Is Pulmonary non-Tuberculous Mycobacterial Disease Linked with a High Burden of Latent Cytomegalovirus?

Amran, Fathiah S; Kim, Kyungchul; Lim, Andrew; Thomson, Rachel; Lee, Silvia; Waterer, Grant; Price, Patricia

doi:10.1007/s10875-016-0233-1

Cited by 8 publications

(10 citation statements)

References 20 publications

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“…One study associated CMV antibody levels with TNF‐α and IL‐6 in sera from young and elderly individuals . We found no correlation between CMV antibody levels and sTNFR1 in healthy controls or patients with nontuberculous mycobacteria, and there was no consistent pattern here in RTR or healthy adults. Our data suggest that CMV antibody is not a surrogate marker of ‘inflammaging’ .…”

Section: Discussioncontrasting

confidence: 79%

“…The use of antibodies as a metric of the burden of CMV is complicated by increased levels in older individuals, demonstrated in the Australian population. 21 Here, transplantation overcame the effect of age, but the levels of CMV antibody were elevated in RTR and increased with time posttransplant. This is consistent with episodic subclinical CMV reactivations in patients on antirejection therapy, as evidenced by the detection of CMV DNA in some (not all) RTR.…”

Section: Discussionmentioning

confidence: 93%

“…Evaluations of the effects of CMV require a robust measure of the burden of CMV in an individual which is addressed here in two distinct populations: RTR and healthy adults with a similar age and gender mix. The use of antibodies as a metric of the burden of CMV is complicated by increased levels in older individuals, demonstrated in the Australian population . Here, transplantation overcame the effect of age, but the levels of CMV antibody were elevated in RTR and increased with time post‐transplant.…”

Section: Discussionmentioning

confidence: 95%

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A high burden of cytomegalovirus marks poor vascular health in transplant recipients more clearly than in the general population

et al. 2019

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ObjectivesMeta‐analyses have now confirmed that persistent infections with cytomegalovirus (CMV) can accelerate the onset of diseases of ageing, notably cardiovascular pathologies. We address the circumstances in which the association may be strong enough to warrant intervention to reduce the viral burden.ResultsWe compare markers of the burden of CMV with established indices of vascular pathology in healthy adults (n = 82) and in renal transplant recipients (RTR; n = 81). Levels of all inflammatory and vascular biomarkers and CMV antibodies were higher in RTR, and flow‐mediated dilation (FMD) values were lower indicating inferior endothelial function. In multivariable regression models without adjustment for estimated glomerular filtration rate (eGFR), CMV antibody levels, age and gender were independently associated with FMD in RTR, whilst only CRP associated with FMD in healthy adults. After adjustment for eGFR, associations between CMV antibody and FMD in RTR were reduced.MethodsCarotid intima‐media thickness, FMD, eGFR and plasma levels of CMV antibodies (reactive with a lysate, CMV IE‐1 or CMV gB), ICAM‐1, VCAM‐1, P‐selectin, sIFNαR2, sTNFR1, sCD14 and CRP were determined.ConclusionLevels of CMV antibody predict declining endothelial health in RTR and not in healthy adults, presumably by reflecting a high burden of CMV. The levels of CMV antibodies were a poor reflection of plasma biomarkers thought to reflect ‘inflammaging’ or vascular damage.

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Section: Discussioncontrasting

confidence: 79%

Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 95%

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A high burden of cytomegalovirus marks poor vascular health in transplant recipients more clearly than in the general population

et al. 2019

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“…Accordingly we find no concordance between levels of soluble TNF receptors and CMV antibodies in HIV patients stable on ART [19] or older individuals with or without NTM disease [49]. We conclude that circulating pro-inflammatory markers are a poor metric of the footprint of CMV in these situations.…”

Section: And Inflammagingcontrasting

confidence: 59%

“…CMV has been linked with several diseases of aging. In addition to cardiovascular disease (CVD), we demonstrated higher titres of antibodies reactive with CMV in patients with chronic obstructive pulmonary disease or pulmonary non-tuberculous mycobacterial (NTM) infections [48,49]. However T-cell and antibody responses to CMV rise with age [19,50], so immune activation associated with age and other infections must be considered.…”

Section: The Clinical Footprint Of CMVmentioning

confidence: 99%

HIV patients, healthy aging and transplant recipients can reveal the hidden footprints of CMV

Waters

Brook

Lee

et al. 2018

Clinical Immunology

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Cytomegalovirus (CMV) is a β-herpesvirus. Latent infections are common in all populations. However age-associated increases in levels of CMV-reactive antibody are testament to repeated reactivations and periods of viral replication. CMV has been associated with several diseases of aging, including vasculopathy and neurocognitive impairment. These conditions occur at a younger age in persons with particularly high burdens of CMV - transplant recipients and people living with HIV. Here we define the "clinical footprints" as immunopathologies triggered by CMV that develop over many years. A high burden of CMV also drives accumulation of multifunctional terminally-differentiated αβ T-cells, a novel population of Vδ2 γδ T-cells, and a population of CD56 NK cells lacking a key regulatory molecule. An understanding of these "immunological footprints" of CMV may reveal how they collectively promote the "clinical footprints" of the virus. This is explored here in transplant recipients, HIV patients and healthy aging.

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A systematic review of the impact of psychosocial factors on immunity: Implications for enhancing BCG response against tuberculosis

Hayward

Dowd

Fletcher

et al. 2020

SSM - Population Health

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BackgroundTuberculosis (TB) remains an urgent global public health priority, causing 1.5 million deaths worldwide in 2018. There is evidence that psychosocial factors modulate immune function; however, how this may influence TB risk or BCG vaccine response, and whether this pathway can be modified through social protection, has not been investigated. This paper aims to: a) systematically review evidence of how psychosocial factors influence the expression of biomarkers of immunity, and b) apply this general evidence to propose plausible TB-specific pathways for future study.MethodsPapers reporting on the impact of psychosocial stressors on immune biomarkers in relation to infectious disease risk were identified through a search of the databases MEDLINE, PsycINFO, Global Health and PsycEXTRA alongside reference list and citation searching of key papers. Data extraction and critical appraisal were carried out using a standardised form. The findings were tabulated and synthesised narratively by infectious disease category, and used to propose plausible mechanisms for how psychosocial exposures might influence immune outcomes relevant to TB and BCG response.Results27,026 citations were identified, of which 51 met the inclusion criteria. The literature provides evidence of a relationship between psychosocial factors and immune biomarkers. While the direction and strength of associations is heterogenous, some overarching patterns emerged: adverse psychosocial factors (e.g. stress) were generally associated with compromised vaccine response and higher antibody titres to herpesviruses, and vice versa for positive psychosocial factors (e.g. social support).ConclusionsThe evidence identifies pathways linking psychosocial factors and immune response: co-viral infection and immune suppression, both of which are potentially relevant to TB and BCG response. However, the heterogeneity in the strength and nature of the impact of psychosocial factors on immune function, and lack of research on the implications of this relationship for TB, underscore the need for TB-specific research.

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Is Pulmonary non-Tuberculous Mycobacterial Disease Linked with a High Burden of Latent Cytomegalovirus?

Cited by 8 publications

References 20 publications

A high burden of cytomegalovirus marks poor vascular health in transplant recipients more clearly than in the general population

A high burden of cytomegalovirus marks poor vascular health in transplant recipients more clearly than in the general population

HIV patients, healthy aging and transplant recipients can reveal the hidden footprints of CMV

A systematic review of the impact of psychosocial factors on immunity: Implications for enhancing BCG response against tuberculosis

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