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Open Access 01-12-2018 | Research article

The host cellular immune response to cytomegalovirus targets the endothelium and is associated with increased arterial stiffness in ANCA-associated vasculitis

Authors: Dimitrios Chanouzas, Michael Sagmeister, Lovesh Dyall, Phoebe Sharp, Lucy Powley, Serena Johal, Jessica Bowen, Peter Nightingale, Charles J. Ferro, Matthew D. Morgan, Paul Moss, Lorraine Harper

Published in: Arthritis Research & Therapy | Issue 1/2018

Abstract

Background

Cardiovascular disease is a leading cause of death in ANCA-associated vasculitis (AAV). An expansion of CD4⁺CD28^null T cells is seen mainly in cytomegalovirus (CMV)-seropositive individuals and has been linked to increased cardiovascular disease risk in other conditions. The aims of this study were to phenotype CD4⁺CD28^null T cells in AAV with respect to their pro-inflammatory capacity and ability to target and damage the endothelium and to investigate their relationship to arterial stiffness, a marker of cardiovascular mortality.

Methods

CD4⁺CD28^null T cells were phenotyped in 53 CMV-seropositive AAV patients in stable remission and 30 age-matched CMV-seropositive healthy volunteers by flow cytometry following stimulation with CMV lysate. The expression of endothelial homing markers and cytotoxic molecules was evaluated in unstimulated CD4⁺CD28^null T cells. Arterial stiffness was measured by carotid-to-femoral pulse wave velocity (PWV) in patients with AAV.

Results

CD4⁺CD28^null T cells were CMV-specific and expressed a T helper 1 (Th1) phenotype with high levels of interferon-gamma (IFN-γ) and tumour necrosis factor-alpha (TNF-α) secretion. They also co-expressed the endothelial homing markers CX3CR1, CD49d and CD11b and cytotoxic molecules perforin and granzyme B. CD4⁺CD28^null T cells were phenotypically similar in patients with AAV and healthy volunteers but their proportion was almost twice as high in patients with AAV (11.3% [3.7–19.7] versus 6.7 [2.4–8.8]; P = 0.022). The size of the CD4⁺CD28^null T-cell subset was independently linked to increased PWV in AAV (0.66 m/s increase per 10% increase in CD4⁺CD28^null cells, 95% confidence interval 0.13–1.19; P = 0.016).

Conclusion

The host cellular immune response to CMV leads to the expansion of cytotoxic CD4⁺CD28^null T cells that express endothelial homing markers and are independently linked to increased arterial stiffness, a marker of cardiovascular mortality. Suppression of CMV in AAV may be of therapeutic value in reducing the risk of cardiovascular disease.

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Title: The host cellular immune response to cytomegalovirus targets the endothelium and is associated with increased arterial stiffness in ANCA-associated vasculitis
Authors: Dimitrios Chanouzas
Michael Sagmeister
Lovesh Dyall
Phoebe Sharp
Lucy Powley
Serena Johal
Jessica Bowen
Peter Nightingale
Charles J. Ferro
Matthew D. Morgan
Paul Moss
Lorraine Harper
Publication date: 01-12-2018
Publisher: BioMed Central
Published in: Arthritis Research & Therapy / Issue 1/2018
Electronic ISSN: 1478-6362
DOI: https://doi.org/10.1186/s13075-018-1695-8

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The host cellular immune response to cytomegalovirus targets the endothelium and is associated with increased arterial stiffness in ANCA-associated vasculitis

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Background

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Results

Conclusion

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