Jean Dausset

Altered HLA-G transcription in pre-eclampsia is associated with allele specific inheritance: possible role of the HLA-G gene in susceptibility to the disease

Abstract: Pre-eclampsia is a disorder of human pregnancy occuring in 5-10 % of all births, and represents the leading cause of infant morbidity and mortality and maternal death. In pre-eclampsia, invasion of fetal trophoblasts into maternal arteries during early pregnancy is shallow or absent. Here we examined the hypothesis that HLA-G, a non-classical class I HLA expressed in cytotrophoblasts, may act as a key gene in pre-eclampsia. We analysed HLA-G at the level of transcription and genotyped a silent CAC-CAT polymorphism in exon 3 and a 14-bp insertion/deletion in the 3′ untranslated region. A deficit in levels of the HLA-G3 transcript was observed in mild pre-eclampsia compared to normal placentas. The distribution of HLA-G polymorphisms was different between normal and pre-eclampsia samples. A correlation between the alteration in transcription of the HLA-G gene and certain HLA-G genotypes was also observed. Thus we provide the first evidence for a possible role of HLA-G in genetic susceptibility to, and pathogenesis of pre-eclampsia.

Human leukocyte antigen-G (HLA-G) expression in biliary epithelial cells is associated with allograft acceptance in liver-kidney transplantation

BACKGROUND/AIMSnLiver allograft is known to protect simultaneously transplanted organs from acute rejection. We have reported that only 6% of combined liver-kidney recipients, versus 32.5% of kidney recipients, develop kidney graft acute rejection. Release of soluble human leukocyte antigen (HLA) molecules by the liver has been proposed as a possible tolerogenic mechanism involved in the better acceptance of double transplants. The HLA-G molecule is acknowledged to possess tolerogenic properties.nnnMETHODSnWe investigated the involvement of HLA-G in allogeneic transplant acceptance by analyzing its expression in kidney and liver biopsies of 40 combined transplanted patients.nnnRESULTSnWe demonstrate the presence of HLA-G in 14 out of 40 liver and five out of nine kidney transplants biopsies. HLA-G is expressed de novo by cells that are otherwise frequently susceptible target cells of acute rejection, i.e. liver biliary and renal tubular epithelial cells. We show a significant association between HLA-G expression in liver biliary epithelial cells and the absence of liver graft rejection. No acute or chronic rejection of the kidney graft was observed in patients in whom HLA-G was expressed in the liver graft.nnnCONCLUSIONSnHLA-G expression in the liver allograft is associated with a lower frequency of hepatic and renal acute rejection and may be involved in the acceptance of simultaneously transplanted organs.

Immunotolerant functions of HLA-G

Abstract. HLA-G is a nonclassical major histocompatibility complex class I molecule selectively expressed on cytotrophoblasts at the fetal-maternal interface, where it plays a role in materno-fetal tolerance. In contrast to classical HLA-A, -B and -C class I molecules, HLA-G is characterized by (i) a tissue-restricted distribution, (ii) a limited polymorphism and (iii) a transcription of spliced messenger RNAs encoding for at least four membrane-bound and two soluble HLA-G isoforms. Extensive studies over the past few years have identified HLA-G as a molecule involved in immune tolerance. In this review, attempts were made to summarize the current state of knowledge of the effects of HLA-G on both natural killer and T cell functions and their implications in materno-fetal tolerance and tumor immunosurveillance.

Human Leukocyte Antigen-G: Immunotolerant Major Histocompatibility Complex Molecule in Transplantation

Abstract. HLA-G is a nonclassical major histocompatibility complex class I molecule selectively expressed on cytotrophoblasts at the fetal–maternal interface, where it plays a role in maternofetal tolerance. In this review, attempts were made to summarize the current state of knowledge of the effects of HLA-G on both natural killer cell and T cell functions and their implications in transplantation.