Cytomegalovirus modulation of the immune system in ANCA associated vasculitis

Chanouzas, Dimitrios (2017). Cytomegalovirus modulation of the immune system in ANCA associated vasculitis. University of Birmingham. Ph.D.

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Abstract

Infection and cardiovascular disease represent the two most important sources of mortality in ANCA associated vasculitis (AAV). Expansions of CD4+CD28null T-cells that are only present in cytomegalovirus (CMV) positive individuals have previously been associated with increased infection and mortality in AAV, and cardiovascular disease in other inflammatory diseases.

The work described in this thesis examines the hypothesis that subclinical CMV reactivation in AAV drives the expansion of CD4+CD28null T-cells thereby leading to the observed adverse outcomes. To investigate this, a proof of concept clinical trial of 6 months valaciclovir treatment or no additional therapy was designed and implemented in CMV seropositive AAV patients in remission.

Valaciclovir treatment successfully blocked CMV reactivation and in turn this led to a reduction in the proportion of CD4+CD28null T-cells in the treated patients together with favourable changes in other associated CMV induced changes on the immune system. CD4+CD28null T-cells in AAV were identified as Th1, proinflammatory cytotoxic T-cells, able to target endothelial cells and were independently associated with increased arterial stiffness, an established marker of cardiovascular risk.

These findings implicate subclinical CMV reactivation as a potentially reversible cause of vascular pathology in inflammatory disease and open novel therapeutic opportunities.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):