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

• Published in: The Journal of immunology (1950) 2017-01, Vol.198 (1), p.102-109
• Main Authors: Rovito, Roberta, Korndewal, Marjolein J, van Zelm, Menno C, Ziagkos, Dimitrios, Wessels, Els, van der Burg, Mirjam, Kroes, Aloys C M, Langerak, Anton W, Vossen, Ann C T M
• Format: Article
• Language: English
• Subjects: B-Lymphocytes - immunology; Biomarkers; Birth; Blood; Child; Children; Cohort Studies; Congenital infection; Cytomegalovirus; Cytomegalovirus Infections - complications; Cytomegalovirus Infections - congenital; Cytomegalovirus Infections - immunology; Female; Fetuses; Herpesviridae; Humans; Infant, Newborn; Infections; Lymphocyte Count; Lymphocytes; Lymphocytes B; Lymphocytes T; Male; Neonates; Real-Time Polymerase Chain Reaction; Recombination; Retrospective Studies; T cell receptors; T-Lymphocytes - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1601182

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.