Interferon-signaling pathways are upregulated in people with HIV with abnormal pulmonary diffusing capacity (DL CO )

Area of Science:

• Pulmonology
• Immunology
• Genetics

Background:

• People with HIV (PWH) face increased lung disease risk, even with effective antiretroviral therapy (ART) and viral suppression.
• Impaired diffusing capacity of the lungs for carbon monoxide (DL CO) is common in PWH and linked to higher mortality.
• Molecular mechanisms behind HIV-associated impaired DL CO remain largely unknown.

Purpose of the Study:

• To investigate gene expression differences in people with HIV (PWH) with normal versus impaired DL CO.
• To identify potential molecular pathways contributing to impaired DL CO in PWH.

Main Methods:

• A cross-sectional pilot study compared gene expression of over 900 inflammation and immune exhaustion genes in PBMCs.
• Participants included PWH with normal DL CO (N=9) and abnormal DL CO (N=9).
• NanoString technology was used for gene expression analysis, with results corroborated by DAVID and GSEA bioinformatics tools.

Main Results:

• Twenty-six genes were differentially expressed in the impaired DL CO group.
• Key findings include upregulated interferon signaling pathway genes and downregulated B-cell specific genes.
• Inflammation and immune activation pathways were also represented among the differentially expressed genes.

Conclusions:

• Sustained interferon signaling is implicated as a potential molecular mechanism for impaired DL CO in PWH.
• These findings offer preliminary insights into the pathogenesis of lung disease in PWH.
• Further research is warranted to elucidate these molecular pathways fully.