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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

Roberta Rovito, Marjolein J. Korndewal, Menno C. van Zelm, Dimitrios Ziagkos, Els Wessels, Mirjam van der Burg, Aloys C. M. Kroes, Anton W. Langerak and Ann C. T. M. Vossen
J Immunol January 1, 2017, 198 (1) 102-109; DOI: https://doi.org/10.4049/jimmunol.1601182
Roberta Rovito
*Department of Medical Microbiology, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands;
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Marjolein J. Korndewal
*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;
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Menno C. van Zelm
‡Department of Immunology and Pathology, Central Clinical School, Monash University, Melbourne, VIC 3800, Australia;
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Dimitrios Ziagkos
§Medical Statistics and Bioinformatics, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands; and
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Els Wessels
*Department of Medical Microbiology, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands;
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Mirjam van der Burg
¶Department of Immunology, Erasmus MC University Medical Centre Rotterdam, 3015 CN, Rotterdam, the Netherlands
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Aloys C. M. Kroes
*Department of Medical Microbiology, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands;
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Anton W. Langerak
¶Department of Immunology, Erasmus MC University Medical Centre Rotterdam, 3015 CN, Rotterdam, the Netherlands
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Ann C. T. M. Vossen
*Department of Medical Microbiology, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands;
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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.

Footnotes

  • This work was supported by European Union Seventh Framework Programme FP7/2012–2016 under grant agreement number 316655 (VACTRAIN).

  • The online version of this article contains supplemental material.

  • Abbreviations used in this article:

    cCMV
    congenital CMV infection
    cCMV+
    children with cCMV
    cCMV−
    children without cCMV
    cj intronRSS-Kde
    intron recombination signal sequence k-deleting element coding joint
    DBS
    dried blood spot
    intronRSS-Kde
    intron recombination signal sequence k-deleting element
    KREC
    Igκ-deleting recombination excision circle
    LTI
    long-term impairment
    PhHV
    phocine herpes virus
    TREC
    TCR excision circle.

  • Received July 6, 2016.
  • Accepted October 25, 2016.
  • Copyright © 2016 by The American Association of Immunologists, Inc.
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The Journal of Immunology: 198 (1)
The Journal of Immunology
Vol. 198, Issue 1
1 Jan 2017
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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
Roberta Rovito, Marjolein J. Korndewal, Menno C. van Zelm, Dimitrios Ziagkos, Els Wessels, Mirjam van der Burg, Aloys C. M. Kroes, Anton W. Langerak, Ann C. T. M. Vossen
The Journal of Immunology January 1, 2017, 198 (1) 102-109; DOI: 10.4049/jimmunol.1601182

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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
Roberta Rovito, Marjolein J. Korndewal, Menno C. van Zelm, Dimitrios Ziagkos, Els Wessels, Mirjam van der Burg, Aloys C. M. Kroes, Anton W. Langerak, Ann C. T. M. Vossen
The Journal of Immunology January 1, 2017, 198 (1) 102-109; DOI: 10.4049/jimmunol.1601182
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