Clinical significance of IgG2 deficiency in Bronchiectasis

Abstract

Bronchiectasis is a common chronic debilitating respiratory condition with patients suffering chronic cough, sputum production and recurrent chest infections. Specific immune defects can be associated with bronchiectasis in up to 10% of patients. There are four Immunoglobulin G subclasses (IgG1, IgG2, IgG3 and IgG4). IgG2 primarily binds carbohydrates found in the bacterial outer membrane and capsules, which makes IgG2 an important part of the pulmonary defence against gram positive and negative bacteria. IgG2 deficiency is the most frequently identified in patients with bronchiectasis but its clinical significance is not known. We assessed bronchiectasis patients in the bronchiectasis clinic that had IgG2 deficiency and matched patients that were IgG2 replete. Furthermore serum neutrophil phagocytosis assays of PAO1 were performed and compared between the groups. Information of 27 IgG2 deficient patients and 27 patients with normal IgG2 levels were matched for statistical analysis and comparison, which showed that 67% of deficient patients and 56% of control patients are chronically infected with pathogenic organisms. The most common bacterial pathogens isolated were: Haemophilus influenzae, Pseudomonas aeruginosa, Coliforms, Staphylococcus aureus, Streptococcus pneumoniae and Moraxella catarrhalis. There was no significant difference in age, body mass index, smoking status, lung function, CT score and sputum purulence between the deficient and the non-deficient patient group. In deficient patients, there were significantly lower IgG2 levels and the IgG2 percentage of the total IgG, with an increased Bronchiectasis Severity Index score, an increased frequency of chronic infection with Pseudomonas aeruginosa and Coliforms and an increased number of exacerbations. The phagocytosis assays showed no significant difference between the two groups. In conclusion, IgG2 deficient patients had a more severe phenotype with increased chronic infection with Pseudomonas species and increased exacerbations. Preliminary investigations show the same peripheral neutrophil phagocytic capacity for PAO1 but further work is needed to explore this further.