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

Abstract

Summary. The four subclasses of IgG have different structures, functions and implications in the antibody response. IgG subclass reactions to individual Pseudornonas 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 1 1 patients with relatively good pulmonary status; Group 2 consisted of 1 1 patients with poor pulmonary status. There was a relative decrease of IgGl 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 1 1 Group 1 patients compared to two of the 1 1 in Group 2. We hypothesise that IgG4 antibodies may antagonise IgG2 antibodies, helping to preserve stable pulmonary function.

Mucosal and systemic antibody responses to potentialPseudomonas aeruginosavaccine protein antigens in young children with cystic fibrosis following colonization and infection

“…29,30,39,40 In this study, a strong response was also observed to OprF for all immunoglobulin isotypes in serum, which increased with disease progression and culture positive status. In BAL, the OprF specific antibody response was most prominent in the IgA isotype.…”

“…[21][22][23][24][25][26][27] Specific antibody responses to various P. aeruginosa antigens have been studied in the sera of adult patients, however, the characterization of antibody responses in children who differ in their pulmonary clinical status during the early years of life and initial stages of infection has not been conducted. [28][29][30] A study investigating serum antibodies against alkaline phosphatase, elastase and exotoxin A in 183 CF patients (mean age 16.7 y) indicated that regular determination of serum antibody may be a useful indicative measure of probable infection for CF patients with negative or intermittent P. aeruginosa cultures. 31 As P. aeruginosa infects the mucosal surfaces of the respiratory tract, examining the mucosal immune response of young CF children could provide important complementary knowledge to concurrent systemic serology studies.…”

Association Between the IgG Subclass Response, Inflammation and Disease Status in Helicobacter pylori Infection

“…Although strains of H. pylori with enhanced virulence potential have been reported, the evidence to date does not support the hypothesis that infection with such strains is suf cient for the development of either PUD or GC. In other infections the host immune response has been shown to be important in determining the clinical outcome of infection (18)(19)(20)(21). In an attempt to further investigate factors involved in the development of more serious gastroduodenal disease we examined the relationship between the IgG subclass response to H. pylori infection and the in ammatory response and clinical disease presentation in individuals with DU disease and FD.…”

“…For example, in cystic brosis patients infected with Pseudomonas aeruginosa increased levels of IgG3 antibodies to P. aeruginosa have been associated with higher levels of in ammation and poorer pulmonary status (21).…”

“…For example, an association between speci c IgG subclass levels and different clinical manifestations of acne, mycobacterial infections and Pseudomonas aeruginosa infections have been reported (18)(19)(20)(21).…”