Assessing Inflammatory Protein Biomarkers in COPD Subjects with and without Alpha-1 Antitrypsin Deficiency

Area of Science:

• Pulmonology and Respiratory Medicine
• Proteomics and Biomarker Discovery
• Genetics and Genetic Modifiers

Background:

• Alpha-1 Antitrypsin Deficiency (AATD) patients with the Pi*ZZ genotype show varied Chronic Obstructive Pulmonary Disease (COPD) risk.
• Non-smoking AATD individuals developing COPD suggest inflammatory processes contribute independently of smoking.
• The study investigates inflammatory protein biomarkers as predictors of COPD in AATD.

Purpose of the Study:

• To identify blood protein biomarkers associated with COPD in AATD patients.
• To explore the role of inflammation in COPD pathogenesis in AATD.
• To develop and validate a proteomic risk score for COPD prediction in AATD.

Main Methods:

• Analysis of participants from COPDGene (Pi*MM) and AAT Genetic Modifier Study (Pi*ZZ).
• Identification of proteins associated with FEV1/FVC, adjusting for confounders and familial relatedness.
• Construction of lung-specific protein-protein interaction networks and development of a proteomic risk score (protRS).

Main Results:

• Sixteen blood proteins associated with airflow obstruction identified, 14 highly expressed in the lung.
• Protein-protein interaction networks implicated immune system regulation and cytokine signaling.
• A proteomic risk score improved COPD prediction in AATD individuals (AUC 0.86 vs. 0.80).

Conclusions:

• Blood proteins associated with inflammatory processes predict airflow obstruction in AATD.
• Immune activation and inflammation are key modulators of COPD risk in AATD.
• Biomarkers like AGER are significant predictors of COPD in this population.