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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The host cellular immune response to cytomegalovirus targets the endothelium and is associated with increased arterial stiffness in ANCA-associated vasculitis. / Chanouzas, Dimitrios; Sagmeister, Michael; Dyall, Lovesh; Sharp, Phoebe; Powley, Lucy; Johal, Serena; Bowen, Jessica; Nightingale, Peter; Ferro, Charles; Morgan, Matthew; Moss, Paul; Harper, Lorraine.

In: Arthritis Research & Therapy, Vol. 20, No. 1, 194, 29.08.2018, p. 194.

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@article{a6c44b4eadf34369acfbfd254f5f7151,
title = "The host cellular immune response to cytomegalovirus targets the endothelium and is associated with increased arterial stiffness in ANCA-associated vasculitis",
abstract = "Background: Cardiovascular disease is a leading cause of death in ANCA-associated vasculitis (AAV). An expansion of CD4+CD28null T-cells is mainly seen 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+CD28null T-cells in AAV in respect of their proinflammatory capacity and ability to target and damage the endothelium, and investigate their relationship to arterial stiffness, a marker of cardiovascular mortality.Methods: CD4+CD28null 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+CD28null T-cells. Arterial stiffness was measured by carotid-to-femoral pulse wave velocity (PWV) in AAV patients.Results: CD4+CD28null T-cells were CMV-specific and expressed a Th1 phenotype with high levels of IFN- and TNF- secretion. They also co-expressed the endothelial-homing markers CX3CR1, CD49d and CD11b and cytotoxic molecules perforin and granzyme B. CD4+CD28null T-cells were phenotypically similar within AAV and healthy volunteers but their proportion was almost twice as high in AAV patients (11.3% [3.7 – 19.7] versus 6.7 [2.4– 8.8]; p=0.022). The size of the CD4+CD28null T-cell subset was independently linked to increased PWV in AAV (0.66m/s increase per 10% increase in CD4+CD28null cells [95%CI0.13–1.19]; p=0.016).Conclusion: The host cellular immune response to CMV leads to the expansion of cytotoxic CD4+CD28null 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.",
keywords = "ANCA, vasculitis, cytomegalovirus, inflammation, t-cells, arterial stiffness, cardiovascular disease",
author = "Dimitrios Chanouzas and Michael Sagmeister and Lovesh Dyall and Phoebe Sharp and Lucy Powley and Serena Johal and Jessica Bowen and Peter Nightingale and Charles Ferro and Matthew Morgan and Paul Moss and Lorraine Harper",
year = "2018",
month = aug,
day = "29",
doi = "10.1186/s13075-018-1695-8",
language = "English",
volume = "20",
pages = "194",
journal = "Arthritis Research & Therapy",
issn = "1478-6354",
publisher = "Springer",
number = "1",

}

RIS

TY - JOUR

T1 - The host cellular immune response to cytomegalovirus targets the endothelium and is associated with increased arterial stiffness in ANCA-associated vasculitis

AU - Chanouzas, Dimitrios

AU - Sagmeister, Michael

AU - Dyall, Lovesh

AU - Sharp, Phoebe

AU - Powley, Lucy

AU - Johal, Serena

AU - Bowen, Jessica

AU - Nightingale, Peter

AU - Ferro, Charles

AU - Morgan, Matthew

AU - Moss, Paul

AU - Harper, Lorraine

PY - 2018/8/29

Y1 - 2018/8/29

N2 - Background: Cardiovascular disease is a leading cause of death in ANCA-associated vasculitis (AAV). An expansion of CD4+CD28null T-cells is mainly seen 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+CD28null T-cells in AAV in respect of their proinflammatory capacity and ability to target and damage the endothelium, and investigate their relationship to arterial stiffness, a marker of cardiovascular mortality.Methods: CD4+CD28null 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+CD28null T-cells. Arterial stiffness was measured by carotid-to-femoral pulse wave velocity (PWV) in AAV patients.Results: CD4+CD28null T-cells were CMV-specific and expressed a Th1 phenotype with high levels of IFN- and TNF- secretion. They also co-expressed the endothelial-homing markers CX3CR1, CD49d and CD11b and cytotoxic molecules perforin and granzyme B. CD4+CD28null T-cells were phenotypically similar within AAV and healthy volunteers but their proportion was almost twice as high in AAV patients (11.3% [3.7 – 19.7] versus 6.7 [2.4– 8.8]; p=0.022). The size of the CD4+CD28null T-cell subset was independently linked to increased PWV in AAV (0.66m/s increase per 10% increase in CD4+CD28null cells [95%CI0.13–1.19]; p=0.016).Conclusion: The host cellular immune response to CMV leads to the expansion of cytotoxic CD4+CD28null 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.

AB - Background: Cardiovascular disease is a leading cause of death in ANCA-associated vasculitis (AAV). An expansion of CD4+CD28null T-cells is mainly seen 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+CD28null T-cells in AAV in respect of their proinflammatory capacity and ability to target and damage the endothelium, and investigate their relationship to arterial stiffness, a marker of cardiovascular mortality.Methods: CD4+CD28null 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+CD28null T-cells. Arterial stiffness was measured by carotid-to-femoral pulse wave velocity (PWV) in AAV patients.Results: CD4+CD28null T-cells were CMV-specific and expressed a Th1 phenotype with high levels of IFN- and TNF- secretion. They also co-expressed the endothelial-homing markers CX3CR1, CD49d and CD11b and cytotoxic molecules perforin and granzyme B. CD4+CD28null T-cells were phenotypically similar within AAV and healthy volunteers but their proportion was almost twice as high in AAV patients (11.3% [3.7 – 19.7] versus 6.7 [2.4– 8.8]; p=0.022). The size of the CD4+CD28null T-cell subset was independently linked to increased PWV in AAV (0.66m/s increase per 10% increase in CD4+CD28null cells [95%CI0.13–1.19]; p=0.016).Conclusion: The host cellular immune response to CMV leads to the expansion of cytotoxic CD4+CD28null 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.

KW - ANCA

KW - vasculitis

KW - cytomegalovirus

KW - inflammation

KW - t-cells

KW - arterial stiffness

KW - cardiovascular disease

U2 - 10.1186/s13075-018-1695-8

DO - 10.1186/s13075-018-1695-8

M3 - Article

C2 - 30157919

VL - 20

SP - 194

JO - Arthritis Research & Therapy

JF - Arthritis Research & Therapy

SN - 1478-6354

IS - 1

M1 - 194

ER -