3 Key Takeaways
Plain English Summary- 01Core Finding
Normalized protein expression values were analyzed using linear mixed effects models, partial least squares-discriminant analysis, and gene set enrichment analysis.
- 02Study Evidence
Tested in a observational cohort study at the real-world cohort stage.
- 03Practical Meaning
Observational cohort findings reveal real-world links, though lifestyle or unmeasured factors cannot be fully ruled out without an RCT.
What This Means for You
These data identify a CMV-associated plasma proteomic signature in treated HIV, characterized by immunoinhibitory/cytotoxic programs, supporting targeting CMV to reduce immune dysregulation and related comorbidities in PWH.
The Discovery
Cytomegalovirus (CMV) is highly prevalent and associated with comorbidities in people with HIV-1 (PWH). CMV contributes to systemic inflammation, but comprehensive analyses of the plasma proteome in PWH with or without CMV are lacking. Plasma proteomes from 59 age- and CD4 count-matched PWH on suppressive antiretroviral therapy (ART) with (CMV+) or without (CMV-) CMV were characterized by inflammation- and cardiometabolic-focused proteomics proximity extension assays. Normalized protein expression values were analyzed using linear mixed effects models, partial least squares-discriminant analysis, and gene set enrichment analysis. T cell phenotypes were assessed by flow cytometry. In covariate-unadjusted linear mixed effects models, 118/350 (33.7%) inflammatory and 27/363 (7.4%) cardiometabolic proteins were differentially expressed (FDR-adjusted p<0.05). Proteins most significantly upregulated in CMV+ participants were associated with immune inhibition (e.g., FcRL6, LY9, HLA-DRA), cytotoxic differentiation (e.g., KLRD1, CD70, SLAMF7), and interferon (an immune-signaling protein)-associated chemotaxis (e.g., CXCL9, CXCL10). Several of the most significantly downregulated proteins in CMV+ PWH were associated with apoptosis (e.g., CASP2, TRIM21, TRAF2). Surface FcRL6 expression was significantly elevated on CD57+CD28- CD8 T cells of CMV+ PWH.
How It Works, Simply
This infectious disease research focuses on inflammation · T cells · Immune response. Researchers evaluated it using an observational cohort study at the real-world cohort stage of medical research.
3 Key Takeaways
Clinical Takeaways- 01Core Finding
Normalized protein expression values were analyzed using linear mixed effects models, partial least squares-discriminant analysis, and gene set enrichment analysis.
- 02Study Evidence
Tested in a observational cohort study at the real-world cohort stage.
- 03Practical Meaning
Observational cohort findings reveal real-world links, though lifestyle or unmeasured factors cannot be fully ruled out without an RCT.
Biological Mechanism & Study Design
Study Design & Cohort
Observational cohort study
Observational cohort study · Real-World Cohort
Biological Pathway & Modality
Inflammation · T cells · Immune response
Intervention: Plasma Proteome Signature of Immune Inhibition is Associated with Cytomegalovirus in
Experimental Findings & Endpoints
Cytomegalovirus (CMV) is highly prevalent and associated with comorbidities in people with HIV-1 (PWH).
CMV contributes to systemic inflammation, but comprehensive analyses of the plasma proteome in PWH with or without CMV are lacking. Plasma proteomes from 59 age- and CD4 count-matched PWH on suppressive antiretroviral therapy (ART) with (CMV+) or without (CMV-) CMV were characterized by inflammation- and cardiometabolic-focused proteomics proximity extension assays.
Normalized protein expression values were analyzed using linear mixed effects models, partial least squares-discriminant analysis, and gene set enrichment analysis. T cell phenotypes were assessed by flow cytometry.
In covariate-unadjusted linear mixed effects models, 118/350 (33.7%) inflammatory and 27/363 (7.4%) cardiometabolic proteins were differentially expressed (FDR-adjusted p<0.05). Proteins most significantly upregulated in CMV+ participants were associated with immune inhibition (e.g., FcRL6, LY9, HLA-DRA), cytotoxic differentiation (e.g., KLRD1, CD70, SLAMF7), and interferon-associated chemotaxis (e.g., CXCL9, CXCL10).
Several of the most significantly downregulated proteins in CMV+ PWH were associated with apoptosis (e.g., CASP2, TRIM21, TRAF2). Surface FcRL6 expression was significantly elevated on CD57+CD28- CD8 T cells of CMV+ PWH.
Clinical Translation & Practice Context
These data identify a CMV-associated plasma proteomic signature in treated HIV, characterized by immunoinhibitory/cytotoxic programs, supporting targeting CMV to reduce immune dysregulation and related comorbidities in PWH.
The Bottom Line · Clinical Pearl
“These data identify a CMV-associated plasma proteomic signature in treated HIV, characterized by immunoinhibitory/cytotoxic programs, supporting targeting CMV to reduce immune dysregulation and related comorbidities in PWH.”
Published in The Journal of Infectious Diseases · Current Stage: Real-World Cohort