Stemcel biology/Regenerative medicine (incl. bloodtransfusion

Alegre

Ameres

Arck

Bracamonte-Baran

Burlingham

Cannon

Carosella

Chan

Chazara

Cheeran

Chen

Chou

Claas

Constantin

Cook

Crespo

de Vries

Djurisic

Dollard

Enders

Faridi

Fisher

Foley

Gomez-Lozano

Gong

Hardy

Harrison

Hiby

Huard

Hviid

Hylenius

Iyer

Kalpoe

Kenneson

Kharrazi

King

Korndewal

La Torre

Larsen

Le Bouteiller

Maloney

Mandelboim

Mazzarino

Moffett-King

Mold

Moreau

Nancy

Onno

O’Brien

O’Reilly

Pacasova

Parham

Pass

Pichler

Rizzo

Robinson

Rocha

Rouas-Freiss

Schipper

Schleiss

Sharkey

Smits

Steinborn

Stern

Strong

Taams

Tilburgs

Uhrberg

van Kampen

van Rood

van Rooijen

Wilkinson

Xiong

Yamamoto-Tabata

Zheng

Rovito, R.

Claas, F.H.J.

Haasnoot, G.W.

Roelen, D.L.

Kroes, A.C.M.

Eikmans, M.

Vossen, A.C.T.M.

Leiden University Scholary Publications

Congenital Cytomegalovirus Infection: Maternal-Child HLA-C, HLA-E, and HLA-G Affect Clinical Outcome

Roberta Rovito

Frans H. J. Claas

Geert W. Haasnoot

Dave L. Roelen

Aloys C. M. Kroes

Michael Eikmans

Ann C. T. M. Vossen

Crossref

Frontiers in Immunology

Congenital Cytomegalovirus Infection: Maternal–Child HLA-C, HLA-E, and HLA-G Affect Clinical Outcome

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

NARCIS 

Frontiers - Publisher Connector

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

Directory of Open Access Journals

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.Transplantation and autoimmunit

table_4.docx

http://dx.doi.org/10.3389/fimmu.2017.01904