In patients with hypogammaglobulinemia, doubling the standard dose of intravenous immunoglobulin significantly reduced the number and duration of infections.

Fc gamma RIIa (CD32) is the sole IgG Fc receptor capable of interaction with human IgG2, the main IgG subclass of bacterial capsular polysaccharides. The two genetically determined allotypes of human Fc gamma RIIa, Fc gamma RIIa-R131 and IIa-H131 alleles, have functionally different reactivities with human IgG2. The capacity of polymorphonuclear leukocytes (PMNL) homozygous for Fc gamma RIIa-H/H131 for IgG2 opsonized bacteria is significantly higher than phagocytosis by PMNL homozygous for Fc gamma RIIa-R/R131, independent of the Fc gamma RIIb-NA1/NA2 (CD16) allelic polymorphism. To test the clinical significance of these Fc gamma R polymorphisms, Fc gamma RIIa and Fc gamma RIIIb phenotypes of 48 children with recurrent bacterial respiratory tract infections were determined. Fc gamma RIIa-H/H131 was less than half that observed in 123 healthy adults (P = .01). IgG2 responses were low in 25 of 48 patients after immunization with pneumococcal vaccine. These results suggest that Fc gamma RIIa polymorphism may contribute to increased susceptibility to infections with encapsulated bacteria in a childhood population with low IgG2 anti-carbohydrate antibodies.

Human immunoglobulin G (IgG) Fc receptor IIa (Fc␥RIIa; CD32) is expressed on phagocytes, triggers phagocytosis, and represents the sole Fc receptor for IgG (Fc␥R) capable of interaction with IgG2, the main IgG subclass induced in response to bacterial capsular polysaccharides. The two genetically determined structurally different allotypes of human Fc␥RIIa, the products of the Fc␥RIIa-R131 and IIa-H131 alleles, have functionally different reactivities with human IgG2. In humans, the Fc␥RIIa-H131 allotype is known to interact efficiently with complexed human IgG2, whereas the IIa-H131 allotype does so only poorly. This polymorphism may therefore have implications for IgG2-mediated phagocytosis of encapsulated bacteria and susceptibility to bacterial infections. Phagocytosis of IgG2-opsonized bacteria by homozygous Fc␥RIIa-R/R131, heterozygous IIa-H/R131, and homozygous IIa-H/H131 polymorphonuclear cells (PMN) was compared. A higher phagocytic capacity of IgG2-opsonized group B type III streptococci by PMN of homozygous H/H131 individuals compared with PMN from homozygous R/R131 individuals was observed (P ‫؍‬ 0.001), while heterozygous IIa-H/R131 PMN showed intermediate phagocytosis. In this model system, IgG2-mediated phagocytosis was independent of the Fc␥RIIIb-NA1/NA2 allelic polymorphism. Fc receptors for immunoglobulin G (IgG) (Fc␥R) form an essential bridge between the humoral branch and the effector cells of the immune system. They are involved in multiple biological processes, including phagocytosis, antibody-dependent cellular cytotoxicity, and release of inflammatory mediators (36, 48). In humans, three major classes of Fc␥R are recognized: Fc␥RI (CD64), Fc␥RII (CD32), and Fc␥RIII (CD16). These can be distinguished from one another on the basis of size, primary structure, monoclonal antibody (MAb) reactivity, affinity and specificity for ligands, and cellular distribution pattern. Fc␥RI represents a high-affinity receptor capable of binding monomeric human IgG1, IgG3, and IgG4. Fc␥RII and-III are low-affinity receptors, interacting only with IgG in complexed or aggregated form. Both Fc␥RII and-III interact with human IgG1 and IgG3, whereas Fc␥RII is the sole Fc␥R class capable of binding human IgG2 complexes (32, 50). Human neutrophils (PMN) constitutively express two Fc␥R: Fc␥RIIa, with a classical membrane-spanning domain and cytoplasmic tail, and Fc␥RIIIb, which is linked to the cell membrane via a glycosyl-phosphatidylinositol anchor. Both these receptors exhibit genetically determined structural and functional polymorphisms, the biallelic Fc␥RIIa-R131 and-H131 polymorphism (previously known as the high-responder [HR]/

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