Bibliographic Details
| Title: |
Congenital Cytomegalovirus Infection: Maternal–Child HLA-C, HLA-E, and HLA-G Affect Clinical Outcome |
| Authors: |
Roberta Rovito, Frans H. J. Claas, Geert W. Haasnoot, Dave L. Roelen, Aloys C. M. Kroes, Michael Eikmans, Ann C. T. M. Vossen |
| Source: |
Frontiers in Immunology, Vol 8 (2018) |
| Publisher Information: |
Frontiers Media S.A., 2018. |
| Publication Year: |
2018 |
| Collection: |
LCC:Immunologic diseases. Allergy |
| Subject Terms: |
mother–child HLA, congenital CMV infection, immunopathology, allo-reactivity, suboptimal viral clearance, NIMA effect, Immunologic diseases. Allergy, RC581-607 |
| More Details: |
Congenital CMV infection (cCMV) is the most common congenital infection causing permanent long-term impairments (LTI). cCMV immunopathogenesis is largely unknown due to the complex interplay between viral, maternal, placental, and child factors. In this study, a large retrospective nationwide cohort of children with cCMV and their mothers was used. HLA-C, HLA-E, and HLA-G were assessed in 96 mother–child pairs in relation to symptoms at birth and LTI at 6 years of age. The mothers were additionally typed for killer cell immunoglobulin-like receptors. The maternal HLA-G 14 bp deletion/deletion polymorphism was associated with a worse outcome, as the immunomodulation effect of higher protein levels may induce less CMV control, with a direct impact on placenta and fetus. The absence of maternal HLA-C belonging to the C2 group was associated with symptoms at birth, as activating signals on decidual NK may override inhibitory signals, contributing to a placental pro-inflammatory environment. Here, the increased HLA-E*0101 and HLA-C mismatches, which were associated with symptoms at birth, may enhance maternal allo-reactivity to fetal Ags, and cause suboptimal viral clearance. Finally, HLA-C non-inherited maternal antigens (NIMAs) were associated with LTI. The tolerance induced in the fetus toward NIMAs may indirectly induce a suboptimal CMV antiviral response throughout childhood. In light of our findings, the potential role of maternal–child HLA in controlling CMV infection and cCMV-related disease, and the clinical value as predictor for long-term outcome certainly deserve further evaluation. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
1664-3224 |
| Relation: |
http://journal.frontiersin.org/article/10.3389/fimmu.2017.01904/full; https://doaj.org/toc/1664-3224 |
| DOI: |
10.3389/fimmu.2017.01904 |
| Access URL: |
https://doaj.org/article/aadb88b92e3342fa94e3e9af29775dd9 |
| Accession Number: |
edsdoj.b88b92e3342fa94e3e9af29775dd9 |
| Database: |
Directory of Open Access Journals |
