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Relationship between Fc receptor IIA polymorphism and infection in children with sickle cell disease
C F Norris1, S Surrey, G R Bunin
1Department of Pedlatrics, Children's Hospital of Philadelphia, Pennsylvania 19104, USA.
Insights
The Fc gamma RIIA H/H131 genotype is more common in children with sickle cell disease and Haemophilus influenzae type b infections. This finding contrasts with expectations for encapsulated organism infections in this vulnerable population.
Area of Science:
- Immunogenetics
- Pediatric Infectious Diseases
- Hematology
Background:
- Encapsulated organisms cause significant morbidity and mortality in children with sickle cell disease, even with prophylaxis.
- Fc receptors are crucial for clearing encapsulated organisms.
- The Fc gamma RIIA receptor's His(H)-Arg(R) polymorphism at amino acid 131 affects IgG2 binding and infection risk in non-sickle cell disease populations.
Purpose of the Study:
- To investigate the association between the Fc gamma RIIA receptor genotype and encapsulated organism infection in children with sickle cell disease.
- To test the hypothesis that the high-affinity human IgG2 binding genotype (H/H131) is underrepresented in infected children with sickle cell disease.
Main Methods:
- Genomic DNA was analyzed from 60 black children with sickle cell disease and a history of encapsulated organism infection.
- Fc gamma RIIA genotypes were identified using polymerase chain reaction and sequence analysis.
- Genotype distributions were compared to ethnically matched control subjects.
Main Results:
- The H/H131 Fc gamma RIIA genotype was overrepresented in children with sickle cell disease (p = 0.046).
- This overrepresentation was particularly significant in the 11 children with Haemophilus influenzae type b infection (64% H/H131 vs. 14% in controls, p = 0.002).
- No significant difference in genotype distribution was observed for Streptococcus pneumoniae infections.
Conclusions:
- The Fc gamma RIIA H/H131 genotype is overrepresented in black children with sickle cell disease who have experienced Haemophilus influenzae type b infections.
- This genetic predisposition is specific to H. influenzae type b and not observed for S. pneumoniae infections in this cohort.
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.