Cytomegalovirus Antibody Levels, Inflammation, and Mortality Among Elderly Latinos Over 9 Years of Follow-up

Abstract

This study examined the relation between immune response to cytomegalovirus (CMV) and all-cause and cardiovascular disease (CVD) mortality, and possible mediating mechanisms. Data were derived from the Sacramento Area Latino Study on Aging, a population-based study of older Latinos (aged 60-101 years) in California followed in 1998-2008. CMV immunoglobulin G (IgG), tumor necrosis factor, and interleukin-6 were assayed from baseline blood draws. Data on all-cause and CVD mortality were abstracted from death certificates. Analyses included 1,468 of 1,789 participants. For individuals with CMV IgG antibody titers in the highest quartile compared with lower quartiles, fully adjusted models showed that all-cause mortality was 1.43 times (95% confidence interval: 1.14, 1.79) higher over 9 years. In fully adjusted models, the hazard of CVD mortality was also elevated (hazard ratio = 1.35, 95% confidence interval: 1.01, 1.80). A composite measure of tumor necrosis factor and interleukin-6 mediated a substantial proportion of the association between CMV and all-cause (18.9%, P < 0.001) and CVD (29.0%, P = 0.02) mortality. This study is the first known to show that high CMV IgG antibody levels are significantly related to mortality and that the relation is largely mediated by interleukin-6 and tumor necrosis factor. Further studies investigating methods for reducing IgG antibody response to CMV are warranted.

Cytomegalovirus infection does not impact on survival or time to first treatment in patients with chronic lymphocytic leukemia

“…In addition, high HCMV‐specific antibody titers have been correlated with poor clinical outcome in elderly donors 28 but we were unable to demonstrate this in patients with B‐CLL. The development of hypogammaglobulinemia is a feature of progressive CLL but unlike other herpes viruses such as VZV and EBV, HCMV‐specific IgG titers have been shown to increase with disease progression and progressive hypogammaglobulinemia, Indeed, in a large cohort of patients with CLL, almost 50% demonstrated an increase in their CMV‐specific IgG titer 4.6 years later and all CMV positive patients were still found to have detectable CMV IgG 37.…”

“…This may be due partly to the younger age of the patients with B‐CLL compared with studies of healthy elderly people, which have focused predominantly on those between 70 and 100 years of age 11, 28, 29. In addition, the detrimental impact of chronic HCMV on the health of older people has been linked with elevated levels of inflammatory markers, including IL‐6 23, 30, 31, which are often already increased in patients with B‐CLL and may therefore confound any impact of HCMV on further health outcomes 32, 33.…”

Cytomegalovirus‐Productive Infection Is Associated With Acute Coronary Syndrome

“…Data on the involvement of HHVs in human atherosclerosis are far less conclusive13 and are predominantly based on epidemiological studies. These data do not allow assessment of actual viral infection in patients because antibodies (and cell‐associated DNA) may provide evidence of past infections rather than infections that are active at the time of analysis 14, 15…”

Mouse CMV infection delays antibody class switch upon an unrelated virus challenge

“…CMV infection is associated with increased numbers of CD28-or CD45RA+ T-cells in both CD4 and CD8 subsets (Looney et al, 1999) in a manner that recapitulates the aging-related accumulation of these subsets (Chidrawar et al, 2009). CMV is also associated with functional immune deficits in the aging host, including lower counts of Epstein Barr Virus (EBV) specific CD8 T-cells (Khan et al, 2004), increased reactivation of varicella-zoster virus (Ogunjimi et al, 2013) or excess mortality (Roberts et al, 2010;Wikby et al, 2002), mainly due to vascular causes (Roberts et al, 2010;Savva et al, 2013).…”