Kate Kernan, MD
Assistant Professor
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, United States
Disclosure information not submitted.
Lina Ghaloul-Gonzalez, MD
Assistant Professor
Children's Hospital of Pittsburgh, United States
Disclosure information not submitted.
Jerry Vockley, MD PhD
Professor
Children's Hospital of Pittsburgh, United States
Disclosure information not submitted.
Janette Lamb, PhD
Director Genomics Research Core
University of Pittsburgh, United States
Disclosure information not submitted.
Deborah Hollingshead
Assistant Director Genomics Research Core
University of Pittsburgh, United States
Disclosure information not submitted.
Joseph Carcillo, MD
Professor
Children's Hospital of Pittsburgh of UPMC, United States
Disclosure information not submitted.
Robert Berg, MD, MCCM (he/him/his)
Division Chief, Pediatric Critical Care Medicine
Children's Hospital of Philadelphia
Merion Station, Pennsylvania, United States
Disclosure information not submitted.
David Wessel, MD
Executive Vice President, Chief Medical Officer, Physician-In-Chief
Childrens National Health Systems, United States
Disclosure information not submitted.
Murray Pollack, MBA, MD, MCCM
M.D.
Childrens National Health Systems, United States
Disclosure information not submitted.
Kathleen Meert, MD, FCCM (she/her/hers)
Professor and Chairman of Pediatrics
Children's Hospital of Michigan
Detroit, Michigan, United States
Disclosure information not submitted.
Mark Hall, MD, FCCM
Chief Division Pediatric Critical Care Medicine
Nationwide Children's Hospital At Ohio State University
Columbus, Ohio, United States
Disclosure information not submitted.
Christopher Newth, MD, ChB
Professor
Children's Hospital of Los Angeles, United States
Disclosure information not submitted.
John Lin, MD
Program Director, PCCM Fellowship
Washington University School of Medicine
Saint Louis, MO
Disclosure information not submitted.
Allan Doctor, MD
Professor
University of Maryland School of Medicine, United States
Disclosure information not submitted.
Tom Shanley, MD
Professor
Ann and Robert H Lurie Childrens Hospital of Chicago, United States
Disclosure information not submitted.
Timothy Cornell, MD
Chambers-Okamura Endowed Professor of Pediatric Critical Care Medicine
Stanford University - Lucille Packard Children's Hosptal Stanford, United States
Disclosure information not submitted.
Rick Harrison, MD
Professor
Ronald Reagan UCLA Medical Center, United States
Disclosure information not submitted.
Collaborative Pediatric Critical Care Research Network, n/a
.
National Institute of Child Health and Human Development
Ethnicity, United States
Disclosure information not submitted.
Title: Pathogenic and Potentially Pathogenic Inborn Errors of Immunity in Children with Severe Sepsis
Introduction: Our understanding of the inborn errors of immunity that cause immunodeficiencies is increasing however, their contribution to pediatric sepsis is unknown.
Methods: We used whole exome sequencing to characterize variants previously reported in monogenic immunologic disorders in 330 children admitted to intensive care for severe sepsis. Candidate variants were restricted to novel null variants or rare variants classified as pathogenic or potentially pathogenic in Qiagen’s Human Genetic Mutation Database in a disease consistent inheritance pattern.
Results: More than one in two children overall and three of four African American children had immunodeficiency-associated variants. Children with candidate variants had increased odds of isolating a blood or urinary pathogen and had decreased odds of culture negative sepsis (blood: OR 2.82, 95% CI 1.12 – 7.10, p-value = 0.023, urine: OR: 8.23, 95% CI 1.05 – 64.11, p-value = 0.02, culture negative: OR 0.59, 95% CI 0.38 – 0.92). They also demonstrated laboratory evidence of increased immune activation with increased odds of hyperferritinemia (ferritin >500ng/ml, OR: 2.16, 95% CI: 1.28 – 3.66, p-value = 0.003), lymphopenia (minimum lymphocyte count < 1000/µL, OR: 1.66, 95% CI: 1.05 – 2.60, p-value = 0.027), thrombocytopenia (minimum platelet count < 150,000/µL, OR: 1.76, 95% CI: 1.12 – 2.76, p-value = 0.013), and CRP greater than 10mg/dl (OR: 1.71, 95% CI:1.10 – 2.68, p-value = 0.017).
Conclusion: Herein, we describe the genetic findings in this pediatric sepsis cohort and their microbiologic and immunologic significance providing rationale for screening children with life-threatening infection for potential inborn errors of immunity.