Glutaminolysis and lipoproteins are key factors in late immune recovery in successfully treated HIV-infected patients

Rosado‐Sánchez, Isaac; Rodríguez-Gallego, Esther; Peraire, Joaquim; Viladés, Consuelo; Herrero, Pol; Fanjul, Francisco; Gutiérrez, Félix; Bernal, Enrique; Pelazas, Ricardo; Leal, Manuel; Veloso, Sergi; López‐Dupla, Miguel; Blanco, Julià; Vidal, Francesc; Pacheco, Yolanda M.; Rull, Anna

doi:10.1042/cs20190111

Cited by 22 publications

(28 citation statements)

References 50 publications

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“…Consistent with our data, rs1494558 -A was related to new-onset diabetes development after transplantation, playing an important role in the homeostasis of Treg cells, the regulatory T cells that play a major role in controlling immune responses to self-antigens 33 . Notice that diabetes is a metabolic complication associated with increased cardiovascular disease risk, a non-AIDS-defining clinical event, and INRs are associated with worse long-term clinical prognosis, including a higher risk of progression toward non-AIDS-defining clinical events 34 . Later, the rs1494558 -A and rs1494555 -C genotypes were also associated with an increased risk of acute and chronic graft versus host disease after allogeneic hematopoietic cell transplantation 35 .…”

Section: Discussionmentioning

confidence: 99%

IL-7/IL-7R gene variants impact circulating IL-7/IL-7R homeostasis and ART-associated immune recovery status

Ceausu

Rodríguez-Gallego

Peraire

et al. 2019

Sci Rep

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A relationship between polymorphisms in genes encoding interleukin 7 (IL-7) and its cellular receptor (IL-7R) and antiretroviral therapy (ART)-associated immune recovery in HIV subjects has been previously reported. However, details of this relationship remain unclear, and the association of these polymorphisms with circulating IL-7/IL-7R levels is scarce. Here, we explored whether IL-7/IL-7R axis was associated with quantitative CD4+ T-cell recovery in HIV-infected subjects. IL-7/IL-7R polymorphisms were assessed by genotyping, and multiple inheritance models were used to estimate both, their association with low pre-ART CD4+ T-cell counts and incomplete immune recovery status after 48 weeks of suppressive ART. Integrated data from genetic variants association and soluble plasma IL-7/IL-7R quantification suggest that IL-7/IL-7R genotype expression could alter the homeostatic balance between soluble and membrane-bound receptors. The haplotype analyses indicates that allele combinations impacts pre-ART circulating CD4+ T-cell counts, immune recovery status and the absolute increment of CD4+ T-cell counts. The knowledge about how IL-7/IL-7R axis is related to quantitative CD4+ T-cell recovery and immune recovery status after initiating ART could be useful regarding T-cell reservoirs investigations in HIV subjects.

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Section: Discussionmentioning

confidence: 99%

IL-7/IL-7R gene variants impact circulating IL-7/IL-7R homeostasis and ART-associated immune recovery status

Ceausu

Rodríguez-Gallego

Peraire

et al. 2019

Sci Rep

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“…Total CD4 + T-cell count > 250 cells/µl at 2-3 years after ART initiation, with an undetectable plasma VL. 23,170,180,245 Increase in the CD4 + T-cell count < 50 cells/µl from baseline at 1 year after ART initiation, with plasma HIV RNA < 40 copies/ml.…”

Section: Definition Of "Immunological Nonresponder" Definition Of "Immentioning

confidence: 99%

Incomplete immune reconstitution in HIV/AIDS patients on antiretroviral therapy: Challenges of immunological non-responders

Yang

Zhang

et al. 2020

Journal of Leukocyte Biology

193

214

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The morbidity and mortality of HIV type‐1 (HIV‐1)‐related diseases were dramatically diminished by the grounds of the introduction of potent antiretroviral therapy, which induces persistent suppression of HIV‐1 replication and gradual recovery of CD4+ T‐cell counts. However, ∼10–40% of HIV‐1‐infected individuals fail to achieve normalization of CD4+ T‐cell counts despite persistent virological suppression. These patients are referred to as “inadequate immunological responders,” “immunodiscordant responders,” or “immunological non‐responders (INRs)” who show severe immunological dysfunction. Indeed, INRs are at an increased risk of clinical progression to AIDS and non‐AIDS events and present higher rates of mortality than HIV‐1‐infected individuals with adequate immune reconstitution. To date, the underlying mechanism of incomplete immune reconstitution in HIV‐1‐infected patients has not been fully elucidated. In light of this limitation, it is of substantial practical significance to deeply understand the mechanism of immune reconstitution and design effective individualized treatment strategies. Therefore, in this review, we aim to highlight the mechanism and risk factors of incomplete immune reconstitution and strategies to intervene.

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“…A more recent study from the Netherlands using targeted metabolites of biogenic amine, lipids, oxylipins, and oxidative stress showed minimal change after one year of ART [10]. Another untargeted metabolomics study from Spain indicated that glutaminolysis and lipoproteins are vital factors in slow immune recovery at 96 weeks of antiretroviral therapy [13]. Thus, PLHIV on suppressive ART have an increased risk of metabolomic disorders that can increase their risk of age-related diseases.…”

Section: Introductionmentioning

confidence: 99%

Plasma Metabolic Signature and Abnormalities in HIV-Infected Individuals on Long-Term Successful Antiretroviral Therapy

et al. 2019

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Targeted metabolomics studies reported metabolic abnormalities in both treated and untreated people living with human immunodeficiency virus (HIV) (PLHIV). The present study aimed to understand the plasma metabolomic changes and predicted the risk of accelerated aging in PLHIV on long-term suppressive antiretroviral therapy (ART) in a case-control study setting and its association with the plasma proteomics biomarkers of inflammation and neurological defects. Plasma samples were obtained from PLHIV on successful long-term ART for more than five years (n = 22) and matched HIV-negative healthy individuals (n = 22, HC herein). Untargeted metabolite profiling was carried out using ultra-high-performance liquid chromatography/mass spectrometry/mass spectrometry (UHPLC/MS/MS). Plasma proteomics profiling was performed using proximity extension assay targeting 184 plasma proteins. A total of 250 metabolites differed significantly (p < 0.05, q < 0.1) between PLHIV and HC. Plasma levels of several essential amino acids except for histidine, branched-chain amino acids, and aromatic amino acids (phenylalanine, tyrosine, tryptophan) were significantly lower in PLHIV compared to HC. Machine-learning prediction of metabolite changes indicated a higher risk of inflammatory and neurological diseases in PLHIV. Metabolic abnormalities were observed in amino-acid levels, energetics, and phospholipids and complex lipids, which may reflect known differences in lipoprotein levels in PLHIV that can resemble metabolic syndrome (MetS).

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Glutaminolysis and lipoproteins are key factors in late immune recovery in successfully treated HIV-infected patients

Cited by 22 publications

References 50 publications

IL-7/IL-7R gene variants impact circulating IL-7/IL-7R homeostasis and ART-associated immune recovery status

IL-7/IL-7R gene variants impact circulating IL-7/IL-7R homeostasis and ART-associated immune recovery status

Incomplete immune reconstitution in HIV/AIDS patients on antiretroviral therapy: Challenges of immunological non-responders

Plasma Metabolic Signature and Abnormalities in HIV-Infected Individuals on Long-Term Successful Antiretroviral Therapy

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