Objective: Despite penicillin prophylaxis and vaccination, infection with encapsulated organisms remains a leading cause of morbidity and death in children with sickle cell disease. The role of Fc receptors in the clearance of encapsulated organisms is well documented. The His(H)-Arg(R) polymorphism at amino acid 131 of the Fc gamma RIIA receptor alters binding affinity for human IgG2 and influences infection with encapsulated organisms in children without sickle cell disease. We hypothesized that the genotype for high-affinity human IgG2 binding (H/H131) is underrepresented in children with sickle cell disease who had encapsulated organism infection.
Design: We studied 60 black children with sickle cell disease from four participating centers who had a history of encapsulated organism infection. Genomic DNA from peripheral blood was subjected to amplification by polymerase chain reaction and to sequence analysis for identification of the Fc gamma RIIA genotype, and the genotype distribution was then compared with our data from ethnically matched control subjects.
Results: Contrary to our hypothesis, the H/H131 genotype was overrepresented in all individuals (p = 0.046) and in particular in the 11 individuals with a history of Haemophilus influenzae type b infection (64% H/H131, 27% H/R131, 9% R/R131; p = 0.002), in comparison with ethnically matched control subjects (14% H/H131, 60% H/R131, 26% R/R131). In the 51 individuals with a history of Streptococcus pneumoniae infection, the genotype distribution was not statistically significantly different from that of the control population.
Conclusions: The H/H131 Fc gamma RIIA genotype is overrepresented in black children with sickle cell disease and a history of H. influenzae type b infection but not in those with S. pneumoniae infection.