Insulin resistance is linked to a specific profile of immune activation in human subjects

Cezar, Renaud; Desigaud, Delphine; Pastore, Manuela; Kundura, Lucy; Dupuy, Anne‐Marie; Cognot, Chantal; Vincent, Thierry; Reynès, Christelle; Sabatier, Robert; Maggia, Elisabeth; Corbeau, Pierre

doi:10.1038/s41598-021-91758-3

Cited by 2 publications

(3 citation statements)

References 44 publications

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“…Our work unveils an immune activation signature linked to HIV-associated pre-frailty. It would now be of interest to perform the same kind of study in a non-specific population to test whether a similar signature is generally present in frailty, as we have shown that this is the case with insulin resistance [ 30 , 45 ]. In addition to its pathophysiological interest, the present study may have an implication for the management of frailty.…”

Section: Discussionmentioning

confidence: 99%

“…We then generated a heatmap using the classification of patients and markers. For the supervised analysis, a linear discriminant analysis was applied to each solution (immunological marker combinations) using the R package MASS [ 30 ]. This supervised method creates linear combinations of all variables in order to optimize the separation of known classes.…”

Section: Methodsmentioning

confidence: 99%

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Immune profiles of pre-frail people living with HIV-1: a prospective longitudinal study

Kundura,

Cezar,

Gimenez

et al. 2024

Immun Ageing

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Background People living with HIV (PLWH) are at risk of frailty, which is predictive for death. As an overactivity of the immune system is thought to fuel frailty, we characterized the immune activation profiles linked to frailty. Methods We quantified twenty-seven activation markers in forty-six virological responders (four females and forty-two males; median age, 74 years; median duration of infection, 24 years; median duration of undetectability, 13 years), whose frailty was determined according to the Fried criteria. T cell and NK cell activation was evaluated by flow cytometry, using a panel of cell surface markers. Soluble markers of inflammation, and monocyte activation and endothelial activation were measured by ELISA. The participants’ immune activation was profiled by an unsupervised double hierarchical clustering analysis. We used ANOVA p-values to rank immunomarkers most related to Fried score. A Linear Discriminant Analysis (LDA) was performed to link immune activation markers to frailty. Results 41% of the participants were pre-frail, including 24% with a Fried score of 1, and 17% with a Fried score of 2. ANOVA identified the 14 markers of T cell, monocyte, NK cell, endothelial activation, and inflammation the most linked to Fried 3 classes. The LDA performed with these 14 markers was capable of discriminating volunteers according to their Fried score. Two out of the 5 immune activation profiles revealed by the hierarchical clustering were linked to and predictive of pre-frailty. These two profiles were characterized by a low percentage of CD4 T cells and a high percentage of CD8 T cells, activated CD4 T cells, CD8 T cells, and NK cells, and inflammation. Conclusions We identified a particular immune activation profile associated with pre-frailty in PLWH. Profiling participants at risk of developing frailty might help to tailor the screening and prevention of medical complications fueled by loss of robustness. Further studies will indicate whether this frailty signature is specific or not of HIV infection, and whether it also precedes frailty in the general population.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Immune profiles of pre-frail people living with HIV-1: a prospective longitudinal study

Kundura,

Cezar,

Gimenez

et al. 2024

Immun Ageing

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“…As previously described (36,(39)(40)(41)(42), we then performed a double hierarchical clustering analysis again, using the following activation markers: sCD163, sTNFRI, tPA, sEPCR, the percentage of activated (CD38+, CD38hi, and/or HLA-DR+), exhausted (PD-1+), senescent (CD57+, eventually CD27-and eventually CD28-), naïve (CD45RA+CD27+), central (CD45RA-CD27+) and effector (CD45RA-CD27-) memory CD4+ and CD8+ T cells, as well as activated (HLA-DR+), dysfunctional (CD56-), and senescent (CD57+) NK cells. Percentages were preferred to absolute numbers as these are more stable over time.…”

Section: Identification Of Immune Activation Profiles Presented By 24...mentioning

confidence: 99%

Low levels of peripheral blood activated and senescent T cells characterize people with HIV-1-associated neurocognitive disorders

Kundura,

Cezar,

Pastore

et al. 2023

Front. Immunol.

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BackgroundHIV infection induces a 75% increase in the risk of developing neurocognitive impairment (NCI), which has been linked to immune activation. We therefore looked for immune activation markers correlating with NCI.MethodSixty-five people aged 55-70 years living with controlled HIV-1 infection were enrolled in the study and their neurocognitive ability was assessed according to the Frascati criteria. Fifty-nine markers of T4 cell, T8 cell, NK cell, and monocyte activation, inflammation and endothelial activation were measured in their peripheral blood. White matter hyperintensities (WMH) were identified by magnetic resonance imaging. Double hierarchical clustering was performed for the activation markers and 240 patients including the 65 whose neurocognitive performance had been evaluated.ResultsThirty-eight percent of volunteers presented NCI. Twenty-four percent of them were asymptomatic and fourteen percent had a mild disorder. Strikingly, activated (HLA-DR+) as well as senescent (CD57+CD28-CD27±) T4 cells and T8 cells were less prevalent in the peripheral blood of participants with NCI than in participants without the disorder. Accordingly, the percentage of HLA-DR+ T4 cells was lower in volunteers with periventricular and deep WMH. The double hierarchical clustering unveiled six different immune activation profiles. The neurocognitive performances of participants with two of these six profiles were poor. Here again, these two profiles were characterized by a low level of T4 and T8 cell activation and senescence.ConclusionOur observation of low circulating levels of activated and senescent T cells in HIV-1 patients with NCI raises the interesting hypothesis that these lymphocytes may be recruited into the central nervous system.

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Insulin resistance is linked to a specific profile of immune activation in human subjects

Cited by 2 publications

References 44 publications

Immune profiles of pre-frail people living with HIV-1: a prospective longitudinal study

Immune profiles of pre-frail people living with HIV-1: a prospective longitudinal study

Low levels of peripheral blood activated and senescent T cells characterize people with HIV-1-associated neurocognitive disorders

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