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.