Avidity of anti-P aeruginosa antibodies during chronic infection in patients with cystic fibrosis

Abstract

Background-In order to study the impact on the lung function of patients with cystic fibrosis of the avidity of antipseudomonal antibodies, the avidity of antibodies against the chromosomal -lactamase of Pseudomonas aeruginosa (a ab) and against the 60-65 kDa heat shock protein of P aeruginosa (antiGroEL) were measured in serum samples collected longitudinally during chronic infection with P aeruginosa from a group of patients with poor and good lung function. Methods-Thethiocyanate elution method in which the molarity of potassium thiocyanate required to elute 50% bound antibody under conditions of antigen excess in ELISA was used to measure the relative avidity. Results-All patients developed increasing levels of a ab and anti-GroEL antibodies during the follow up period but no maturation of the avidity of these antibodies was observed. In patients with good lung function the avidity of a ab was higher than in patients with poor lung function (p = 0.018). No significant diVerence in the avidity of the anti-GroEL antibodies was observed between the two groups of patients. Conclusion-In patients with cystic fibrosis a high avidity of a ab could contribute to a more eYcient inhibition of the -lactamase by these antibodies, resulting in the better lung function seen in this group. The immunopathological implication of the failure in avidity maturation of antibodies in chronic infection is discussed.

Host response to Staphylococcus aureus cytotoxins in children with cystic fibrosis

“…Interestingly, this response was not seen in the sera of patients with CF. This lack of expected affinity maturation has been described previously for the humoral response to Pseudomonas aeruginosa in subjects with cystic fibrosis 31 . Whether this is related to differences in the CF host, differences in the pathogen, or differential expression of antigens during colonization of the CF lung remains unclear but warrants further investigation.…”

The immune system vs.Pseudomonas aeruginosabiofilms

“…Interestingly, and in contrast to what is usually reported during the course of an infection, there was no maturation in avidity (binding strength between antibody and antigen) of antibodies directed against chromosomal β‐lactamase of P. aeruginosa or the P. aeruginosa heat shock protein Gro‐EL during an 11‐year follow‐up period of the chronic P. aeruginosa lung infection in CF (Ciofu et al , 1999). In accordance, other investigators have reported the development of reduced opsonic killing by antibody responses directed against P. aeruginosa exopolysaccharide (Meluleni et al , 1995).…”

Recent developments for Pseudomonas vaccines

“…During chronic lung infections in affected CF individuals, high levels of antibodies against components of P. aeruginosa such as surface O-polysaccharides and mucoexopolysaccharides are present, but they have poor opsonic activity and cannot clear the infection. 9,10 Furthermore, the mucoid phenotype resists to the opsonic killing by antibodies because of the biofilm formation. 11 High antibody titers have been associated with more severe lung disease.…”