Skip to main content
SpringerLink
Log in

HLA-G and IL-10 in serum in relation to HLA-G genotype and polymorphisms

  • Original Paper
  • Published:
Immunogenetics Aims and scope Submit manuscript

Abstract

The expression and importance of the non-classical human leukocyte antigen (HLA) class Ib gene, HLA-G, at the feto-maternal interface have been recognized. The HLA-G molecule is almost monomorphic and expressed in both membrane-bound and soluble isoforms. It has been shown to inhibit NK-mediated cell lysis and influence cytokine expression. Recently, a possible boarder immunoregulatory function of HLA-G also in adult life has been recognized. HLA-G gene polymorphism has been linked to differences in gene expression profile of alternatively spliced HLA-G transcripts and levels of specific HLA-G mRNA isoforms. On this background it is of general interest to further elucidate any associations between HLA-G polymorphism and protein expression. We have HLA-G genotyped 85 individuals attending IVF treatment, and further studied sHLA-G1/HLA-G5 and interleukin-10 (IL-10) in serum samples. In 21% of the serum samples sHLA-G1/HLA-G5 could be detected. There was no correlation between sHLA-G1/HLA-G5 and IL-10 concentrations in serum. Soluble HLA-G1/HLA-G5 was not detected in any samples homozygous for a 14-bp insertion polymorphism in exon 8 of the 3′-untranslated region (3′UTR) of the HLA-G gene (P=0.03; Fisher’s exact test). Polymorphisms in the 5′-upstream regulatory region (5′URR) of the HLA-G gene were also studied. In conclusion, this study indicates that polymorphisms in the 3′UTR and the 5′URR of the HLA-G gene may influence the expression of sHLA-G of possible importance in pathological pregnancies and also in organ transplantation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  • Contini P, Ghio M, Poggi A, Filaci G, Indiveri F, Ferrone S, Puppo F (2003) Soluble HLA-A,-B,-C and -G molecules induce apoptosis in T and NK CD8+ cells and inhibit cytotoxic T cell activity through CD8 ligation. Eur J Immunol 33:125–134

    Article  PubMed  Google Scholar 

  • Creput C, Durrbach A, Menier C, Guettier C, Samuel D, Dausset J, Charpentier B, Carosella ED, Rouas-Freiss N (2003) Human leukocyte antigen-G (HLA-G) expression in biliary epithelial cells is associated with allograft acceptance in liver-kidney transplantation. J Hepatol 39:587–594

    Article  PubMed  Google Scholar 

  • Emmer PM, Steegers EA, Kerstens HM, Bulten J, Nelen WL, Boer K, Joosten I (2002) Altered phenotype of HLA-G expressing trophoblast and decidual natural killer cells in pathological pregnancies. Hum Reprod 17:1072–1080

    Google Scholar 

  • Fainardi E, Rizzo R, Melchiorri L, Vaghi L, Castellazzi M, Marzola A, Govoni V, Paolino E, Tola MR, Granieri E, Baricordi OR (2003) Presence of detectable levels of soluble HLA-G molecules in CSF of relapsing-remitting multiple sclerosis: relationship with CSF soluble HLA-I and IL-10 concentrations and MRI findings. J Neuroimmunol 142:149–158

    Article  PubMed  Google Scholar 

  • Fournel S, Aguerre-Girr M, Huc X, Lenfant F, Alam A, Toubert A, Bensussan A, Le Bouteiller P (2000) Cutting edge: soluble HLA-G1 triggers CD95/CD95 ligand-mediated apoptosis in activated CD8+ cells by interacting with CD8. J Immunol 164:6100–6104

    CAS  PubMed  Google Scholar 

  • Fujii T, Ishitani A, Geraghty DE (1994) A soluble form of the HLA-G antigen is encoded by a messenger ribonucleic acid containing intron 4. J Immunol 153:5516–5524

    CAS  PubMed  Google Scholar 

  • Fuzzi B, Rizzo R, Criscuoli L, Noci I, Melchiorri L, Scarselli B, Bencini E, Menicucci A, Baricordi OR (2002) HLA-G expression in early embryos is a fundamental prerequisite for the obtainment of pregnancy. Eur J Immunol 32:311–315

    Article  CAS  PubMed  Google Scholar 

  • Goldman-Wohl DS, Ariel I, Greenfield C, Hochner-Celnikier D, Cross J, Fisher S, Yagel S (2000) Lack of human leukocyte antigen-G expression in extravillous trophoblasts is associated with pre-eclampsia. Mol Hum Reprod 6:88–95

    Article  CAS  PubMed  Google Scholar 

  • Hara N, Fujii T, Yamashita T, Kozuma S, Okai T, Taketani Y (1996) Altered expression of human leukocyte antigen G (HLA-G) on extravillous trophoblasts in preeclampsia: immunohistological demonstration with anti-HLA-G specific antibody “87G” and anti-cytokeratin antibody “CAM5.2”. Am J Reprod Immunol 36:349–358

    CAS  PubMed  Google Scholar 

  • Hunt JS, Jadhav L, Chu W, Geraghty DE, Ober C (2000) Soluble HLA-G circulates in maternal blood during pregnancy. Am J Obstet Gynecol 183:682–688

    Google Scholar 

  • Hviid TV, Møller C, Sørensen S, Morling N (1998) Co-dominant expression of the HLA-G gene and various forms of alternatively spliced HLA-G mRNA in human first trimester trophoblast. Hum Immunol 59:87–98

    Article  CAS  PubMed  Google Scholar 

  • Hviid TV, Sorensen S, Morling N (1999) Polymorphism in the regulatory region located more than 1.1 kilobases 5′ to the start site of transcription, the promoter region, and exon 1 of the HLA-G gene. Hum Immunol 60:1237–1244

    Article  CAS  PubMed  Google Scholar 

  • Hviid TV, Hylenius S, Hoegh AM, Kruse C, Christiansen OB (2002) HLA-G polymorphisms in couples with recurrent spontaneous abortions. Tissue Antigens 60:122–132

    Article  CAS  PubMed  Google Scholar 

  • Hviid TV, Hylenius S, Rorbye C, Nielsen LG (2003) HLA-G allelic variants are associated with differences in the HLA-G mRNA isoform profile and HLA-G mRNA levels. Immunogenetics 55:63–79

    PubMed  Google Scholar 

  • Jurisicova A, Casper RF, MacLusky NJ, Mills GB, Librach CL (1996) HLA-G expression during preimplantation human embryo development. Proc Natl Acad Sci USA 93:161–165

    Article  PubMed  Google Scholar 

  • Kanai T, Fujii T, Kozuma S, Yamashita T, Miki A, Kikuchi A, Taketani Y (2001) Soluble HLA-G influences the release of cytokines from allogeneic peripheral blood mononuclear cells in culture. Mol Hum Reprod 7:195–200

    CAS  PubMed  Google Scholar 

  • Kapasi K, Albert SE, Yie S, Zavazava N, Librach CL (2000) HLA-G has a concentration-dependent effect on the generation of an allo-CTL response. Immunology 101:191–200

    Article  CAS  PubMed  Google Scholar 

  • Kirszenbaum M, Moreau P, Gluckman E, Dausset J, Carosella E (1994) An alternatively spliced form of HLA-G mRNA in human trophoblasts and evidence for the presence of HLA-G transcript in adult lymphocytes. Proc Natl Acad Sci USA 91:4209–4213

    CAS  PubMed  Google Scholar 

  • Kovats S, Main EK, Librach C, Stubblebine M, Fisher SJ, DeMars R (1990) A class I antigen, HLA-G, expressed in human trophoblasts. Science 248:220–223

    CAS  PubMed  Google Scholar 

  • Le Bouteiller P, Blaschitz A (1999) The functionality of HLA-G is emerging. Immunol Rev 167:233–244

    PubMed  Google Scholar 

  • LeMaoult J, Le Discorde M, Rouas-Freiss N, Moreau P, Menier C, McCluskey J, Carosella ED (2003) Biology and functions of human leukocyte antigen-G in health and sickness. Tissue Antigens 62:273–284

    Article  PubMed  Google Scholar 

  • Lila N, Rouas-Freiss N, Dausset J, Carpentier A, Carosella ED (2001) Soluble HLA-G protein secreted by allo-specific CD4+ T cells suppresses the allo-proliferative response: a CD4+ T cell regulatory mechanism. Proc Natl Acad Sci USA 98:12150–12155

    CAS  PubMed  Google Scholar 

  • Lila N, Amrein C, Guillemain R, Chevalier P, Latremouille C, Fabiani JN, Dausset J, Carosella ED, Carpentier A (2002) Human leukocyte antigen-G expression after heart transplantation is associated with a reduced incidence of rejection. Circulation 105:1949–1954

    Article  PubMed  Google Scholar 

  • Lim KH, Zhou Y, Janatpour M, McMaster M, Bass K, Chun SH, Fisher SJ (1997) Human cytotrophoblast differentiation/invasion is abnormal in pre-eclampsia. Am J Pathol 151:1809–1818

    CAS  PubMed  Google Scholar 

  • Menier C, Saez B, Horejsi V, Martinozzi S, Krawice-Radanne I, Bruel S, Le Danff C, Reboul M, Hilgert I, Rabreau M, Larrad ML, Pla M, Carosella ED, Rouas-Freiss N (2003) Characterization of monoclonal antibodies recognizing HLA-G or HLA-E: new tools to analyze the expression of nonclassical HLA class I molecules. Hum Immunol 64:315–326

    Article  PubMed  Google Scholar 

  • Miller SA, Dykes DD, Polesky HF (1988) A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 16:1215

    PubMed  Google Scholar 

  • Moreau P, Adrian-Cabestre F, Menier C, Guiard V, Gourand L, Dausset J, Carosella ED, Paul P (1999) IL-10 selectively induces HLA-G expression in human trophoblasts and monocytes. Int Immunol 11:803–811

    CAS  PubMed  Google Scholar 

  • O’Brien M, McCarthy T, Jenkins D, Paul P, Dausset J, Carosella ED, Moreau P (2001) 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. Cell Mol Life Sci 58:1943–1949

    CAS  PubMed  Google Scholar 

  • Ober C, Aldrich CL, Chervoneva I, Billstrand C, Rahimov F, Gray HL, Hyslop T (2003) Variation in the HLA-G promoter region influences miscarriage rates. Am J Hum Genet 72:1425–1435

    Article  PubMed  Google Scholar 

  • Pfeiffer KA, Rebmann V, van der Ven K (2000) Soluble histocompatibility antigen levels in early pregnancy after IVF. Hum Immunol 61:559–564

    Article  CAS  PubMed  Google Scholar 

  • Pfeiffer KA, Fimmers R, Engels G, van der Ven, van der Ven (2001) The HLA-G genotype is potentially associated with idiopathic recurrent spontaneous abortion. Mol Hum Reprod 7:373–378

    Google Scholar 

  • Ponte M, Cantoni C, Biassoni R, Tradori-Cappai A, Bentivoglio G, Vitale C, Bertone S, Moretta A, Moretta L, Mingari MC (1999) Inhibitory receptors sensing HLA-G1 molecules in pregnancy: decidua-associated natural killer cells express LIR-1 and CD94/NKG2A and acquire p49, an HLA-G1-specific receptor. Proc Natl Acad Sci USA 96:5674–5679

    Article  CAS  PubMed  Google Scholar 

  • Rebmann V, Pfeiffer K, Passler M, Ferrone S, Maier S, Weiss E, Grosse-Wilde H (1999) Detection of soluble HLA-G molecules in plasma and amniotic fluid. Tissue Antigens 53:14–22

    Article  PubMed  Google Scholar 

  • Rebmann V, van der Ven K, Passler M, Pfeiffer K, Krebs D, Grosse-Wilde H (2001) Association of soluble HLA-G plasma levels with HLA-G alleles. Tissue Antigens 57:15–21

    Article  CAS  PubMed  Google Scholar 

  • Rebmann V, Busemann A, Lindemann M, Grosse-Wilde H (2003) Detection of HLA-G5 secreting cells. Hum Immunol 64:1017–1024

    Article  PubMed  Google Scholar 

  • Rieger L, Hofmeister V, Probe C, Dietl J, Weiss EH, Steck T, Kammerer U (2002) Th1- and Th2-like cytokine production by first trimester decidual large granular lymphocytes is influenced by HLA-G and HLA-E. Mol. Hum Reprod 8:255–261

    Article  Google Scholar 

  • Rouas-Freiss N, Goncalves RM, Menier C, Dausset J, Carosella ED (1997) Direct evidence to support the role of HLA-G in protecting the fetus from maternal uterine natural killer cytolysis. Proc Natl Acad Sci USA 94:11520–11525

    Article  PubMed  Google Scholar 

  • Rousseau P, Le Discorde M, Mouillot G, Marcou C, Carosella ED, Moreau P (2003) The 14-bp deletion-insertion polymorphism in the 3′ UT region of the HLA-G gene influences HLA-G mRNA stability. Hum Immunol 64:1005–1010

    Article  PubMed  Google Scholar 

  • Solier C, Aguerre-Girr M, Lenfant F, Campan A, Berrebi A, Rebmann V, Grosse-Wilde H, Le Bouteiller P (2002) Secretion of pro-apoptotic intron 4-retaining soluble HLA-G1 by human villous trophoblast. Eur J Immunol 32:3576–3586

    Article  PubMed  Google Scholar 

  • Steinborn A, Rebmann V, Scharf A, Sohn C, Grosse-Wilde H (2003) Placental abruption is associated with decreased maternal plasma levels of soluble HLA-G. J Clin Immunol 23:307–314

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

This study was supported by The Pharmacy Foundation of 1991, The Copenhagen Hospital Corporation, The A.P. Møller Foundation for the Advancement of Medical Science, The Plasmid Foundation and The Danish Medical Association Research Fund.

Author information

Authors and Affiliations

  1. Department of Clinical Biochemistry, Copenhagen University Hospital, Rigshospitalet, 9 Blegdamsvej, 2100, Copenhagen Ø, Denmark

    Thomas Vauvert F. Hviid

  2. Department of Experimental and Diagnostic Medicine, Section of Medical Genetics, University of Ferrara, Via Luigi Borsari 46, 44100, Ferrara, Italy

    Roberta Rizzo, Loredana Melchiorri & Olavio R. Baricordi

  3. Fertility Clinic 4071, The Juliane Marie Centre, Rigshospitalet, 9 Blegdamsvej, 2100, Copenhagen Ø, Denmark

    Ole B. Christiansen & Anette Lindhard

  4. Department of Experimental and Diagnostic Medicine, Biotechnology Center, University of Ferrara, Via Luigi Borsari 46, 44100, Ferrara, Italy

    Olavio R. Baricordi

Authors
  1. Thomas Vauvert F. Hviid
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Roberta Rizzo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ole B. Christiansen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Loredana Melchiorri
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Anette Lindhard
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Olavio R. Baricordi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Thomas Vauvert F. Hviid.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hviid, T.V.F., Rizzo, R., Christiansen, O.B. et al. HLA-G and IL-10 in serum in relation to HLA-G genotype and polymorphisms. Immunogenetics 56, 135–141 (2004). https://doi.org/10.1007/s00251-004-0673-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00251-004-0673-2

Keywords

Search

Navigation