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Investigating the immune response to Staphylococcus aureus bloodstream infection in haemodialysis patients

thesis
posted on 13.11.2020, 15:46 by Roisin Connolly
Staphylococcus aureus bloodstream infection (SA-BSI) is a serious and potentially fatal problem in haemodialysis patients. An effective S. aureus vaccine would have significant benefits in this group. Previous antibody-inducing vaccine candidates failed to prevent or attenuate SA-BSI and it is now accepted that next-generation anti- S. aureus vaccines must also induce effective T-cell-mediated immunity. Recent advances have helped to elucidate the role of specific T-cell subsets, notably Th1 and Th17 cells, which coordinate an effective phagocytic response via cytokine production, in the immune response to S. aureus.
Haemodialysis patients are immunocompromised and demonstrate poor responses to many vaccines. They also have specific T-cell defects, which may affect their ability to respond to S. aureus infection and, potentially, a future vaccine. We need a better understanding of T-cell-mediated immunity in these patients, who are important targets for a S. aureus vaccine.
Here, we describe 65 haemodialysis patients, recruited from a population of 151. Just over half were male, the median age was 61 (range 23- 89) and chronic glomerulonephritis and diabetes mellitus were the commonest aetiologies of kidney disease. Proportions of peripheral blood mononuclear cell subsets were determined and S. aureus antigen-specific CD4 cell responses were assessed. In patients with documented previous S. aureus exposure (n=41; 63%), a lower proportion of Th2 cells was observed than in those without. S. aureus antigen-specific Th1 cell proliferation appeared to be higher in patients with documented previous S. aureus exposure than in those without.
In six haemodialysis patients who developed SA-BSI, T-cell responses varied widely; clinical features and infection outcome also differed between patients, but further recruitment is required to demonstrate associations.
This research adds to existing knowledge about the importance of Th1 cells in the immune response to S. aureus and provides novel insights into cell-mediated immunity in haemodialysis patients.

History

First Supervisor

Professor Hilary Humphreys

Second Supervisor

Professor Rachel Mc Loughlin

Comments

A thesis submitted for the degree of Doctor of Medicine from the Royal College of Surgeons in Ireland in 2019.

Published Citation

Connolly R. Investigating the immune response to Staphylococcus aureus bloodstream infection in haemodialysis patients [MD Thesis]. Dublin: Royal College of Surgeons in Ireland; 2019.

Degree Name

Doctor of Medicine (MD)

Date of award

30/11/2019

Programme

  • Doctor of Medicine (MD)