Integrating Autophagy and Histochemical Markers in the Diagnosis of Idiopathic Inflammatory Myopathies

: A Comparative Study of Inclusion Body Myositis, Polymyositis and other IIMs

Abstract

This PhD research investigates the role of autophagy and associated markers in the pathogenesis of idiopathic inflammatory myopathies (IIM), specifically Inclusion Body Myositis (IBM), Polymyositis (PM), and Dermatomyositis (DM). Utilizing a multi-faceted approach, the study integrates retrospective clinical data, immunohistochemical staining, and gene expression analysis to examine the differential expression of key autophagic markers, including p62, LC3, and LAMP2, across these myopathic conditions. Contemporary classification recognizes that true PM is a rare entity, with many historical PM diagnoses now considered early-stage IBM or misdiagnoses; as a result, PM is increasingly regarded as a diagnosis of exclusion after other IIM subtypes are ruled out.
Chapter 3 provides a retrospective review of 69 IIM cases, establishing a foundation for understanding clinical and histopathological variation among IBM, PM, and DM. Chapter 4 investigates staining intensity across 28 cases, comparing manual and automated methods to assess differences in marker expression and their implications for accurate IIM diagnosis. In Chapter 5, expression levels of p62, LC3, and LAMP2 are quantified in 20 cases using both QuPath digital image analysis and manual scoring. The results indicate that aberrant autophagic marker expression aligns with dysregulated autophagic pathways in IBM, with potential relevance for diagnostic specificity and therapeutic strategies.
Ethical approval and informed consent were obtained in compliance with NRES guidelines, ensuring adherence to ethical and institutional standards. Overall, this research advances understanding of autophagy in IIM and supports the development of standardized diagnostic tools to improve patient outcomes, providing a framework for future translational research.

Date of Award	9 Jan 2026
Original language	English
Awarding Institution	University of Portsmouth
Supervisor	Helen Louise Fillmore (Supervisor) & Clara Limbaeck-Stanic (Supervisor)