Quantitative analysis of immunoglobulin G subclass responses to Pseudomonas aeruginosa antigens in cystic fibrosis.

The four subclasses of IgG have different structures, functions and implications in the antibody response. IgG subclass reactions to individual Pseudomonas aeruginosa structural antigens in 22 adolescents and young adults with cystic fibrosis (CF) were studied qualitatively and quantitatively by densitometric analysis of Western blot assays. These patients had been infected by P. aeruginosa for 7 years or longer and were divided into two groups according to their pulmonary status: Group 1 comprised 11 patients with relatively good pulmonary status; Group 2 consisted of 11 patients with poor pulmonary status. There was a relative decrease of IgG1 and a relative increase of IgG2 and, especially, of IgG3 and IgG4 antibodies against P. aeruginosa antigens in the CF patients. Comparison of the two CF patient groups showed a significant increase in the proportion of IgG3 in the Group 2 patients. This could be a potential cause or effect in the deterioration of their pulmonary function. Densitometric analysis of Western blots revealed more than 24 P. aeruginosa antigens and indicated those that were the targets of the isotype antibody response(s) that were apparently most harmful. Thus, there was a significant increase of IgG2 or IgG3 reactivity (or of both) against proteins F, H (H1 and H2), and I in the Group 2 patients. One other striking observation of this study was the high reactivity of IgG4 antibodies to protein H. IgG4 was the major antibody to this protein in seven of the 11 Group 1 patients compared to two of the 11 in Group 2. We hypothesise that IgG4 antibodies may antagonise IgG2 antibodies, helping to preserve stable pulmonary function.