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Interferon-signaling pathways are upregulated in people with HIV with abnormal pulmonary diffusing capacity (DL CO ).
Zhang, Michelle; Dai, Guorui; Smith, Dana L; Zacco, Emanuela; Shimoda, Michiko; Kumar, Nitasha; Girling, Valerie; Gardner, Kendall; Hunt, Peter W; Huang, Laurence; Lin, Jue.
Afiliación
  • Zhang M; Division of HIV, Infectious Diseases, and Global Medicine, Department of Medicine.
  • Dai G; Department of Biochemistry and Biophysics.
  • Smith DL; Department of Biochemistry and Biophysics.
  • Zacco E; Laboratory for Cell Analysis, Helen Diller Comprehensive Cancer Center.
  • Shimoda M; Core Immunology Lab, Division of Experimental Medicine.
  • Kumar N; Core Immunology Lab, Division of Experimental Medicine.
  • Girling V; Core Immunology Lab, Division of Experimental Medicine.
  • Gardner K; Division of HIV, Infectious Diseases, and Global Medicine, Department of Medicine.
  • Hunt PW; Division of Experimental Medicine.
  • Huang L; Division of HIV, Infectious Diseases, and Global Medicine, Department of Medicine.
  • Lin J; Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California, San Francisco, CA, USA.
AIDS ; 38(10): 1523-1532, 2024 Aug 01.
Article en En | MEDLINE | ID: mdl-38819840
ABSTRACT

OBJECTIVE:

People with HIV (PWH) are at greater risk of developing lung diseases even when they are antiretroviral therapy (ART)-adherent and virally suppressed. The most common pulmonary function abnormality in PWH is that of impaired diffusing capacity of the lungs for carbon monoxide (DL CO ), which is an independent risk factor for increased mortality in PWH. Earlier work has identified several plasma biomarkers of inflammation and immune activation to be associated with decreased DL CO . However, the underpinning molecular mechanisms of HIV-associated impaired DL CO are largely unknown.

DESIGN:

Cross-sectional pilot study with PWH with normal DL CO (values greater than or equal to the lower limit of normal, DL CO  ≥ LLN, N = 9) or abnormal DL CO (DL CO  < LLN, N = 9).

METHODS:

We compared the gene expression levels of over 900 inflammation and immune exhaustion genes in PBMCs from PWH with normal vs. abnormal DL CO using the NanoString technology.

RESULTS:

We found that 26 genes were differentially expressed in the impaired DL CO group. These genes belong to 4 categories 1. Nine genes in inflammation and immune activation pathways, 2. seven upregulated genes that are direct targets of the interferon signaling pathway, 3. seven B-cell specific genes that are downregulated, and 4. three miscellaneous genes. These results were corroborated using the bioinformatics tools DAVID (Database for Annotation, Visualization and Integrated Discovery) and GSEA (Gene Sets Enrichment Analysis).

CONCLUSION:

The data provides preliminary evidence for the involvement of sustained interferon signaling as a molecular mechanism for impaired DL CO in PWH.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Transducción de Señal / Infecciones por VIH / Capacidad de Difusión Pulmonar / Interferones Límite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: AIDS Asunto de la revista: SINDROME DA IMUNODEFICIENCIA ADQUIRIDA (AIDS) Año: 2024 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Transducción de Señal / Infecciones por VIH / Capacidad de Difusión Pulmonar / Interferones Límite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: AIDS Asunto de la revista: SINDROME DA IMUNODEFICIENCIA ADQUIRIDA (AIDS) Año: 2024 Tipo del documento: Article Pais de publicación: Reino Unido