The carbohydrate content of IgG from patients with cystic fibrosis

We compare the complete carbohydrate composition of IgG purified from the serum of patients with cystic fibrosis (CF) with that of control subjects. Our results indicate that IgG from cystic fibrosis patients is underglycosylated with respect to galactose and sialic acid, the two terminal sugars on the antennae of the complex-type oligosaccharide chains found on IgG. The galactose content, as determined by gas liquid chromatography, was 2.81 +/- 0.86 (S.D.) mole/mole of IgG for normal subjects versus 1.5 +/- 0.39 for CF subjects (P less than 0.025). Sialic acid content, as determined by the Warren procedure, was 1.33 +/- 0.39 for normals versus 0.47 +/- 0.10 for CF subjects (P less than 0.001). Neither galactose nor sialic acid values for the two groups overlapped. The contents of the core sugars, mannose and glucosamine, and of fucose were not significantly different. When the data are expressed as residues per 3 moles mannose, similar results are obtained. We suggest that immune complex formation, which has been documented in many CF patients, exposes sugar chains of IgG molecules to hydrolytic activity of serum glucosidases, resulting in partial removal of the more peripheral sugars. Because serum glycoproteins missing sialic acid and galactose are not readily cleared from the circulation, the observed changes may contribute to elevated levels of IgG and immune complexes in older people with CF.