Nonspecific immunoglobulin synthesis and elevated IgG levels in rabbits immunized with mucoid exopolysaccharide from cystic fibrosis isolates of Pseudomonas aeruginosa.

Abstract

Correlations have been observed between the presence of elevated levels of serum IgG and poor clinical status in cystic fibrosis, and between colonization with mucoid exopolysaccharide (MEP)-producing strains of Pseudomonas aeruginosa and poor clinical status. To determine if P. aeruginosa products could affect the immune system in such a way as to cause nonspecific Ig synthesis and elevated IgG levels, we immunized rabbits with whole bacterial cells and purified MEP from three strains of mucoid P. aeruginosa and with cells of a mucoid strain of E. coli. Antisera raised to whole bacterial cells reacted slightly with a panel of 12 different polysaccharide antigens from various bacteria, whereas antisera raised to purified MEP reacted moderately to strongly with these antigens. The heterologous antibodies elicited by MEP generally showed high affinities and specificities for heterologous antigens, and were functional in opsonophagocytic assays. Analysis of the kinetics of rabbit responses to MEP against homologous and heterologous antigens suggested that nonspecific Ig synthesis could be documented shortly after homologous antibody to MEP was elicited. Rabbits hyperimmunized with MEP also had elevated levels of IgG, even after removal of MEP-specific antibody. These data suggest that the change in young cystic fibrosis patients from a relatively healthy, hypogammaglobulinemic state to more progressive lung disease, associated with elevated levels of IgG and colonization with mucoid P. aeruginosa, may be mediated, in part, by the effects of MEP on mammalian immune systems.