Abstract
HLA-G molecules are HLA class Ib antigens characterized by tolerogenic and immunoinhibitory functions. The HLA-G 14-bp insertion/deletion (ins/del) polymorphism controls protein expression and seems to be implicated in both MTX treatment response and SCT outcome. The aim of our study is to evaluate the role of HLA-G 14 bp polymorphism in subjects affected by hematological malignancies undergoing allo-SCT and receiving MTX therapy for GvHD prophylaxis. We performed a retrospective analysis of HLA-G 14 bp polymorphism using a specific PCR in 47 recipients and in their respective donors, and evaluated the correlation with the incidence of aGvHD, OS and disease-free survival (DFS) after allo-SCT. We did not observe any correlation between this polymorphism and the risk of aGvHD occurrence. On the contrary, we found that the recipients with a 14 bp ins/14 bp ins genotype were characterized by a lower OS and DFS in univariate and multivariate analysis (OS=OR: 3.235; DFS=OR: 3.302). These data indicate a role for recipient HLA-G 14 bp polymorphism in allo-SCT immunotolerance status and follow-up.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Rebmann V, Busemann A, Lindemann M, Grosse-Wilde H . Detection of HLA-G5 secreting cells. Hum Immunol 2003; 64: 1017–1024.
Kovats S, Main EK, Librach C, Stubblebine M, Fischer SJ, DeMars R . A class I antigen, HLA-G, expressed in human trophoblasts. Science 1990; 248: 220–223.
LeRond S, Le Maoult J, Creput C, Menier C, Deschamps M, Le Friec G et al. Alloareactive CD4+ and CD8+ T cells express the immunotolerant HLA-G molecule in mixed lymphocyte reactions: in vivo implications in transplanted patients. Eur J Immunol 2004; 34: 649–660.
Le Maux A, Noel G, Birebent B, Grosset JM, Vu N, De Giubert S et al. Soluble human leucocyte antigen- G molecules in peripheral blood haematopoietic stem cell transplantation: a specific role to prevent acute graft-versus-host disease and a link with regulatory T cells. Clin Exp Immunol 2008; 152: 50–56.
Carosella ED, Moreau P, Aractingi S, Rouas-Freiss N . HLA-G: a shield against inflammatory aggression. Trends Immunol 2001; 22: 553–555.
Megret F, Prehaud C, Lafage M, Moreau P, Rouas-Freiss N, Carosella ED et al. Modulation of HLA-G and HLA-E expression in human neuronal cells after rabies virus or herpes virus simplex type I infections. Hum Immunol 2007; 68: 294–302.
Rouas-Freiss N, Moreau P, Menier C, LeMoult J, Carosella ED . Expression of tolerogenic HLA-G molecules in cancer prevents antitumor responses. Semin Cancer Biol 2007; 17: 413–421.
Pistoia V, Morandi F, Wang X, Ferrone S . Soluble HLA-G: are they clinically relevant? Semin Cancer Biol 2007; 17: 469–479.
Qiu J, Terasaki PI, Miller J, Mizutani K, Cai J, Carosella ED . Soluble HLA-G expression and renal graft acceptance. Am J Transplant. 2006; 6: 2152–2156.
Luque J, Torres MI, Aumente MD, Marín J, García-Jurado G, González R et al. Soluble HLA-G in heart transplantation: their relationship to rejection episodes and immunosuppressive therapy. Hum Immunol 2006; 67: 257–263.
Lila N, Amrein C, Guillemain R, Chevalier P, Latmouille C, Fabiani JN et al. Human leucocyte antigen-G expression after heart transplantation is associated with a reduced incidence of rejection. Circulation 2002; 105: 1949–1954.
Crispim JC, Duarte RA, Soares CP, Costa R, Silva JS, Mendes-Junior CT . Human leucocyte antigen-G expression after kidney transplantation is associated with a reduced incidence of rejection. Transpl Immunol 2008; 18: 361–367.
Rousseau P, Le Discorde M, Mouillot G, Marcou C, Carosella ED, Moreau P . The 14 bp deletion- insertion polymorphism in the 3′ UT region of the HLA-G gene influences HLA-G mRNA stability. Hum Immunol 2003; 64: 1005–1010.
Hviid TV, Hylenius S, Rorbye C, Nielsen LG . HLA-G allelic variants are associated with differences in the HLA-G mRNA isoform profile and HLA-G mRNA levels. Immunogenetics 2003; 55: 63–79.
Hviid TV, Rizzo R, Christiansen OB, Melchiorri L, Lindhard A, Baricordi OR . HLA-G and IL-10 in plasma in relation to HLA-G genotype and polymorphisms. Immunogenetics 2004; 56: 135–141.
Rebmann V, van de Ven K, Passler M, Pfeiffer K, Krebs D, Grosse-Wilde H . Association of soluble HLA-G plasma levels with HLA-G alleles. Tissue Antigens 2001; 57: 15–21.
La Nasa G, Littera R, Locatelli F, Lai S, Alba F, Caocci G et al. The human leucocyte antigen-G 14-basepair polymorphism correlates with graft-versus-host disease in unrelated bone marrow transplantation for thalassaemia. Br J Haematol 2007; 139: 284–288.
Rizzo R, Rubini M, Govoni M, Padovan M, Melchiorri L, Stignani M et al. HLA-G 14-bp polymorphism regulates the methotrexate response in rheumatoid arthritis. Pharmacogenet Genomics 2006; 16: 615–623.
Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J et al. 1994 Consensus Conference on acute GVHD grading. Bone Marrow Transplant 1995; 15: 825–828.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
The authors declare no conflict of interest.
Rights and permissions
About this article
Cite this article
Chiusolo, P., Bellesi, S., Piccirillo, N. et al. The role of HLA–G 14-bp polymorphism in allo-HSCT after short-term course MTX for GvHD prophylaxis. Bone Marrow Transplant 47, 120–124 (2012). https://doi.org/10.1038/bmt.2011.40
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/bmt.2011.40
Keywords
This article is cited by
-
Immunomodulating functions of human leukocyte antigen-G and its role in graft-versus-host disease after allogeneic hematopoietic stem cell transplantation
Annals of Hematology (2021)
-
Infusion of Mesenchymal Stem Cells to Treat Graft Versus Host Disease: the Role of HLA-G and the Impact of its Polymorphisms
Stem Cell Reviews and Reports (2020)
-
Elevated soluble human leukocyte antigen G levels in patients after allogeneic stem cell transplantation are associated with less severe acute and chronic graft-versus-host disease
Bone Marrow Transplantation (2018)
-
Impact of HLA-G polymorphism on the outcome of allogeneic hematopoietic stem cell transplantation for metastatic renal cell carcinoma
Bone Marrow Transplantation (2018)
-
AAV vector-meditated expression of HLA-G reduces injury-induced corneal vascularization, immune cell infiltration, and fibrosis
Scientific Reports (2017)