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

• Published in: Arthritis research & therapy Vol. 20; no. 1; p. 194
• Main Authors: Chanouzas, Dimitrios, Sagmeister, Michael, Dyall, Lovesh, Sharp, Phoebe, Powley, Lucy, Johal, Serena, Bowen, Jessica, Nightingale, Peter, Ferro, Charles J, Morgan, Matthew D, Moss, Paul, Harper, Lorraine
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 29.08.2018; BioMed Central; BMC
• Subjects: Aged; ANCA; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis - blood; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis - diagnosis; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis - immunology; Antigens; Arterial stiffness; Arthritis; Atherosclerosis; Cardiovascular disease; Care and treatment; Cohort Studies; Complications and side effects; Cytomegalovirus; Cytomegalovirus - immunology; Cytomegalovirus infections; Cytomegalovirus Infections - blood; Cytomegalovirus Infections - diagnosis; Cytomegalovirus Infections - immunology; Cytotoxicity; Development and progression; Endothelium; Endothelium, Vascular - immunology; Endothelium, Vascular - metabolism; Endothelium, Vascular - virology; Female; Gene expression; Genetic aspects; Genotype & phenotype; Health aspects; Health risk assessment; Hepatitis; Humans; Immune response; Immunity, Cellular - physiology; Infections; Inflammation; Lymphocytes; Male; Middle Aged; Mortality; Phenotypes; Pulse Wave Analysis - methods; Rheumatoid arthritis; T cells; TNF inhibitors; Tumor necrosis factor-TNF; Vascular Stiffness - physiology; Vasculitis; United Kingdom > UK; Cytomegalovirus; Vasculitis; Arterial stiffness; ANCA; Cardiovascular disease; Inflammation; T cells
• ISSN: 1478-6362; 1478-6354; 1478-6362
• DOI: 10.1186/s13075-018-1695-8

Cardiovascular disease is a leading cause of death in ANCA-associated vasculitis (AAV). An expansion of CD4 CD28 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 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. CD4 CD28 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 T cells. Arterial stiffness was measured by carotid-to-femoral pulse wave velocity (PWV) in patients with AAV. CD4 CD28 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 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 T-cell subset was independently linked to increased PWV in AAV (0.66 m/s increase per 10% increase in CD4 CD28 cells, 95% confidence interval 0.13-1.19; P = 0.016). The host cellular immune response to CMV leads to the expansion of cytotoxic CD4 CD28 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.