Abstract • 67

S. pneumoniae (S. pn) is one of the major pathogens in upper and lower respiratory tract infections in children. In most children with recurrent respiratory tract infections, no overt immunodeficiency is found, although low total IgA and IgG2 serum levels are observed in 15-25% of these patients. Furthermore, 5 to 15% of the patients fail to make antipneumococcal (anti-pnc) antibody responses upon vaccination with pneumococcal polysaccharide (PPS) vaccine. However, despite "normal" total anti-pnc antibody responses in the remaining 85-95% of these children and normal total serum IgA and IgG2 levels, many children show abnormalities in the immune response upon PPS vaccine when IgM, IgG1, IgG2 and IgA anti-pnc responses are analysed in more detail. It was then observed that, although IgG1 and IgM antibody titers are relatively similar to adult responses, while anti-pnc IgA and IgG2 antibody responses are very low as compared to controls. The possible value of IgG2 anti-pnc antibodies in the defense against infections with pneumococci, is emphasized in in vitro studies of S.pn phagocytosis by PMN. We found the efficacy of phagocytosis of serum-opsonized S.pn to be primarily related to IgG2 anti-pnc antibody titers. Furthermore, phagocytosis of S. pn is primarily dependent on the FcγIIa-receptor (CD32) expressed on phagocytic cells, with a minor contribution of FcγRIIIb (CD16). In our assay, phagocytosis is independent of serum complement levels. We recently developed a FcγRIIa-transfected cell line that proved to be an excellent read-out model for testing opsonic antibodies in patients sera. Furthermore, the FcγRIIa structural and functional polymorphism (FcγRIIa-H131/R131) affects serum-opsonized S. pn phagocytosis. Last but not least, we found the allelic functional polymorphism of the "IgG receptor for IgG2" - FcγRIIa (CD32) - to contribute to the susceptibility for bacterial upper respiratory tract infections in children. These and other data point to a relevant role for anti-pnc IgG2 antibodies and to a role of FcγRIIa polymorphism in infectious disease. The role of FcγRIIa polymorphism is also illustrated in infectious diseases as meningococcal sepsis/meningitis. These and other data will be discussed.