Persistent Infection, Inflammation, and Functional Impairment in Older Latinos

Aiello, Allison E.; Haan, Mary N.; Campbell, Christine; Simanek, Amanda M.; Liang, Jersey

doi:10.1093/gerona/63.6.610

Cited by 79 publications

(67 citation statements)

References 38 publications

(74 reference statements)

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“…In particular, we report for the first time an inverse correlation between the intensity of humoral (anti-HCMV IgG) and cellular (anti-HCMV functional proinflammatory T cells) anti-HCMV immune response and basic parameters of cognitive (MMSE) and functional status (ADL) in the elderly. In particular, humoral and CD4 + T cell-specific responses were not associated simply with aging and diseases; they were also associated with cognitive and functional impairment, confirming the evidence that HCMV infection may have an important role in these impairments (39,47). Despite the limitations inherent to cross-sectional protocols, this study reinforces the consistency of the previously recognized association between HCMV seropositivity and frailty by adding a degree of specificity through comparison with anti-EBV response, by adding dose-response relationships through evaluation of the intensity of immune responses, and by adding biological plausibility to the pathogenic mechanisms driven by HCMV infection in diseased compared with healthy elderly.…”

Section: Discussionmentioning

confidence: 62%

Intense Antiextracellular Adaptive Immune Response to Human Cytomegalovirus in Very Old Subjects with Impaired Health and Cognitive and Functional Status

Vescovini¹,

Biasini²,

Telera³

et al. 2010

The Journal of Immunology

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Human aging is characterized by expanded and altered adaptive immune responses to human CMV (HCMV). It is unclear whether this expansion has its origins in age-related homeostatic disturbances or viral reactivation, whether anti-CMV immune surveillance may still be effective, and what are the consequences of this expanded immune response for health and longevity. We conducted an observational cross-sectional study in groups of HCMV-seropositive subjects aged ≥65 y of variable health status to compare the intensity of Ab responses against HCMV with those against EBV and with CD4+ and CD8+ T cell proinflammatory effector responses directed to HCMV-derived pp65 and immediate-early protein 1 synthetic peptides. Ab responses to HCMV, but not to EBV, and anti-HCMV CD4+, but not CD8+, T cell responses were more intense in elderly subjects aged ≥85 y in poor health and were inversely correlated with markers of functional activity and cognitive function. Therefore, humoral and CD4+ T cell anti-HCMV responses were specifically intensified in advanced aging associated with comorbidity and cognitive and functional impairments. Such a distinctive pattern of adaptive immunity indicates that immune responses targeting the extracellular phase of HCMV are increased in these elderly subjects and could represent an indirect effect of localized and undetectable HCMV reactivation. This study demonstrates that the oldest subjects in poor health with physical and mental impairment express intense functional immune responses to extracellular HCMV and suggests that they may be at risk for direct pathogenic effects by HCMV reactivation as well as indirect pathogenic effects linked to proinflammatory anti-HCMV effector responses.

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Section: Discussionmentioning

confidence: 62%

Intense Antiextracellular Adaptive Immune Response to Human Cytomegalovirus in Very Old Subjects with Impaired Health and Cognitive and Functional Status

Vescovini¹,

Biasini²,

Telera³

et al. 2010

The Journal of Immunology

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“…C ytomegalovirus (CMV) infection is ubiquitous among adults with seroprevalence of up to 95% in HIVuninfected elderly populations, 1,2 and as high as 99% in HIV-infected populations. 3 After primary infection, CMV typically establishes latency, but periodically reactivates, particularly in the presence of host immune suppression.…”

Section: Introductionmentioning

confidence: 99%

Physical Function Impairment of Older, HIV-Infected Adults Is Associated with Cytomegalovirus Immunoglobulin Response

Erlandson

Allshouse

Rapaport

et al. 2015

AIDS Research and Human Retroviruses

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Cytomegalovirus (CMV) is associated with poor outcomes, including physical function impairment, in older HIV-uninfected adults. Whether CMV is associated with physical functional impairment in HIV-infected adults is unknown. The primary objective of this study was to determine the relationship between CMV-specific humoral and cell-mediated immune responses with functional impairment in well-controlled HIV infection. In a case-control study, low-function cases were matched by age, gender, and time from HIV diagnosis to highfunction controls. Quantitative CMV IgG and %CMV-specific CD8 + and CD4 + T cells (interferon-c expression following CMV pp65 stimulation) were used to estimate physical function. Among 30 low-function cases and 48 high-function matched controls, CMV IgG ranged from <10 to 8,830 EU/ml, including four controls with results <10 EU/ml. Each log 10 increase in CMV IgG was associated with 5-fold greater odds of low function ( p = 0.01); these findings were robust to adjustment for concomitant CD4 + count, tobacco use, and age; to exclusion of subjects with CMV IgG <10 EU/ml; and to adjustment for hepatitis C viremia. %CMV-specific CD4 + or CD8 + T cells were not associated with low function. In bivariable models, the relationship between CMV IgG and physical function was attenuated and was no longer significant when including IL-6, CD4/CD8 ratio, or the Veterans Aging Cohort Study Index score. High levels of CMV-specific IgG were associated with impaired physical function. Attenuation of the strength of this association in bivariable models suggests an indirect relationship mediated by systemic inflammation and immune suppression.

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“…CMV has been linked with well-known clinical disorders including cancer, 7 cardiovascular disease 8,9 and functional impairment in the elderly. 10 CMV has been proposed as a driving force in immunosenescence. 11,12 In infected individuals, CMV interferes with the normal functioning of the immune system in many ways.…”

Section: Introductionmentioning

confidence: 99%

Genome-wide association study does not reveal major genetic determinants for anti-cytomegalovirus antibody response

et al. 2011

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Cytomegalovirus (CMV) causes an infection, which is followed by a lifelong latency. CMV has received much attention in clinical studies, but little is known about the genetic basis of this common infection. To identify genetic polymorphisms associated with the susceptibility to and strength of anti-CMV immunoglobulin G (IgG) response to CMV infection, we conducted a genome-wide association study (GWAS) using an Illumina BeadChip containing 670 000 probes and participants from the Cardiovascular Risk in Young Finns Study, including 1486 anti-CMV IgG seropositive and 648 seronegative individuals. Statistical analyses were performed using logistic (for susceptibility) and linear regression (for strength of antibody response). None of single-nucleotide polymorphisms (SNPs) was found to be associated with susceptibility to CMV infection at the level of genome-wide significance (Po5 Â 10 À8). Also, none of the association signals identified reached genome-wide levels of statistical significance in the study of the strength of the antibody response to CMV although five SNPs in AGBL1 gene region displayed a suggestive association (lowest P-value ¼ 1.86 Â 10 À6 ). The results indicate that there is no strong evidence of major host genetic factors involved in either susceptibility to or the strength of antibody response to human CMV infection.

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Persistent Infection, Inflammation, and Functional Impairment in Older Latinos

Cited by 79 publications

References 38 publications

Intense Antiextracellular Adaptive Immune Response to Human Cytomegalovirus in Very Old Subjects with Impaired Health and Cognitive and Functional Status

Intense Antiextracellular Adaptive Immune Response to Human Cytomegalovirus in Very Old Subjects with Impaired Health and Cognitive and Functional Status

Physical Function Impairment of Older, HIV-Infected Adults Is Associated with Cytomegalovirus Immunoglobulin Response

Genome-wide association study does not reveal major genetic determinants for anti-cytomegalovirus antibody response

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