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Profiling of proteome changes in plasma of HIV-infected patients receiving antiretroviral therapy

ABSTRACT: Antiretroviral therapy (ART) prevents HIV-1 onward transmission and disease progression, leading to excellent prognosis people living with HIV-1 (PWH). However, significant side effects, complications and impaired immune reconstitution still persist along with ART. We aimed to profile proteome changes in plasma before and after ART to identify the molecular pathways altered by ART and finding potential targets to improve the health of PWH.

ORGANISM(S): Homo Sapiens

SUBMITTER: Haiteng Deng

PROVIDER: PXD045070 | iProX | Tue Mar 08 00:00:00 GMT 2022

REPOSITORIES: iProX

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Profiling of proteome changes in plasma of HIV-infected patients receiving antiretroviral therapy.

Li Ting T Qu Hong H Ding Haibo H Deng Haiteng H Chen Yuling Y

Proteomics. Clinical applications 20221010 6

<h4>Purpose</h4>Antiretroviral therapy (ART) prevents human immunodeficiency virus (HIV)-1 onward transmission and disease progression, leading to excellent prognosis in people living with HIV-1 (PWH). However, side effects, complications, and impaired immune reconstitution persist in some patients treated with ART. We aimed to profile proteome changes in plasma before and after ART to identify the molecular pathways altered by ART.<h4>Experimental design</h4>Quantitative proteomics analysis bas ...[more]

PMID: 35920599

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Project description:Background. HIV-infected individuals on antiretroviral therapy (HIV/ART) experience higher levels of non-AIDS morbidity than uninfected people, which is believed to be driven by inflammation that persists despite viral suppression. Elevations in plasma cytokines, coagulation markers and both innate and adaptive immune cell activation during untreated infection are often incompletely reversed by ART and associated with these morbidities. Monocytes/macrophages play a central role in many of these complications including neurocognitive and cardiovascular disease. Results. We investigated monocyte surface markers, gene expression and plasma cytokines in 11 HIV-infected older individuals (median age 53 years) who started therapy with low CD4 counts (median 129 cells/ul), with elevated hsCRP (≥2mg/L) despite long-term ART (median 7.4 years), along with age, gender, race and smoking status-matched controls. Major monocyte subsets (based on CD14/CD16/CD163) were not different from controls, but surface levels differed for CD163 (p=0.022), PD1 (p=0.015) and a trend for tissue factor (p=0.098). As a group, HIV/ART subjects had elevated levels of plasma CCL2 (MCP-1; p=0.0001), CXCL9 (MIG; p=0.04) and sIL2R (p=0.015), which were highly correlated, whereas sCD14 and several other markers were not significantly elevated. However, principal component analysis of soluble markers revealed that about half of HIV/ART subjects clustered with controls, whereas the remainder were distinct, driven by IL-10, CCL11, CXCL10, CXCL11 as well as CCL2, CXCL9 and sIL2R. Outlier subjects were significantly older than those who clustered with controls. Gene expression analysis unexpectedly revealed downregulation in HIV/ART monocytes of multiple genes linked to immune functions including inflammation, immune cell development and cell-cell signaling. Conclusions. These results reveal a novel pattern of immune dysregulation involving both aberrant inflammation and monocyte dysfunction, which suggests complex mechanisms linking monocytes and HIV/ART comorbidities.

Dataset Information

Profiling of proteome changes in plasma of HIV-infected patients receiving antiretroviral therapy

Publications

Profiling of proteome changes in plasma of HIV-infected patients receiving antiretroviral therapy.

Similar Datasets

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