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dc.contributor.authorKernan, Kate F
dc.contributor.authorGhaloul-Gonzalez, Lina
dc.contributor.authorVockley, Jerry
dc.contributor.authorLamb, Janette
dc.contributor.authorHollingshead, Deborah
dc.contributor.authorChandran, Uma
dc.contributor.authorSethi, Rahil
dc.contributor.authorPark, Hyun-Jung
dc.contributor.authorBerg, Robert A
dc.contributor.authorWessel, David
dc.contributor.authorPollack, Murray M
dc.contributor.authorMeert, Kathleen L
dc.contributor.authorHall, Mark W
dc.contributor.authorNewth, Christopher J L
dc.contributor.authorLin, John C
dc.contributor.authorDoctor, Allan
dc.contributor.authorShanley, Tom
dc.contributor.authorCornell, Tim
dc.contributor.authorHarrison, Rick E
dc.contributor.authorZuppa, Athena F
dc.contributor.authorBanks, Russel
dc.contributor.authorReeder, Ron W
dc.contributor.authorHolubkov, Richard
dc.contributor.authorNotterman, Daniel A
dc.contributor.authorDean, J Michael
dc.contributor.authorCarcillo, Joseph A
dc.date.accessioned2022-01-19T16:41:22Z
dc.date.available2022-01-19T16:41:22Z
dc.date.issued2022-01-01
dc.identifier.urihttp://hdl.handle.net/10713/17633
dc.description.abstractPurpose: Our understanding of inborn errors of immunity is increasing; however, their contribution to pediatric sepsis is unknown. Methods: We used whole-exome sequencing (WES) to characterize variants in genes related to monogenic immunologic disorders in 330 children admitted to intensive care for severe sepsis. We defined candidate variants as rare variants classified as pathogenic or potentially pathogenic in QIAGEN’s Human Gene Mutation Database or novel null variants in a disease-consistent inheritance pattern. We investigated variant correlation with infection and inflammatory phenotype. Results: More than one in two children overall and three of four African American children had immunodeficiency-associated variants. Children with variants had increased odds of isolating a blood or urinary pathogen (blood: OR 2.82, 95% CI: 1.12–7.10, p = 0.023, urine: OR: 8.23, 95% CI: 1.06–64.11, p = 0.016) and demonstrating increased inflammation with hyperferritinemia (ferritin ≥ 500 ng/mL, OR: 2.16, 95% CI: 1.28–3.66, p = 0.004), lymphopenia (lymphocyte count < 1000/µL, OR: 1.66, 95% CI: 1.06 – 2.60, p = 0.027), thrombocytopenia (platelet count < 150,000/µL, OR: 1.76, 95% CI: 1.12–2.76, p = 0.013), and CRP greater than 10 mg/dl (OR: 1.71, 95% CI: 1.10–2.68, p = 0.017). They also had increased odds of requiring extracorporeal membrane oxygenation (ECMO, OR: 4.19, 95% CI: 1.21–14.5, p = 0.019). Conclusion: Herein, we describe the genetic findings in this severe pediatric sepsis cohort and their microbiologic and immunologic significance, providing evidence for the phenotypic effect of these variants and rationale for screening children with life-threatening infections for potential inborn errors of immunity. © 2021, The Author(s).en_US
dc.description.urihttps://doi.org/10.1007/s10875-021-01183-4en_US
dc.language.isoenen_US
dc.publisherSpringer Natureen_US
dc.relation.ispartofJournal of Clinical Immunologyen_US
dc.rights© 2021. The Author(s).en_US
dc.subjectHyperinflammationen_US
dc.subjectInborn errors of immunityen_US
dc.subjectPrimary immunodeficiencyen_US
dc.subjectSepsisen_US
dc.titlePrevalence of Pathogenic and Potentially Pathogenic Inborn Error of Immunity Associated Variants in Children with Severe Sepsis.en_US
dc.typeArticleen_US
dc.identifier.doi10.1007/s10875-021-01183-4
dc.identifier.pmid34973142
dc.source.journaltitleJournal of clinical immunology
dc.source.countryUnited States
dc.source.countryNetherlands


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