Direct evidence that decreased serum opsonization of Streptococcus pneumoniae via the alternative complement pathway in sickle cell disease is related to antibody deficiency.

Abstract

Two approaches were used to demonstrate that reduction in serum opsonization of Streptococcus pneumoniae via the alternative complement pathway in children with sickle cell disease is related to a deficiency of antibodies to pneumococcal capsular polysaccharide. First, opsonization of S. pneumoniae mediated by the alternative pathway in patients' sera was restored to normal by addition of the purified IgG or IgM fraction of goat antiserum to capsular polysaccharide of the homologous serotype. Secondly, IgG antibody titers to capsular polysaccharide in patients' sera correlated significantly with alternative pathwaymediated opsonization; the correlation between titers of IgM anticapsular antibodies and opsonization approached statistical significance. The sum of the IgG and IgM anticapsular antibody titers correlated most significantly with opsonization. Our results suggest that reduction in alternative pathway-mediated opsonization in sera from children with sickle cell disease is related to low levels of both IgG and IgM anticapsular antibodies.

Relationship ofin vitrophagocytosis of serotype 14Streptococcus pneumoniaeto specific class and IgG subclass antibody levels in healthy adults

“…Similar lack of association has been reported by Chudwin et al, [14] and by Bjornson & Lobel [13]. Very little is known about the possible role of specific IgA antibody in preventing pneumococcal infection.…”

“…Correlation between specific IgGl antibody and phagocytosis of serotype 14 pneumococcus, as shown in this study, has been noted for serotype lOA in children with sickle cell disease [13], and for serotypes 8,9 and 19 in healthy adults [5]. However, the latter study demonstrated no association with specific IgG2 antibody, and the best correlation was with antibody of the IgG4 subclass.…”

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

“…Nonetheless, our data demonstrate that 1A2, which protects 40% of F2, 30% of C4 Ϫ/Ϫ , and 40% of FB ϩ/ϩ mice but no FB Ϫ/Ϫ mice, is not as protective as either 7C5 or A7. C3 deposition on the pneumococcal surface via the alternative pathway is a function of antibody specificity in that it requires the F(abЈ) 2 but not the Fc region of PPS-specific antibodies (5,6). Our data support the concept that the most protective antibodies might be distinguished from less protective and/or nonprotective antibodies by reactivity with defined PPS-3 epitopes.…”

Immunoglobulin Isotype-Specific Antibody Responses to Pneumococcal Polysaccharide Vaccine in Patients with Recurrent Bacterial Respiratory Tract Infections

“…Apart from 5/46 patients of group I and 6/15 patients of group 11, all patients showed anti-pneumococcal IgM levels to both strongly and weakly immunogenic serotypes. The function of IgM may be mainly bactericidal via complement-mediated lysis, but IgM is probably less effective than IgG in both opsonization (Hib) (41,42) and protection from pneumococcal disease (31,43). Several investigators failed to demonstrate a significant correlation between IgM anti-pneumococcal antibodies and opsonic activity (31,43) The frequent combination of low IgG2 and IgA antipolysaccharide antibody responses in childhood patients with recurrent bacterial infections suggests a shared common underlying mechanism in the regulation of expression of the heavy chain genes.…”