anti-Valosin-Containing Protein (VCP/p97) Autoantibodies in Inclusion Body Myositis and Other Inflammatory Myopathies

Area of Science:

• Immunology
• Neurology
• Autoimmunity

Background:

• Valosin-containing protein (VCP) mutations are linked to hereditary inclusion body myositis (IBM).
• VCP presence in rimmed vacuoles of sporadic IBM (sIBM) muscle biopsies suggests a role in the disease.
• Autoantibodies to VCP have not been previously reported in sIBM or other inflammatory myopathies (IIMs).

Purpose of the Study:

• To investigate the frequency of anti-VCP antibodies in sIBM and other IIMs.
• To determine the clinical significance of anti-VCP antibodies in sIBM.
• To explore the potential of anti-VCP as a biomarker for sIBM.

Main Methods:

• Sera from 73 sIBM patients and 383 controls (including IIM, JDM, JIA, PBC, SACs, and HCs) were analyzed.
• Immunoglobulin G (IgG) antibodies to VCP were detected using addressable laser bead immunoassay.
• Full-length recombinant human VCP protein was used for antibody detection.

Main Results:

• Anti-VCP antibodies were found in 26.0% of sIBM patients.
• The frequency of anti-VCP antibodies in disease controls was 15.0%, 1.6% in similarly aged controls (SACs), and 0% in healthy controls (HCs).
• Anti-VCP demonstrated 26.0% sensitivity, 87.2% specificity, 28.4% positive predictive value, and 85.9% negative predictive value for sIBM.

Conclusions:

• Anti-VCP antibodies have low sensitivity and moderate specificity for sIBM.
• Anti-VCP antibodies may help address the diagnostic challenge in seronegative sIBM cases.
• Further research is warranted to establish anti-VCP as a clinically valuable biomarker for specific sIBM phenotypes.