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Augmentation Therapy Modulates Systemic Inflammation in Individuals with Alpha-1 Antitrypsin Deficiency and Chronic
J Lascano1, L Riley2, N Khodayari1
1University of Florida, Department of Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, Gainesville, Florida, United States.
Chronic Obstructive Pulmonary Diseases (Miami, Fla.)
|June 26, 2023
Summary
Alpha-1 antitrypsin (AAT) deficiency in COPD patients shows higher C-reactive protein (CRP) levels, indicating systemic inflammation. Augmentation therapy for AAT deficiency reduces CRP, suggesting a benefit in managing inflammation.
Area of Science:
- Pulmonary Medicine
- Genetics
- Immunology
Background:
- Alpha-1 antitrypsin (AAT) deficiency is a genetic disorder linked to chronic obstructive pulmonary disease (COPD).
- AAT is a protease inhibitor with anti-inflammatory properties, and its deficiency can lead to increased systemic inflammation.
- Investigating C-reactive protein (CRP) levels in AAT-deficient individuals with COPD can elucidate the extent of systemic inflammation.
Purpose of the Study:
- To assess plasma C-reactive protein (CRP) levels in individuals with Alpha-1 antitrypsin (AAT) deficiency and COPD.
- To determine if AAT augmentation therapy impacts CRP levels and systemic inflammation.
- To explore the correlation between lung function and CRP levels in AAT-deficient COPD patients.
Main Methods:
- Recruited AAT-deficient individuals and a matched control cohort.
- Determined AAT genotypes using a Taqman-based assay.
- Measured plasma AAT and CRP levels via nephelometry and analyzed using unpaired t-tests and Pearson's correlation.
Main Results:
- AAT-deficient participants (n=742) had significantly different AAT and CRP levels compared to controls (n=40).
- AAT-deficient individuals receiving augmentation therapy showed lower CRP levels (0.32±0.53mg/dL) than those not receiving it (0.69±1.97mg/dL).
- A negative correlation was observed between forced expiratory volume in 1 second (FEV1) and CRP in AAT-deficient individuals without augmentation therapy.
Conclusions:
- AAT-deficient individuals with COPD exhibit elevated circulating CRP, indicative of heightened systemic inflammation.
- AAT augmentation therapy is associated with reduced plasma CRP levels in these patients.
- The findings suggest that augmentation therapy may help mitigate systemic inflammation in AAT-deficient COPD.
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