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Abstract
BackgroundAccumulating evidence indicates that persistent human cytomegalovirus (HCMV) infection is associated with several health-related adverse outcomes including atherosclerosis and premature mortality in individuals with normal renal function. Patients with end-stage renal disease (ESRD) exhibit impaired immune function and thus may face higher risk of HCMV-related adverse outcomes. Whether the level of anti-HCMV immune response may be associated with the prognosis of hemodialysis patients is unknown.ResultsAmong 412 of the immunity in ESRD study (iESRD study) participants, 408 were HCMV seropositive and were analyzed. Compared to 57 healthy individuals, ESRD patients had higher levels of anti-HCMV IgG. In a multivariate-adjusted logistic regression model, the log level of anti-HCMV IgG was independently associated with prevalent coronary artery disease (OR = 1.93, 95% CI = 1.2~ 3.2, p = 0.01) after adjusting for age, sex, hemoglobin, diabetes, calcium phosphate product and high sensitivity C-reactive protein. Levels of anti-HCMV IgG also positively correlated with both the percentage and absolute number of terminally differentiated CD8+ and CD4+ CD45RA+ CCR7- TEMRA cells, indicating that immunosenescence may participate in the development of coronary artery disease.ConclusionThis is the first study showing that the magnitude of anti-HCMV humoral immune response positively correlates with T cell immunosenescence and coronary artery disease in ESRD patients. The impact of persistent HCMV infection should be further investigated in this special patient population.
Highlights
Accumulating evidence indicates that persistent human cytomegalovirus (HCMV) infection is associated with several health-related adverse outcomes including atherosclerosis and premature mortality in individuals with normal renal function
Elevated HCMV IgG levels is not associated with systemic inflammation in end-stage renal disease (ESRD) Since premature aging and systemic inflammation are important features of ESRD patients [31], we tested the associations between HCMV-specific IgG level with chronological age and circulatory inflammatory markers
We successfully demonstrated the association between higher anti-HCMV IgG titer in ESRD patients and higher risk for CAD, and suggested a potential mechanistic link between subclinical HCMV reactivation, aggravated T cell effector differentiation and coronary artery disease in this patient population
Summary
Accumulating evidence indicates that persistent human cytomegalovirus (HCMV) infection is associated with several health-related adverse outcomes including atherosclerosis and premature mortality in individuals with normal renal function. Patients with end-stage renal disease (ESRD) exhibit impaired immune function and may face higher risk of HCMV-related adverse outcomes. Large-scale epidemiological studies and meta-analysis have suggested an association between HCMV seropositivity and cardiovascular disease [9, 10]. Yang et al Immunity & Ageing (2018) 15:15 infect endothelial cells, which explains why its viral DNA is often found at sites of arterial disease [12]. Several studies based on HCMVspecific IgG titers showed that higher IgG titers against HCMV, but not antibodies against herpes simplex virus 1, are significantly associated with incident coronary artery events [15, 16]. Since HCMV IgG increases in individuals with virus shedding [17] and its level positively correlates with HCMV-specific IgM [18], an increase of HCMV IgG during latency might indicate frequent or recent virus reactivation
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