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Mol. Hum. Reprod. Advance Access originally published online on December 5, 2005
Molecular Human Reproduction 2005 11(10):695-698; doi:10.1093/molehr/gah196
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© The Author 2005. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oupjournals.org

Editorial

Does ‘soluble’ HLA-G really exist? Another twist to the tale

I.L. Sargent

Nuffield Department of Obstetrics and Gynaecology, Oxford University, John Radcliffe Hospital, Headington, Oxford, UK

Abstract

HLA-G is thought to play a key role in implantation by modulating cytokine secretion to control trophoblast invasion and to maintain a local immunosuppressive state. It differs from other class I molecules in that the gene can be alternatively spliced to produce four membrane-bound (G1, G2, G3 and G4) and three soluble isoforms (G5, G6 and G7). The soluble isoforms have recently attracted attention as their levels may be diagnostic of poor trophoblast invasion in miscarriage or pre-eclampsia and the implantation potential of IVF embryos. Although the expression and function of HLA-G2, G3, G4 and G7 has previously been a matter of debate, until now it has been generally accepted that soluble HLA-G5 and HLA-G6 are both expressed and secreted by trophoblast. However, Blaschitz et al. (2005) have reinvestigated this question and come to the surprising conclusion that they are not. They have shown that trophoblast only expresses the membrane-bound HLA-G1 isoform and not soluble HLA-G5 and -G6. Furthermore, although soluble HLA-G could be found in trophoblast culture supernatants, it appears not to be derived by alternative splicing but by the cleavage of HLA-G1. The source of the soluble HLA-G may not matter from a diagnostic perspective, but these findings, if confirmed, have important implications for our understanding of the biology of HLA-G.


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A. van der Meer, H.G.M. Lukassen, B. van Cranenbroek, E.H. Weiss, D.D.M. Braat, M.J. van Lierop, and I. Joosten
Soluble HLA-G promotes Th1-type cytokine production by cytokine-activated uterine and peripheral natural killer cells
Mol. Hum. Reprod., February 1, 2007; 13(2): 123 - 133.
[Abstract] [Full Text] [PDF]


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