Bronchiectasis With Inborn Errors of Immunity: Zooming in on Predominantly Antibody Deficiencies.

Abstract

Bronchiectasis is a chronic inflammatory lung disease characterized by permanent airway dilation, mucus production, recurrent infections, and progressive structural injury. Inborn errors of immunity (IEIs), particularly predominantly antibody deficiencies (PADs), are important and potentially under-recognized causes of non-cystic fibrosis bronchiectasis (NCFB). Antibody deficiency increases susceptibility to bacterial infection, but the observation that bronchiectasis develops in only a subset of patients with PADs, and may develop despite immunoglobulin replacement therapy (IGRT), indicates that serum antibody measurements alone do not fully define the airway risk. Bronchiectasis in IEI likely reflects the interaction of impaired systemic humoral immunity impacting mucosal immune defenses, altered IgG transport or catabolism, B-cell dysregulation, T-cell and innate immune dysfunction, autoimmunity, environmental exposures, comorbid lung disease, and chronic airway infection. In this review, we summarize reported frequencies of NCFB among selected IEIs with antibody deficiency, discuss the limitations of IgG subclass and serum-based antibody testing as predictors of airway disease, and review evidence supporting higher individualized IGRT dosing in patients with antibody deficiency and bronchiectasis to achieve therapeutic IgG levels. We also propose a practical clinical framework for evaluating immune defects in bronchiectasis and for longitudinal pulmonary screening in patients with IEIs at increased risk of bronchiectasis.