Lack of a Requirement for the Fc Region of IgG in Restoring Pneumococcal Opsonization via the Alternative Complement Pathway in Sickle Cell Disease

Abstract

Children with sickle cell disease have reduced serum opsonization of Streptococcus pneumoniae. Our previous studies have suggested that opsonization mediated by both the alternative and classic complement pathways is reduced because of a deficiency of IgG antibodies to pneumococcal capsular polysaccharide. This study compares the ability of purified IgG (fractionated from goat antiserum to pneumococcal capsular polysaccharide) and F(ab′)₂ fragments of the IgG preparation to restore alternative pathway-mediated opsonizaton of S. pneumoniae to sera from patients with sickle cell disease. Both the whole IgG preparation and F(ab′)₂ fragments of this preparation restored opsonization to normal levels and concomitantly increased alternative pathway-mediated deposition of C3 onto the pneumococci to a supranormallevel. These results suggest that enhancement of opsonization is mediated by the F(ab′)₂ region of IgG antibody to capsular polysaccharide and is associated with an increase in complement deposition on the bacterial surface.