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; Ferro, Charles J.; Morgan, Matthew D.; Moss, Paul; Harper, Lorraine

doi:10.1186/s13075-018-1695-8

Cited by 26 publications

(20 citation statements)

References 50 publications

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“…The CD28 null subset of T mem has attracted particular interest in the field of atherosclerosis, in particular coronary artery disease 30 , 31 . However, we were unable to identify an association between CD28 null T-cells and cfPWV despite the fact that an association of CD4 CD28 null T-cells with cfPWV was previously reported in patients with ANCA-associated vasculitis (AAV) 41 . It is possible that the presence of autoimmune disease is an important amplifier of this association 50 .…”

Section: Discussioncontrasting

confidence: 70%

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Cytomegalovirus infection is associated with an increase in aortic stiffness in older men which may be mediated in part by CD4 memory T-cells

Kirkham¹,

Pera²,

Simanek³

et al. 2021

Theranostics

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Human Cytomegalovirus (CMV) infection is associated with atherosclerosis, higher cardiovascular disease (CVD) risk, and an increase in memory T-cells (T mem ). T-cells have also been implicated in CVD, independently of CMV infection. To better understand the CMV-associated CVD risk, we examined the association between CMV (IgG) serostatus and central aortic (carotid-to-femoral) pulse wave velocity (cfPWV), an early, independent predictor of CVD. We also investigated if such an association might be reflected by the distribution of T mem and/or other T-cell subsets. Methods: Healthy older volunteers (60-93 years) underwent routine clinical and laboratory evaluation, including assessment of cfPWV in eligible participants. Flow-cytometry was used to assess proportions of memory T-cells, CD28 null T-cells, and CMV-specific T-cells. The following associations were examined; CMV serostatus/cfPWV, CMV serostatus/proportion of T mem , proportion of T mem /cfPWV, CD28 null T-cells/cfPWV, and CMV-specific T-cells/cfPWV. Linear regression models were used to adjust for age, sex, socioeconomic status, smoking, waist-to-hip ratio, cholesterol, and blood pressure as required. Results: Statistically significant positive associations were found (P-values for the fully adjusted models are given); CMV serostatus/cfPWV in men (P ≤ 0.01) but not in women, CMV serostatus/proportions of CD4 T mem in men (P ≤ 0.05) but not in women; proportions of CD4 T mem /cfPWV among CMV seropositive (CMV+) people (P ≤ 0.05) but not CMV seronegative (CMV-) people. Conclusion: CMV infection increases the CVD risk of older men by increasing cfPWV. This may be mediated in part by increased proportions of CD4 T mem , higher numbers of which are found in CMV+ older people and more so among men than women. Given the high prevalence of CMV worldwide, our findings point to a significant global health issue. Novel strategies to mitigate the increased CVD risk associated with CMV may be required.

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Section: Discussioncontrasting

confidence: 70%

“…Prompted by published work 40 , 41 and the known, close link between CMV infection and the proportions of CD28 null T-cells 30 , 31 we also examined correlations between CD28 null T-cell population size and cfPWV. We were, however, unable to confirm a significant effect of CD28 null CD4 or CD8 T-cells on cfPWV.…”

Section: Discussionmentioning

confidence: 99%

Cytomegalovirus infection is associated with an increase in aortic stiffness in older men which may be mediated in part by CD4 memory T-cells

Kirkham¹,

Pera²,

Simanek³

et al. 2021

Theranostics

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“…However, anti-viral medication has proven of more value in people at increased risk of CMV reactivation. In particular, CMV is a significant problem in patients on immune suppression for vasculitis and is associated with increased risk of heterologous infection (86). In this setting the use of valacyclovir for six months did act to completely suppress episodes of viral reactivation.…”

Section: How Can the Clinical Impact Of CMV Infection In Otherwise Hementioning

confidence: 83%

‘From immunosenescence to immune modulation’: a re-appraisal of the role of cytomegalovirus as major regulator of human immune function

Moss

2019

Med Microbiol Immunol

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“…Both T H 1 and T H 17 effector cytokine profiles have been observed in patients with AAV 130,131 , including T H 1 profiles in granulomatous lesions 132 . CD4 + CD28cytotoxic T cells found in the blood of patients with GPA are linked to cytomegalovirus (CMV) infection, which is itself associated with poor AAV outcomes 133 . Furthermore, subclinical CMV infection and reactivation in immunosuppressed patients with AAV may impair immune responses to infection, as the antiviral drug valacyclovir improved vaccine responses in CMV-seropositive patients with AAV 134 .…”

Section: T Cells and Cellular Immunitymentioning

confidence: 99%

ANCA-associated vasculitis

Kitching

Anders

Basu

et al. 2020

Nat Rev Dis Primers

626

507

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The anti-neutrophil cytoplasmic antibody (ANCA)associated vasculitides (AAVs) are diseases characterized by inflammation of blood vessels, endothelial injury and tissue damage. The three types of small-vessel vasculitis, namely granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic GPA (EGPA; previously known as Churg-Strauss syndrome), feature a loss of tolerance to neutrophil primary granule proteins, most often leukocyte proteinase 3 (PR3; also known as myeloblastin) or myeloperoxidase (MPO) (Table 1). The vessels involved in AAV are typically capillaries, arterioles and venules but small arteries and veins may also be affected. Autoimmunity is documented clinically by serum ANCAs to PR3 (PR3-ANCA) or MPO (MPO-ANCA), which are generally associated with the main syndromic AAV presentations (box 1). AAVs collectively represent one of several types of autoimmune vasculitis (Fig. 1). GPA and MPA can involve small blood vessels in any organ or tissue but commonly affect the upper and lower respiratory tract and the kidneys (box 2). Patients with AAV typically present with severe organ-threatening or life-threatening disease, although less severe presentations also occur. GPA is predominantly associated with PR3-ANCA and its clinical features typically include sinonasal disease, lower respiratory tract involvement with pulmonary haemorrhage and granulomatous inflammation, and glomerulonephritis. MPA is usually associated with MPO-ANCA and clinical features include more severe renal disease and some of the manifestations of GPA but without granulomatous inflammation. EGPA is characterized by asthma, eosinophilia and, in many (but not all) cases, vasculitis. EGPA is less common than GPA or MPA and, in some cases, is associated with ANCAs, mainly MPO-ANCA (Table 1). Although categorized as a form of AAV, EGPA has less overlap with the other AAVs than that between GPA and MPA with regard to its genetic, pathogenetic, and clinical features and its management and is typically considered a separate entity. Improvements in treatment and prognosis for patients with AAV have resulted from the translation of both preclinical and clinical research findings. Here, we provide an updated overview of the clinical and

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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

Cited by 26 publications

References 50 publications

Cytomegalovirus infection is associated with an increase in aortic stiffness in older men which may be mediated in part by CD4 memory T-cells

Cytomegalovirus infection is associated with an increase in aortic stiffness in older men which may be mediated in part by CD4 memory T-cells

‘From immunosenescence to immune modulation’: a re-appraisal of the role of cytomegalovirus as major regulator of human immune function

ANCA-associated vasculitis

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