Plasma MicroRNA Signature Panel Predicts the Immune Response After Antiretroviral Therapy in HIV-Infected Patients
BackgroundApproximately 10–40% of people with human immunodeficiency virus (HIV) infection are unable to obtain successful improvements in immune function after antiretroviral therapy (ART). These patients are at greater risk of developing non-acquired immunodeficiency syndrome (AIDS)-related condit...
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Frontiers Media S.A.
2021
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oai:doaj.org-article:5ad973286ce146879bc4e7b8b19ccf432021-11-30T12:54:03ZPlasma MicroRNA Signature Panel Predicts the Immune Response After Antiretroviral Therapy in HIV-Infected Patients1664-322410.3389/fimmu.2021.753044https://doaj.org/article/5ad973286ce146879bc4e7b8b19ccf432021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.753044/fullhttps://doaj.org/toc/1664-3224BackgroundApproximately 10–40% of people with human immunodeficiency virus (HIV) infection are unable to obtain successful improvements in immune function after antiretroviral therapy (ART). These patients are at greater risk of developing non-acquired immunodeficiency syndrome (AIDS)-related conditions, with the accompanying increased morbidity and mortality. Discovering predictive biomarkers can help to identify patients with a poor immune response earlier and provide new insights into the mechanisms of this condition.MethodsA total of 307 people with HIV were enrolled, including 110 immune non-responders (INRs) and 197 immune responders (IRs). Plasma samples were taken before ART, and quantities of plasma microRNAs (miRNAs) were determined using reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR). Candidate biomarkers were established through four phases: discovery, training, validation, and blinded test. Binary logistic regression was used to analyze the combined predictive capacity of the identified miRNAs. The effect of one miRNA, miR-16-5p, on T cell function was assessed in vitro.ResultsExpression of five miRNAs (miR-580, miR-627, miR-138-5p, miR-16-5p, and miR-323-3p) was upregulated in the plasma of INRs compared with that in IRs. Expression of these miRNAs was negatively correlated with both CD4+ T cell counts and the increase in the proportion of CD4+ T cells after one year of ART. These five miRNAs were combined in a predictive model, which could effectively identify INRs or IRs. Furthermore, we found that miR-16-5p inhibits CD4+ T cell proliferation by regulating calcium flux.ConclusionWe established a five-miRNA panel in plasma that accurately predicts poor immune response after ART, which could inform strategies to reduce the incidence of this phenomenon and improve the clinical management of these patients.Jun-Nan LvJun-Nan LvJia-Qi LiJia-Qi LiYing-Bin CuiYuan-Yuan RenYuan-Yuan RenYa-Jing FuYa-Jing FuYong-Jun JiangYong-Jun JiangHong ShangHong ShangZi-Ning ZhangZi-Ning ZhangFrontiers Media S.A.articleHIVimmunological non-respondersmicroRNAbiomarkerARTImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021) |
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DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
HIV immunological non-responders microRNA biomarker ART Immunologic diseases. Allergy RC581-607 |
| spellingShingle |
HIV immunological non-responders microRNA biomarker ART Immunologic diseases. Allergy RC581-607 Jun-Nan Lv Jun-Nan Lv Jia-Qi Li Jia-Qi Li Ying-Bin Cui Yuan-Yuan Ren Yuan-Yuan Ren Ya-Jing Fu Ya-Jing Fu Yong-Jun Jiang Yong-Jun Jiang Hong Shang Hong Shang Zi-Ning Zhang Zi-Ning Zhang Plasma MicroRNA Signature Panel Predicts the Immune Response After Antiretroviral Therapy in HIV-Infected Patients |
| description |
BackgroundApproximately 10–40% of people with human immunodeficiency virus (HIV) infection are unable to obtain successful improvements in immune function after antiretroviral therapy (ART). These patients are at greater risk of developing non-acquired immunodeficiency syndrome (AIDS)-related conditions, with the accompanying increased morbidity and mortality. Discovering predictive biomarkers can help to identify patients with a poor immune response earlier and provide new insights into the mechanisms of this condition.MethodsA total of 307 people with HIV were enrolled, including 110 immune non-responders (INRs) and 197 immune responders (IRs). Plasma samples were taken before ART, and quantities of plasma microRNAs (miRNAs) were determined using reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR). Candidate biomarkers were established through four phases: discovery, training, validation, and blinded test. Binary logistic regression was used to analyze the combined predictive capacity of the identified miRNAs. The effect of one miRNA, miR-16-5p, on T cell function was assessed in vitro.ResultsExpression of five miRNAs (miR-580, miR-627, miR-138-5p, miR-16-5p, and miR-323-3p) was upregulated in the plasma of INRs compared with that in IRs. Expression of these miRNAs was negatively correlated with both CD4+ T cell counts and the increase in the proportion of CD4+ T cells after one year of ART. These five miRNAs were combined in a predictive model, which could effectively identify INRs or IRs. Furthermore, we found that miR-16-5p inhibits CD4+ T cell proliferation by regulating calcium flux.ConclusionWe established a five-miRNA panel in plasma that accurately predicts poor immune response after ART, which could inform strategies to reduce the incidence of this phenomenon and improve the clinical management of these patients. |
| format |
article |
| author |
Jun-Nan Lv Jun-Nan Lv Jia-Qi Li Jia-Qi Li Ying-Bin Cui Yuan-Yuan Ren Yuan-Yuan Ren Ya-Jing Fu Ya-Jing Fu Yong-Jun Jiang Yong-Jun Jiang Hong Shang Hong Shang Zi-Ning Zhang Zi-Ning Zhang |
| author_facet |
Jun-Nan Lv Jun-Nan Lv Jia-Qi Li Jia-Qi Li Ying-Bin Cui Yuan-Yuan Ren Yuan-Yuan Ren Ya-Jing Fu Ya-Jing Fu Yong-Jun Jiang Yong-Jun Jiang Hong Shang Hong Shang Zi-Ning Zhang Zi-Ning Zhang |
| author_sort |
Jun-Nan Lv |
| title |
Plasma MicroRNA Signature Panel Predicts the Immune Response After Antiretroviral Therapy in HIV-Infected Patients |
| title_short |
Plasma MicroRNA Signature Panel Predicts the Immune Response After Antiretroviral Therapy in HIV-Infected Patients |
| title_full |
Plasma MicroRNA Signature Panel Predicts the Immune Response After Antiretroviral Therapy in HIV-Infected Patients |
| title_fullStr |
Plasma MicroRNA Signature Panel Predicts the Immune Response After Antiretroviral Therapy in HIV-Infected Patients |
| title_full_unstemmed |
Plasma MicroRNA Signature Panel Predicts the Immune Response After Antiretroviral Therapy in HIV-Infected Patients |
| title_sort |
plasma microrna signature panel predicts the immune response after antiretroviral therapy in hiv-infected patients |
| publisher |
Frontiers Media S.A. |
| publishDate |
2021 |
| url |
https://doaj.org/article/5ad973286ce146879bc4e7b8b19ccf43 |
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