Immunoglobulin allotypes and IgG subclass antibody response to Aspergillus fumigatus in cystic fibrosis patients

Abstract

Background: A majority of patients with cystic fibrosis (CF) become colonised with Aspergillus fumigatus ( Af.), but only a minority develops allergic bronchopulmonary aspergillosis (ABPA). ABPA is associated with increased levels of specific immunoglobulin G (IgG) anti- Af. antibodies with a characteristic IgG subclass distribution. We examined whether this characteristic immune response was under the influence of GM and KM allotypes, which are genetic markers (antigenic determinants) on gamma- and kappa-light chains, respectively. Methods: Sera from 233 CF patients were typed for seven GM determinants and two KM determinants. The types were correlated to IgG subclass anti- Af. antibody levels and to the presence or absence of Af. colonisation as well as ABPA. Results: The IgG2 antibody level was significantly higher in heterozygous GM (1,2,17 23 5,21 and 1,3,17 23 5,21) compared to homozygous GM allotypes ( p=0.02). Patients with the same allotypes tended to have higher IgG1 ( p=0.051). In patients with ABPA, being heterozygous for G1M and G3M was linked to higher IgG4 and lower IgG3 as compared to the other genotypes. The KM markers did not influence the antibody levels. The allotype GM(3 23 5), associated with atopic bronchial asthma, tended to make a relatively larger group in ABPA patients compared to non-ABPA and patients not colonised with Af. ( p=0.09). Conclusions: An influence of the GM allotypes on the immune response to Af. and on the development of ABPA in patients with CF is suggested.