title: T and B Cell Markers in Dried Blood Spots of Neonates with Congenital Cytomegalovirus Infection: B Cell Numbers at Birth Are Associated with Long-Term Outcomes.
abstract: Congenital CMV infection (cCMV) is the most common congenital infection that can cause long-term impairment (LTI). The pathogenesis of LTI is not completely understood. Fetal immunity may play a role in controlling the infection and preventing LTI, although immune activation may also contribute to fetal immunopathology. In this study, we analyzed various molecular markers of T and B cell numbers in neonatal dried blood spots of 99 children with cCMV and 54 children without cCMV: δRec-ψJα signal joints on TCR excision circles, intron recombination signal sequence k-deleting element signal joints on Igκ-deleting recombination excision circles, genomic intron recombination signal sequence k-deleting element coding joint, genomic Vδ1-Jδ1, and Vδ2-Jδ1 rearrangements. Of this cohort, clinical symptoms at birth and LTI at 6 y of age were recorded. Neonates with cCMV had fewer TCR excision circles in their blood than non-infected controls. Furthermore, cCMV infection was associated with increased numbers of γδ T cells and B cells, and these numbers were positively correlated with CMV viral load in the dried blood spots. Infected children with a better long-term outcome had higher numbers of B cells at birth than those who developed LTI; no difference in B cell replication was observed. The potential protective role of B cells in controlling cCMV-related disease and the clinical value of this marker as a predictor of long-term outcome merit further evaluation.
authors.affiliation: Department of Medical Microbiology, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands; R.Rovito@lumc.nl.
authors.forename: Roberta
authors.identifier: 0000-0002-8640-844X
authors.initials: R
authors.lastname: Rovito
authors.affiliation: Department of Medical Microbiology, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands.|Centre for Infectious Diseases, Epidemiology and Surveillance, National Institute of Public Health and the Environment, 3720 BA, Bilthoven, the Netherlands.
authors.forename: Marjolein J
authors.initials: MJ
authors.lastname: Korndewal
authors.affiliation: Department of Immunology and Pathology, Central Clinical School, Monash University, Melbourne, VIC 3800, Australia.
authors.forename: Menno C
authors.identifier: 0000-0003-4161-1919
authors.initials: MC
authors.lastname: van Zelm
authors.affiliation: Medical Statistics and Bioinformatics, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands; and.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Ziagkos
authors.affiliation: Department of Medical Microbiology, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands.
authors.forename: Els
authors.initials: E
authors.lastname: Wessels
authors.affiliation: Department of Immunology, Erasmus MC University Medical Centre Rotterdam, 3015 CN, Rotterdam, the Netherlands.
authors.forename: Mirjam
authors.identifier: 0000-0002-1510-3104
authors.initials: M
authors.lastname: van der Burg
authors.affiliation: Department of Medical Microbiology, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands.
authors.forename: Aloys C M
authors.initials: AC
authors.lastname: Kroes
authors.affiliation: Department of Immunology, Erasmus MC University Medical Centre Rotterdam, 3015 CN, Rotterdam, the Netherlands.
authors.forename: Anton W
authors.identifier: 0000-0002-2078-3220
authors.initials: AW
authors.lastname: Langerak
authors.affiliation: Department of Medical Microbiology, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands.
authors.forename: Ann C T M
authors.identifier: 0000-0003-1750-2843
authors.initials: AC
authors.lastname: Vossen
mesh_terms: D001402:B-Lymphocytes / Q000276:immunology*; D015415:Biomarkers; D002648:Child; D015331:Cohort Studies; D003586:Cytomegalovirus Infections / Q000150:complications / Q000151:congenital* / Q000276:immunology*; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D018655:Lymphocyte Count; D008297:Male; D060888:Real-Time Polymerase Chain Reaction; D012189:Retrospective Studies; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D015415:Biomarkers