Serum IgA isotypes are associated with percent emphysema, wall thickness and lung function decline

Area of Science:

• Pulmonary Medicine
• Immunology
• Radiology

Background:

• Immunoglobulin A (IgA) deficiency is a rare genetic trait linked to lung issues like emphysema and infections.
• The precise impact of IgA levels on lung structure and function remains unclear.

Purpose of the Study:

• To investigate the association between serum IgA levels and lung structure/function.
• To explore the role of galactose-deficient IgA1 (Gd-IgA1) in airway dimensions and lung function decline.

Main Methods:

• Serum IgA, IgA1, and Gd-IgA1 levels were measured in the Multi-Ethnic Study on Atherosclerosis (MESA) cohort.
• Lung structure (emphysema, airway dimensions) was assessed using CT scans, and lung function via spirometry.
• Mendelian randomisation and replication analyses in SPIROMICS were performed to confirm findings.

Main Results:

• Lower serum IgA levels correlated with increased percent emphysema, a finding supported by Mendelian randomisation.
• Higher Gd-IgA1 levels were associated with increased airway wall thickness.
• Elevated Gd-IgA1 levels were also linked to a decline in forced expiratory volume in one second (FEV1) and FEV1/FVC ratio.

Conclusions:

• Reduced serum IgA levels are associated with greater emphysema severity, suggesting a protective role in emphysema pathogenesis.
• Increased Gd-IgA1 levels are linked to airway wall thickening and reduced lung function, indicating a potentially detrimental role in airway diseases.