T-Cell Activation Independently Associates With Immune Senescence in HIV-Infected Recipients of Long-term Antiretroviral Treatment

Jiménez, Viviana Cobos; Wit, Ferdinand W. N. M.; Joerink, Maaike; Maurer, Irma; Harskamp, Agnes M.; Schouten, Judith; Prins, Jan M.; Leeuwen, Ester M. M. van; Booiman, Thijs; Deeks, Steven G.; Reiss, Peter; Kootstra, Neeltje A.

doi:10.1093/infdis/jiw146

Cited by 97 publications

(82 citation statements)

References 48 publications

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“…Our findings support the concept that excessive immune activation can lead to premature immune senescence with negative effects on B cells [4, 51]. …”

Section: Discussionsupporting

confidence: 89%

Paradoxical aging in HIV: immune senescence of B Cells is most prominent in young age

Rinaldi

Pallikkuth

George

et al. 2017

Aging

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Combination antiretroviral therapies (cART) can lead to normal life expectancy in HIV-infected persons, and people aged >50 yrs represent the fastest growing HIV group. Although HIV and aging are independently associated with impaired humoral immunity, immune status in people aging with HIV is relatively unexplored. In this study influenza vaccination was used to probe age associated perturbations in the B cell compartment of HIV-negative “healthy controls” (HC) and virologically controlled HIV-infected participants on cART (HIV) (n=124), grouped by age as young (<40 yrs), middle-aged (40-59yrs) or old (≥60 yrs). H1N1 antibody response at d21 post-vaccination correlated inversely with age in both HC and HIV. Immunophenotyping of cryopreserved PBMC demonstrated increased frequencies of double negative B cells and decreased plasmablasts in old compared to young HC. Remarkably, young HIV were different from young HC but similar to old HC in B cell phenotype, influenza specific spontaneous (d7) or memory (d21) antibody secreting cells. We conclude that B cell immune senescence is a prominent phenomenon in young HIV in comparison to young HC, but distinctions between old HIV and old HC are less evident though both groups manifest age-associated B cell dysfunction.

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“…Our findings support the concept that excessive immune activation can lead to premature immune senescence with negative effects on B cells [4, 51]. …”

Section: Discussionsupporting

confidence: 89%

Paradoxical aging in HIV: immune senescence of B Cells is most prominent in young age

Rinaldi

Pallikkuth

George

et al. 2017

Aging

View full text Add to dashboard Cite

show abstract

“…Microbial translocation as determined by elevated sCD14 has been linked with increased mortality among HIV-infected individuals [25] and individuals on haemodialysis [27]. Importantly, sCD14 concentrations are also elevated in hepatitis C virus infection [28], tuberculosis [29], inflammatory disorders such as rheumatoid arthritis and systemic lupus erythematosus [30] and in HIV associated accelerated aging [31]. The diversity of conditions in which sCD14 levels are reported elevated perhaps limits the specificity of the biomarker to any of them thereby limiting its utility as a diagnostic or prognostic marker.…”

Section: Discussionmentioning

confidence: 99%

Plasma IP-10 Concentrations Correlate Positively with Viraemia and Inversely with CD4 Counts in Untreated HIV Infection

Mhandire

Mlambo

Zijenah

et al. 2017

TOAIDJ

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Background:Chronic immune activation is a feature of HIV infection associated with accelerated HIV disease progression. There is conflicting data on the association of biomarkers of immune activation with traditional markers of HIV disease progression; CD4 counts and viral load (VL).Objective:The study aimed to determine the association of biomarkers of immune activation; interferon (IFN)-γ-induced protein 10 (IP-10) and soluble cluster of differentiation 14 (sCD14) in chronic HIV infection with traditional markers of HIV disease progression.Methods:We collected demographic data, enumerated CD4 counts and quantified VL in 183 antiretroviral therapy (ART)-naive adults with chronic HIV infection. Plasma concentrations of IP-10 and sCD14 were quantified in the ART-naive adults with chronic HIV infection and 75 HIV-uninfected controls.Results:IP-10 concentrations were significantly higher in the HIV-infected group (median; 257.40pg/ml, IQR; 174.08-376.32) than in the HIV-uninfected (median; 86.19pg/ml, IQR; 67.70-116.39) (P<0.001). Similarly, sCD14 concentrations were significantly higher in the HIV-infected (median; 1.45µg/ml, IQR; 1.02-2.16) group than in the controls (median; 0.89µ/ml, IQR; 0.74-1.18) (P<0.001). High log10 IP-10 concentrations were positively correlated with high log10 viral loads (Spearman’s correlation coefficient [R]=0.21, P=0.003) and inversely correlated with low CD4 counts (R= -0.19, P=0.011). In contrast, log10 sCD14 was not significantly associated with either log10 viral loads (R=0.03, P=0.707) nor CD4 count (R=-0.04, P=0.568).Conclusion:We conclude that plasma sCD14 and IP-10 were elevated in the HIV-infected patients compared to HIV-uninfected individuals possibly due to on-going immune activation. In addition, plasma high concentrations of IP-10 but not sCD14 concentrations are associated with high VL and low CD4 count.

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“…Multiple research groups have corroborated a strong link between chronic inflammation and decrease of TL in cell subsets. For instance, studies on HIV elucidated the link between chronic infection and telomere attrition in CD4 + and CD8 + T cells 23 24. The replicative senescence of T lymphocytes is not limited to HIV since it is broadly investigated in association with malignancies,25 autoimmune disorders26 and environmental mediators 27 28.…”

Section: Discussionmentioning

confidence: 99%

Patients with gout have short telomeres compared with healthy participants: association of telomere length with flare frequency and cardiovascular disease in gout

et al. 2017

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Vazirpanah, N. et al. (2017) Patients with gout have short telomeres compared with healthy participants: association of telomere length with flare frequency and cardiovascular disease in gout. Annals of the Rheumatic Diseases, 76(7), pp. 1309-1315. (doi:10.1136/annrheumdis-2016-210538) This is the author's final accepted version.There may be differences between this version and the published version. You are advised to consult the publisher's version if you wish to cite from it.http://eprints.gla.ac.uk/139064/ Abstract:Aim and background: Chronic inflammation associates with increased senescence, which is a strong predictor for cardiovascular disease. We hypothesised that inflammation accelerates senescence and thereby enhances the risk of cardiovascular disease in gout.Methods: We assessed replicative senescence by quantifying telomere length (TL) in a discovery cohort of 145 Dutch patients with gout and 273 healthy individuals and validated our results in 474 patients with gout and 293 healthy participants from New-Zealand. Subsequently, we investigated the effect of cardiovascular disease on TL of all participants. Also, we measured TL of CD4 + and CD8 + T lymphocytes, B lymphocytes, monocytes, natural killer (NK) cells and plasmacytoid dendritic cells (pDCs). Additionally, we assessed the potential temporal difference in TL and telomerase activity.Results: TL in PBMCs of healthy donors decreased over time reflecting normal ageing. Patients with gout demonstrated shorter telomeres (P=0.001, R 2 =0.01873). In fact, the extent of telomere erosion in patients with gout was higher at any age as compared to healthy counterparts at any age (P<0.0001, R 2 =0.02847). Patients with gout with cardiovascular disease had the shortest telomeres and TL was an independent risk factor for cardiovascular disease in patients with gout (P=0.001). TL was inversely associated with the number of gouty flares (P=0.005).Conclusions: Patients with gout have shorter telomeres than healthy participants, reflecting increased cellular senescence. Telomere shortening was associated with the number of flares, and with cardiovascular disease in people with gout.

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T-Cell Activation Independently Associates With Immune Senescence in HIV-Infected Recipients of Long-term Antiretroviral Treatment

Cited by 97 publications

References 48 publications

Paradoxical aging in HIV: immune senescence of B Cells is most prominent in young age

Paradoxical aging in HIV: immune senescence of B Cells is most prominent in young age

Plasma IP-10 Concentrations Correlate Positively with Viraemia and Inversely with CD4 Counts in Untreated HIV Infection

Patients with gout have short telomeres compared with healthy participants: association of telomere length with flare frequency and cardiovascular disease in gout

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