MedWire News: Carriers of the minor allele of a polymorphism in the FCGR2A gene, which encodes CD32, are substantially less likely to die from invasive pneumococcal disease (IPD) than those with the major allele, French researchers report.
In their study of 243 White patients with IPD (pneumonia and/or meningitis), Jean-Paul Mira (Cochin University Hospital, Paris) and colleagues found that the in-hospital mortality rate was 14.8% among patients with the FcγRIIa-R/R131 genotype, compared with 35.6% for those carrying FcγRIIa-H/H131 or FcγRIIa-R/H131.
Interestingly, FcγRIIa-R/R131 has a weaker binding capacity for immunoglobulin G2 - the most important natural antibody isotype specifically directed against encapsulated bacteria such as Streptococcus pneumonia - than the "wild-type" receptor FcγRIIa-H131.
This suggests that the variant has an "apparent paradoxical protective role" against S. pneumoniae infection, say the researchers.
To confirm previous reports of a protective role of the FCGR2A polymorphism, Mira and team genotyped patients admitted to an intensive care unit over a 7-year period.
They found that the genotype distribution was similar between the patients with IPD (H/H=25%; H/R=53%; R/R=22%) and a control group of 2789 patients without any sort of infection (H/H=26%; H/R=49%; R/R=25%).
There was also no difference in genotype distribution by age, disease severity (Simplified Acute Physiologic Score 2), origin of sepsis, and other co-morbid conditions.
Multivariate analysis, adjusted for age, gender, and disease severity, revealed that patients homozygous for the minor R allele had a 68% reduced risk for in-hospital death compared with heterozygous patients and those homozygous for the H allele.
Of the patients with IPD, 202 (82%) were admitted for pneumonia, while 55 (22%) had meningitis. However, the effect of the mutation did not differ significantly in the presence or absence of meningitis infection, at respective odds ratios of 0.23 and 0.26. Nor did it differ in the presence or absence of bacteremia, at respective odds ratios of 0.36 and 0.16.
The researchers note that the study cohort had particularly severe disease, with around half having bacteremia and 84% mechanically ventilated.
They conclude in Chest: "Carrying the FcγRIIa-R/R131 genotype is protective during IPD."
MedWire (www.medwire-news.md) is an independent clinical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2012