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Doctoral Thesis
Characterisation of B cells and antibodies targeting cytosolic 5′-nucleotidase 1A in inclusion body myositis
Doctor of Philosophy (PhD), Murdoch University
2025
Abstract
Inclusion Body Myositis (IBM) is a progressive and debilitating chronic inflammatory myopathy that primarily affects older adults. Its pathogenesis is multifactorial, involving autoimmune mechanisms, muscle degeneration, and mitochondrial dysfunction. According to the latest European Neuromuscular Centre criteria, a definitive diagnosis of IBM still requires a confirmatory muscle biopsy. Antibodies against cytosolic 5′-nucleotidase 1A (anti-cN1A), reported in approximately half of patients with IBM, represent the only serological biomarker currently incorporated into the diagnostic criteria.
Although accumulating evidence implicates anti-cN1A antibodies in IBM pathogenesis, their biological relevance remains unresolved. Their association with disease severity is also contested: some studies link anti-cN1A positivity to a more aggressive clinical phenotype and reduced survival, while others find no such correlation. Given the scarcity of reliable blood biomarkers and the lack of effective treatments in IBM, advancing our understanding of anti-cN1A biology can potentially deliver meaningful benefits for patients.
This thesis explores key questions concerning anti-cN1A antibodies and their role in IBM. Chapter 2 examines genetic susceptibility in a Western Australian cohort of Caucasian patients, assessing associations between human leukocyte antigen alleles and IBM risk, and evaluating whether specific genotypes predispose individuals to anti-cN1A positivity. Chapter 3 investigates the pathogenic potential of anti-cN1A-containing serum using primary human skeletal muscle cell model. Chapter 5 shifts the focus to the B cells that produce these antibodies, characterising the molecular features of their receptors. Finally, Chapter 6 considers the broader implications of these findings for therapeutic development and outlines key directions for future research.
Collectively, the findings presented in this thesis advance our understanding of IBM immunobiology and offer promising avenues for further investigations to improve patient care.
Details
- Title
- Characterisation of B cells and antibodies targeting cytosolic 5′-nucleotidase 1A in inclusion body myositis
- Authors/Creators
- Nataliya Slater
- Contributors
- Merrilee Needham (Supervisor) - Murdoch University, Personalised Medicine CentreJerome Coudert (Supervisor) - Murdoch University, Personalised Medicine CentreTimothy Fairchild (Supervisor) - Murdoch University, School of Allied HealthRakesh Naduvile Veedu (Supervisor) - Murdoch University, Personalised Medicine Centre
- Awarding Institution
- Murdoch University; Doctor of Philosophy (PhD)
- Identifiers
- 991005835758607891
- Murdoch Affiliation
- School of Medical, Molecular and Forensic Sciences; Personalised Medicine Centre
- Resource Type
- Doctoral Thesis
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