Adrien Bouglé1, Adeline Max1, Nicolas Mongardon1, David Grimaldi2, Frédéric Pène2, Christophe Rousseau3, Jean-Daniel Chiche2, Jean-Pierre Bedos4, Eric Vicaut5, Jean-Paul Mira6. 1. Paris Descartes University, Paris; Medical Intensive Care Unit, Cochin University Hospital, Assistance Publique-Hôpitaux de Paris, Paris. 2. Paris Descartes University, Paris; Medical Intensive Care Unit, Cochin University Hospital, Assistance Publique-Hôpitaux de Paris, Paris; Cochin Institute, INSERM U1016/CNRS UMR8104, Paris. 3. Cochin Institute, INSERM U1016/CNRS UMR8104, Paris. 4. Intensive Care Unit, André Mignot Hospital, Le Chesnay, France. 5. Paris Diderot University, Paris; Department of Biophysics, Lariboisière University Hospital, Assistance Publique-Hôpitaux de Paris, Paris. 6. Paris Descartes University, Paris; Medical Intensive Care Unit, Cochin University Hospital, Assistance Publique-Hôpitaux de Paris, Paris; Cochin Institute, INSERM U1016/CNRS UMR8104, Paris. Electronic address: jean-paul.mira@cch.aphp.fr.
Abstract
BACKGROUND: Streptococcus pneumoniae is a major cause of pneumonia and meningitis. Several genetic polymorphisms have been described to explain differences in susceptibility and severity of encapsulated pathogen-related diseases. Among them, a functional FCGR2A polymorphism leading to amino acid change of histidine (H) to arginine (R) at position 131 appears to be a major candidate in adult invasive pneumococcal diseases (IPDs). However, previous reports need confirmation in a large, well-defined population. METHODS: This prospective genetic association study was carried out in a 24-bed medical ICU of a tertiary teaching hospital over 7 years. DNA from all white patients with IPD (pneumonia or meningitis) was genotyped for the FcγRIIa-R/H131 polymorphism. RESULTS: A total of 243 patients with IPD were enrolled; 202 (82%) had pneumonia, and 55 (22%) had meningitis. Mean age was 61 years, and mean Simplified Acute Physiology Score II was 50.4. One-half of the patients had bacteremia, and 84% of the cohort received mechanical ventilation. The hospital mortality rate was 31%. In the IPD group, the distribution of the FcγRIIa-R/H131 genotypes (H/H, 25%; H/R, 53%; R/R, 22%) was comparable with that in the white control group. Comparison of the FcγRIIa-R/R131 and the FcγRIIa-R/H131 + FcγRIIa-H/H131 groups did not demonstrate any difference for age, Simplified Acute Physiology Score II, origin of sepsis, and other comorbid conditions. However, the variant FcγRIIa-R/R131 genotype was independently associated with decreased hospital mortality (OR, 0.251; 95% CI, 0.098-0.645; P = .004). CONCLUSIONS: In a well-defined population of patients with IPD, the frequency of the variant FcγRIIa-R131 does not differ from that of other critically ill patients. However, the FcγRIIa-R/R131 genotype was independently associated with increased survival, regardless of site of infection.
BACKGROUND:Streptococcus pneumoniae is a major cause of pneumonia and meningitis. Several genetic polymorphisms have been described to explain differences in susceptibility and severity of encapsulated pathogen-related diseases. Among them, a functional FCGR2A polymorphism leading to amino acid change of histidine (H) to arginine (R) at position 131 appears to be a major candidate in adult invasive pneumococcal diseases (IPDs). However, previous reports need confirmation in a large, well-defined population. METHODS: This prospective genetic association study was carried out in a 24-bed medical ICU of a tertiary teaching hospital over 7 years. DNA from all white patients with IPD (pneumonia or meningitis) was genotyped for the FcγRIIa-R/H131 polymorphism. RESULTS: A total of 243 patients with IPD were enrolled; 202 (82%) had pneumonia, and 55 (22%) had meningitis. Mean age was 61 years, and mean Simplified Acute Physiology Score II was 50.4. One-half of the patients had bacteremia, and 84% of the cohort received mechanical ventilation. The hospital mortality rate was 31%. In the IPD group, the distribution of the FcγRIIa-R/H131 genotypes (H/H, 25%; H/R, 53%; R/R, 22%) was comparable with that in the white control group. Comparison of the FcγRIIa-R/R131 and the FcγRIIa-R/H131 + FcγRIIa-H/H131 groups did not demonstrate any difference for age, Simplified Acute Physiology Score II, origin of sepsis, and other comorbid conditions. However, the variant FcγRIIa-R/R131 genotype was independently associated with decreased hospital mortality (OR, 0.251; 95% CI, 0.098-0.645; P = .004). CONCLUSIONS: In a well-defined population of patients with IPD, the frequency of the variant FcγRIIa-R131 does not differ from that of other critically ill patients. However, the FcγRIIa-R/R131 genotype was independently associated with increased survival, regardless of site of infection.
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Authors: Hervé Ghesquières; Beth R Larrabee; Corinne Haioun; Brian K Link; Aurélie Verney; Susan L Slager; Nicolas Ketterer; Stephen M Ansell; Richard Delarue; Matthew J Maurer; Olivier Fitoussi; Thomas M Habermann; Fréderic Peyrade; Ahmet Dogan; Thierry J Molina; Anne J Novak; Hervé Tilly; James R Cerhan; Gilles Salles Journal: Hematol Oncol Date: 2016-06-10 Impact factor: 5.271