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Abstract O-33: WHOLE-EXOME SEQUENCING FOR THE IDENTIFICATION OF PRIMARY IMMUNODEFICIENCY IN CHILDREN WITH SEPSIS - A PROSPECTIVE POPULATION-BASED COHORT STUDY (SWISS PEDIATRIC SEPSIS STUDY)

Schlapbach, L.J.1; Borghesi, J.2; Trueck, J.3; Asgari, S.4; Sancho-Shimizu, V.5; Agyeman, P.6; Levin, M.5; Aebi, C.6; Berger, C.3; Fellay, J.4

Pediatric Critical Care Medicine: June 2018 - Volume 19 - Issue 6S - p 15
doi: 10.1097/01.pcc.0000537375.87387.52
Oral Abstracts
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1Paediatric Critical Care Research Group- Mater Research- University of Queensland, Paediatric Intensive Care Unit- Lady Cilento Children`s Hospital, Brisbane, Australia

2Global Health Institute- School of Life Sciences, École Polytechnique Fédérale de Lausanne EPFL, Lausanne, Switzerland

3University Children’s Hospital Zurich and the Children’s Research Center, University Children’s Hospital Zurich and the Children’s Research Center, Zurich, Switzerland

4Global Health Institute- School of Life Sciences- École Polytechnique Fédérale de Lausanne EPFL, Global Health Institute- School of Life Sciences- École Polytechnique Fédérale de Lausanne EPFL, Lausanne, Switzerland

5Imperial College of London, Section of Paediatrics Division of Infectious Disease, London, United Kingdom

6Department of Pediatrics- Bern University Hospital- Inselspital- University of Bern, Department of Pediatrics- Bern University Hospital- Inselspital- University of Bern, Bern, Switzerland

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Aims & Objectives:

Life-threatening infections may represent the first manifestation of an underlying primary immunodeficiency (PID), but the role of PIDs in pediatric sepsis is largely unknown. We performed whole-exome sequencing (WES) in a national cohort of children with blood culture-proven bacterial sepsis to characterize the contribution of PID in pediatric sepsis.

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Methods

Population-based prospective study including previously healthy children ≥28days and <17years admitted with community-acquired blood culture-proven sepsis caused by S. aureus, S. pneumoniae, S. pyogenes, H. influenzae, N. meningitidis or S. agalactiae between 2011-09-01 and 2015-12-31. Analysis of WES data was restricted to rare variants (minor allele frequency <1% and <0.01% for homozygous/hemizygous and heterozygous variants, respectively) in PID genes for which an association with increased susceptibility to bacterial infection was previously described.

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Results

176 children presenting with 185 sepsis episodes underwent WES, with a median age of 52 months (IQR 15.4–126.4), and a male/female ratio of 1.8. A total of 42 unique rare PID variants (2 homozygous, 7 hemizygous, and 33 heterozygous) were found in 44/176 (25%) patients. PIDs included all 8 PID categories as defined by the International Union of Immunological Societies. We did not observe a clinically significant correlation between clinical or laboratory characteristics of patients and the likelihood of finding a PID variant.

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Conclusions

Applying WES to a population-based cohort of previously healthy children with bacterial sepsis revealed mutations associated with PID in one out of four sepsis cases. WES represents a promising approach to investigate children with sepsis for underlying PID, which may have severe consequences if undiagnosed.

©2018The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies