IMPAIRED NATURAL IgG2 ANTIBODY (AB) RESPONSE TO POLYSACCHARIDE ANTIGENS AND DECREASED Km(1)–A2m(2) ALLOTYPES IN CYSTIC FIBROSIS (CF)

Abstract

We recently described impaired IgG2 Ab responses to P. aeruginosa (PA) lipopolysaccharide in CF patients without PA infection (Pediatr Res 20:453, 1986). To investigate the basis for this defect, we measured natural IgG and IgG1-4 Ab levels to H. influenzae polyribophosphate (PRP) and tetanus toxoid (TT) by quantitative monoclonal Ab-based ELISA in 24 adult CF patients and 20 controls. Immunoglobulin allotypes were determined on 154 CF patients and 110 controls. The TT IgG Ab response was predominantly IgG1. CF and control subjects had similar TT IgG and IgG1 Ab levels. The PRP IgG Ab response was predominantly IgG2. In contrast to TT results, CF patients had subnormal levels of PRP IgG Ab compared to normal (geometric mean = 1.14 vs 2.32 meg/ml, respectively, 2 tailed p=0.004, Mann Whitney U test). PRP IgG2 levels were also depressed in CF patients (p=0.03). CF patients had a lower prevalence of Km(1) (p<0.025, X2 with continuity correction) and A2m(2) (p<0.05) than controls: G2m(n) and other allotype prevalences were similar. Impaired IgG2 Ab responses to certain polysaccharide-encapsulated microbes may predispose CF patients to endobronchial infection and lead to production of nonopsonizing isotype responses. A possible immunogenetic basis for impaired IgG2 Ab response is suggested by lower Km(l) allotype prevalence, while the role of A2m(2) is unknown.