Discovering New Diagnostic Protein Markers for Sporadic Inclusion Body Myositis

 

Scientific Study Title:

Sporadic Inclusion Body Myositis Proteomics to Identify Novel Biomarkers (SPIN)

 

Study Start Date:

2022

 

Study End Date:

2024

 

Why Did We Do This Research?

Sporadic inclusion body myositis (sIBM) is a muscle disease that’s hard to diagnose because many patients don’t have clear biomarkers (detectable indicators in their blood). Currently, diagnosis relies on invasive muscle biopsies. Delays in diagnosis can result in patients who have severe disability by the time a diagnosis is made. To improve diagnosis and understanding of sIBM, we used advanced machine learning and mass spectrometry techniques to look for new biomarkers—specific proteins or antibodies that could help identify the disease.

 

What Did We Do?

We tested blood samples from 10 sIBM patients using a special array – HuProtTM – a tool for mapping antigen-specific immunity to find new autoantibodies (immune system proteins that mistakenly attack the body). We analyzed blood and muscle tissue samples from sIBM patients to discover new proteins associated with the disease, using a method called mass spectrometry. We used statistical methods and machine learning to pick out the most important biomarkers that distinguish sIBM from healthy controls. We also explored how these biomarkers might be involved in the disease development process, focusing on immune response, inflammation, and muscle degeneration.

 

What Did We Find?

We identified many new autoantibodies and proteins from the tests. Some key findings include:

  • Immune system changes: Certain markers related to the immune system were found to be different in sIBM patients, such as changes in complement proteins and increased inflammation markers.
  • Muscle function: We found markers related to muscle structure and function that were different in sIBM patients.

We also found that processes like cell death, immune response, and inflammation are more active in sIBM patients compared to healthy controls. There were also changes in how muscle contractions and related processes work in sIBM.

This information may help us diagnose SIBM earlier and improve our understanding of how it develops. These findings need to be tested in more patients before they can be used in clinical practice.

 

What Are the Next Steps?

We are working to confirm our findings by testing the new biomarkers in a larger group of sIBM patients.

 

The Research Team

Principal Investigators:

May Y. Choi, MD, FRCPC, MPH, Research Scientist, Rheumatology, Arthritis Research Canada (University of Calgary)

Antoine Dufour, PhD (University of Calgary)

 

Co-Investigators:

Dr. Mark Tarnopolksy, MD, PhD (McMaster University, Hamilton)

Dr. Valérie Leclair, MD, PhD, FRCPC, Research Scientist, Arthritis Research Canada (McGill University)

Dr. Marie Hudson, MD, MPH, FRCPC, Research Scientist, Arthritis Research Canada (McGill University)

Dr. Ross Mitchell, MSc, PhD (University of Alberta)

Dr. Marvin Fritzler, MD, PhD (University of Calgary)

 

Additional Team Members:

Farbod Modhaddam (University of Calgary)

Katherine A. Buhler (University of Calgary)

Erin Hatcher (McMaster University)

Meifeng Zhang (University of Calgary)

Luiz De Almeida (University of Calgary)

 

Who Funded This Research?

University of Calgary

 

Related Publication:

  1. Moghaddam F, Tarnopolsky M, Leclair V, Hudson M, Mitchell R, Buhler K, Hatcher E, Zhang M, Fritzler M, Dufour A, de Almeida L, Choi M. (2024). Sporadic Inclusion Body Myositis Novel Autoantibody and Biomarker Research Utilizing Proteome Microarray and Mass Spectrometry Proteomics Analysis. 5th Global Conference on Myositis (GCOM), 42, 500 – 501. https://doi.org/https://‍‌‌‌doi.org/10.55563/clinexprheumatol/byxxv1
  2. Moghaddam F, Tarnopolsky M, Leclair V, Hudson M, Mitchell R, Buhler K, Hatcher E, Zhang M, Dufour A, de Almeida L, Fritzler M, Choi M. Sporadic Inclusion Body Myositis Novel Autoantibody and Biomarker Research Utilizing Proteome Microarray and Mass Spectrometry Proteomics Analysis [abstract]. Arthritis Rheumatol. 2024; 76 (suppl 9). https://acrabstracts.org/abstract/sporadic-inclusion-body-myositis-novel-autoantibody-and-biomarker-research-utilizing-proteome-microarray-and-mass-spectrometry-proteomics-analysis/ .