Hiby, SE, Walker, JJ orcid.org/0000-0002-8922-083X, O'Shaughnessy, KM et al. (4 more authors) (2004) Combinations of Maternal KIR and Fetal HLA-C Genes Influence the Risk of Preeclampsia and Reproductive Success. Journal of Experimental Medicine, 200 (8). pp. 957-965. ISSN 0022-1007
Abstract
Preeclampsia is a serious complication of pregnancy in which the fetus receives an inadequate supply of blood due to failure of trophoblast invasion. There is evidence that the condition has an immunological basis. The only known polymorphic histocompatibility antigens on the fetal trophoblast are HLA-C molecules. We tested the idea that recognition of these molecules by killer immunoglobulin receptors (KIRs) on maternal decidual NK cells is a key factor in the development of preeclampsia. Striking differences were observed when these polymorphic ligand: receptor pairs were considered in combination. Mothers lacking most or all activating KIR (AA genotype) when the fetus possessed HLA-C belonging to the HLA-C2 group were at a greatly increased risk of preeclampsia. This was true even if the mother herself also had HLA-C2, indicating that neither nonself nor missing-self discrimination was operative. Thus, this interaction between maternal KIR and trophoblast appears not to have an immune function, but instead plays a physiological role related to placental development. Different human populations have a reciprocal relationship between AA frequency and HLA-C2 frequency, suggesting selection against this combination. In light of our findings, reproductive success may have been a factor in the evolution and maintenance of human HLA-C and KIR polymorphisms.
Metadata
Item Type: | Article |
---|---|
Authors/Creators: |
|
Copyright, Publisher and Additional Information: | © 2004 Rockefeller University Press. Reproduced in accordance with the publisher's self-archiving policy. |
Keywords: | natural killer cells; HLA; placenta; killer immunoglobulin receptors; trophoblast |
Dates: |
|
Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Inst of Biomed & Clin Sciences (LIBACS) (Leeds) > Obstetrics & Gynaecology (Leeds) |
Funding Information: | Funder Grant number British Heart Foundation UNIV OF CAMBRIDGE |
Depositing User: | Symplectic Publications |
Date Deposited: | 08 Sep 2017 14:48 |
Last Modified: | 08 Sep 2017 14:48 |
Status: | Published |
Publisher: | Rockefeller University Press |
Identification Number: | 10.1084/jem.20041214 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:117171 |