Severe infection in ANCA-associated vasculitis: Incidence, prognostic factors and prediction

Rutherford, Matthew Alexander (2025) Severe infection in ANCA-associated vasculitis: Incidence, prognostic factors and prediction. PhD thesis, University of Glasgow.

Abstract

Introduction
Individuals with ANCA-associated vasculitis (AAV) are at high risk of severe infections. Using prognosis research methodology, this thesis will explore the incidence of severe infection, examine glucocorticoid exposure as a prognostic marker for severe infection and will develop prognostic models to predict severe infection events: the occurrence of first severe infection after diagnosis and early mortality following a severe infection event. Subsequent chapters will examine Covid-19 in AAV patients including prognostic factors for severe disease and the impact of SARS-CoV-2 vaccination in AAV patients treated with rituximab.

Methods
Diverse datasets were utilised to address the thesis aims. Novel semantic web technology was deployed to federate multiple European AAV registries to determine severe infection incidence. Data linkage was used to develop a large AAV dataset using national Scottish routinely-collected health data for the severe infection prognostic marker and prognostic modelling studies. A binational cohort of AAV patients with Covid-19 was developed through the contribution of vasculitis clinicians throughout the UK and Ireland. SARS-CoV-2 vaccination data was derived from the AAV sub-group of the UK-wide multicentre multi-disease OCTAVE study of immunosuppressed individuals. For the prognostic modelling studies, modern prediction methodologies were applied.

Results
Severe infection incidence was high, especially in the first year after diagnosis. Glucocorticoid exposure thresholds above 10 mg daily all had a substantial positive association with severe infection. Multivariable models were developed with good predictive ability for both severe infection events and early mortality following severe infection. Prognostic factors for severe Covid-19 included immunosuppressive agents. The humoral immune response to SARS-CoV-2 vaccination was severely attenuated in AAV patients compared to controls.

Discussion
Through applying prognosis research methodology, this thesis quantified the incidence of severe infection, identified prognostic factors and developed prognostic models for severe infection in individuals with AAV. Prognostic factors relating to Covid-19 were determined.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Additional Information: Supported by funding from Vifor Pharma.
• Subjects: Q Science > QR Microbiology > QR180 Immunology
• Colleges/Schools: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Supervisor's Name: Basu, Professor Neil
• Date of Award: 2025
• Depositing User: Theses Team
• Unique ID: glathesis:2025-85034
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 10 Apr 2025 13:30
• Last Modified: 10 Apr 2025 14:14
• Thesis DOI: 10.5525/gla.thesis.85034
• URI: https://theses.gla.ac.uk/id/eprint/85034