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.
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.
| Original language | English |
|---|---|
| Article number | 194 |
| Pages (from-to) | 194 |
| Journal | Arthritis Research & Therapy |
| Volume | 20 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 29 Aug 2018 |
Keywords
- ANCA
- vasculitis
- cytomegalovirus
- inflammation
- t-cells
- arterial stiffness
- cardiovascular disease
Access to Document
- Chanouzas_et_al_The_host_cellular_Arthritis_Research_&_Therapy_2018
Checked for eligibility 12/10/2018 https://doi.org/10.1186/s13075-018-1695-8