The lung proteome in HIV-associated obstructive lung disease

Area of Science:

• Pulmonology
• Immunology
• Proteomics

Background:

• Obstructive lung disease (OLD) is a growing concern for people living with HIV (PLWH).
• Current biomarkers for identifying individuals at risk of developing HIV-associated OLD are lacking.
• The underlying biological mechanisms of HIV-associated OLD, independent of smoking, are not fully understood.

Purpose of the Study:

• To identify potential biomarkers for obstructive lung disease (OLD) in persons living with HIV (PLWH).
• To elucidate the biological pathways associated with HIV-associated OLD.
• To utilize a comprehensive proteomic approach for biomarker discovery.

Main Methods:

• Proteomic analysis using tandem mass tagging and mass spectrometry (MS) on bronchoalveolar lavage fluid.
• Combined untargeted MS with a targeted SomaScan aptamer-based approach.
• Statistical analysis including Pearson correlation for protein-lung function association and pathway over-representation analysis.

Main Results:

• Over 3800 proteins were identified by MS.
• 254 proteins showed correlation with lung function (FEV1 % pred) after adjusting for smoking status.
• Pathway analysis highlighted cell adhesion molecules as significantly associated with OLD in PLWH.

Conclusions:

• Protein expression in the lungs of PLWH is associated with reduced lung function.
• Cell adhesion molecules are implicated in the pathogenesis of HIV-associated obstructive lung disease.
• These findings suggest potential roles for cell adhesion molecules as biomarkers and therapeutic targets.