Alterations in circulating markers in HIV/AIDS patients with poor immune reconstitution: Novel insights from microbial translocation and innate immunity

Xiao, Qing; Yu, Fang; Yan, Liting; Zhao, Hongxin; Zhang, Fujie

doi:10.3389/fimmu.2022.1026070

Cited by 9 publications

(6 citation statements)

References 145 publications

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“…Among all participants, the number of INRs was 826, accounting for 21.8%, including 21.8% and 22.0% in the training and validation sets, respectively. These outcomes corroborated a previous study that found a percentage of INRs in PLWH of 15–30% [ 31 ]. For early diagnosis and treatment, in this study, we developed and validated a feasible and simple visual nomogram as a new approach for predicting the development of immune recovery.…”

Section: Discussionsupporting

confidence: 92%

Incomplete immune reconstitution and its predictors in people living with HIV in Wuhan, China

Zhang,

Yan,

Luo

et al. 2023

BMC Public Health

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Objective This study aimed to build and validate a nomogram model to predict the risk of incomplete immune reconstitution in people living with HIV (PLWH). Methods Totally 3783 individuals with a confirmed diagnosis of HIV/AIDS were included. A predictive model was developed based on a retrospective set (N = 2678) and was validated using the remaining cases (N = 1105). Univariate and multivariate logistic regression analyses were performed to determine valuable predictors among the collected clinical and laboratory variables. The predictive model is presented in the form of a nomogram, which is internally and externally validated with two independent datasets. The discrimination of nomograms was assessed by calculating the area under the curve (AUC). Besides, calibration curve and decision curve (DCA) analyses were performed in the training and validation sets. Results The final model comprised 5 predictors, including baseline CD4, age at ART initiation, BMI, HZ and TBIL. The AUC of the nomogram model was 0.902, 0.926, 0.851 in the training cohort, internal validation and external cohorts. The calibration accuracy and diagnostic performance were satisfactory in both the training and validation sets. Conclusions This predictive model based on a retrospective study was externally validated using 5 readily available clinical indicators. It showed high performance in predicting the risk of incomplete immune reconstitution in people living with HIV.

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Section: Discussionsupporting

confidence: 92%

Incomplete immune reconstitution and its predictors in people living with HIV in Wuhan, China

Zhang,

Yan,

Luo

et al. 2023

BMC Public Health

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“…The occurrence of INR in HIV/AIDS patients may be affected by multiple factors, mainly including decreased bone marrow hematopoiesis, insufficient thymus output, residual virus replication, co-infection during ART, intestinal flora translocation, abnormal immune activation, type of antiretroviral regimen, baseline CD4 + T cell levels, age, sex, and genetic characteristics ( 4 , 9 ). However, the precise mechanisms underlying INR remain an extremely challenging issue.…”

Section: Introductionmentioning

confidence: 99%

Cellular and molecular insights into incomplete immune recovery in HIV/AIDS patients

Yan

Xiao

et al. 2023

Front. Immunol.

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Highly active antiretroviral therapy (ART) can effectively inhibit virus replication and restore immune function in most people living with human immunodeficiency virus (HIV). However, an important proportion of patients fail to achieve a satisfactory increase in CD4+ T cell counts. This state is called incomplete immune reconstitution or immunological nonresponse (INR). Patients with INR have an increased risk of clinical progression and higher rates of mortality. Despite widespread attention to INR, the precise mechanisms remain unclear. In this review, we will discuss the alterations in the quantity and quality of CD4+ T as well as multiple immunocytes, changes in soluble molecules and cytokines, and their relationship with INR, aimed to provide cellular and molecular insights into incomplete immune reconstitution.

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“…However, despite the complete suppression of HIV replication with ART, 15-30% of patients fail to recover their CD4 + T-cell counts and do not achieve optimal recovery. [1][2][3] These individuals are referred to as immunological non-responders (INRs). [4] After 4-7 years of combined ART (cART), patients with CD4 + T-cell counts below 350-500 cells/mL are classified as INRs, while those with counts above 500 cells/mL are defined as immunological responders (IRs).…”

Section: Introductionmentioning

confidence: 99%

An atlas of immune cell transcriptomes in human immunodeficiency virus-infected immunological non-responders identified marker genes that control viral replication

Chen,

Li,

Liu

et al. 2023

Chinese Medical Journal

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Background: Previous studies have examined the bulk transcriptome of peripheral blood immune cells in acquired immunodeficiency syndrome patients experiencing immunological non-responsiveness. Methods: A single-cell transcriptome sequencing of peripheral blood mononuclear cells obtained from both immunological responders (IRs) (CD4+ T-cell count >500) and immunological non-responders (INRs) (CD4+ T-cell count <300) was conducted. The transcriptomic profiles were used to identify distinct cell subpopulations, marker genes, and differentially expressed genes aiming to uncover potential genetic factors associated with immunological non-responsiveness. Results: Among the cellular subpopulations analyzed, the ratios of monocytes, CD16+ monocytes, and exhausted B cells demonstrated the most substantial differences between INRs and IRs, with fold changes of 39.79, 11.08, and 2.71, respectively. In contrast, the CD4+ T cell ratio was significantly decreased (0.39-fold change) in INRs compared with that in IRs. Similarly, the ratios of natural killer cells and terminal effector CD8+ T cells were also lower (0.37-fold and 0.27-fold, respectively) in the INRs group. In addition to several well-characterized immune cell-specific markers, we identified a set of 181 marker genes that were enriched in biological pathways associated with human immunodeficiency virus (HIV) replication. Notably, ISG15, IFITM3, PLSCR1, HLA-DQB1, CCL3L1, and DDX5, which have been demonstrated to influence HIV replication through their interaction with viral proteins, emerged as significant monocyte marker genes. Furthermore, the differentially expressed genes in natural killer cells were also enriched in biological pathways associated with HIV replication. Conclusions: We generated an atlas of immune cell transcriptomes in HIV-infected IRs and INRs. Host genes associated with HIV replication were identified as markers of, and were found to be differentially expressed in, different types of immune cells.

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Alterations in circulating markers in HIV/AIDS patients with poor immune reconstitution: Novel insights from microbial translocation and innate immunity

Cited by 9 publications

References 145 publications

Incomplete immune reconstitution and its predictors in people living with HIV in Wuhan, China

Incomplete immune reconstitution and its predictors in people living with HIV in Wuhan, China

Cellular and molecular insights into incomplete immune recovery in HIV/AIDS patients

An atlas of immune cell transcriptomes in human immunodeficiency virus-infected immunological non-responders identified marker genes that control viral replication

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