Discrepancy between Effects of in vivo and in vitro Administration of Gammaglobulin on Phagocytic Killing of <i>Streptococcus pneumonia</i><i>e</i> in an Antibody-Deficient Serum

Abstract

Phagocytic killing of Streptococcus pneumoniae serotypes 6A, 14, 18C, 19F and 23F was investigated in the dysgammaglobulinemic serum of a patient with recurrent pneumococcal infections. Previous studies with this serum had established combined IgG2, IgG4 and IgA deficiency, deficiency with regard to specific antipolysaccharide antibodies and essentially normal complement functions. Phagocytic killing of all serotypes was reduced in the patient’s serum. Addition of immunoglobulin in vitro enhanced both classical and alternative complement pathway mediated opsonization. In constitution experiments neither purified C1q nor CRP influenced phagocytic killing. Surprisingly, intramuscular administration of a fairly small dose of gammaglobulin to the patient was associated with a rapid increase in the serum opsonic activity for serotype 23 F. The increased opsonization occurred before specific anticapsular antibodies were detectable in serum. The findings suggest that the possible effects of gammaglobulin treatment may not exclusively be related to the acquisition of serotype-specific antibodies.

Structure-Function Relationships for Human Antibodies to Pneumococcal Capsular Polysaccharide from Transgenic Mice with Human Immunoglobulin Loci

“…However, 1A2 also led to C3 deposition in vitro, albeit to a lesser extent than A7 and 7C5, but was not protective in complement-deficient mice. This finding parallels studies in which in vitro measures of antibody biological activity were insufficient to predict antibody efficacy in experimental pneumococcal infection (9,19) and suggests that in vivo studies may be more predictive of antibody efficacy than available in vitro assays. Despite being nonprotective in complement-deficient mice, 1A2 protects BALB/c mice at a 10-g dose, albeit to a lesser degree than A7 and 7C5.…”