Correlation Between Alpha-1-Antitrypsin Levels and Bronchiectasis in Humoral Immunodeficiency Patients Receiving Gammaglobulin Infusions

Abstract

When Alpha-1-antitrypsin (AAT) is low or deficient, it can be associated with bronchiectasis, a chronic inflammatory lung disease. Bronchiectasis is also seen in humoral immunodeficiency states such as Common Variable Immunodeficiency (CVID) and hypogammagloblinemia (Hypogam). In patients with CVID/Hypogam, the progression of bronchiectasis has been known to occur even in the absence of recurrent infections and while the patient is receiving adequate treatment. Both the AAT levels as well as AAT phenotypic (P) variation and their potential correlation between CVID/Hypogam patients with or without bronchiectasis has not been studied. Our hypothesis is: Patients with humoral immunodeficiencies and bronchiectasis have lower levels of AAT compared to those without bronchiectasis. 154 Patients with CVID/Hypogam, both with and without bronchiectasis, requiring IVIG were screened for their AAT levels and phenotype during their routine IgG nadir levels. High Resolution chest CT scans of patients were obtained and compared with AAT levels and phenotype. Patients without bronchiectasis were found to have higher levels of AAT (PM) than those with bronchiectasis (32.66 vs. 31.62, P0.02). Furthermore patients with improved/resolved bronchiectasis since initiating IVIG had higher levels of AAT (PM) than those with worsening bronchiectasis (33.21 vs. 31.36, P0.005). The prevalence of AAT mutation phenotypes was 1:11 vs. 1:17 reported in the general public. Higher levels of AAT (PM) correlate with CVID/Hypogam patients requiring IVIG who are without or improving bronchiectasis, than those that have lower levels and stable or worsening bronchiectasis. The prevalence of AAT mutations is higher in these patients then in the general public.