Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Histocompatibility and Donor Selection Issues

UGT2B17 minor histocompatibility mismatch and clinical outcome after HLA-identical sibling donor stem cell transplantation

Bone Marrow Transplantation volume 51, pages 79–82 (2016)Cite this article

Subjects

Abstract

Minor histocompatibility Ags (mHags) have been implicated in the pathogenesis of GVHD after allogeneic hematopoietic stem cell transplantation (HSCT). Uridine diphospho-glucuronosyltransferase 2B17 (UGT2B17) gene deletion may act as a mHag and its association with acute GVHD (aGVHD) has been described. We retrospectively studied the clinical impact of a UGT2B17 mismatch in a cohort of 1127 patients receiving a HSCT from an HLA-identical sibling donor. UGT2B17 mismatch was present in 69 cases (6.1%). Incidence of severe aGVHD was higher in the UGT2B17 mismatched pairs (22.7% vs 14.6%), but this difference was not statistically significant (P: 0.098). We did not detect differences in chronic GVHD, overall survival, relapse-free survival, transplant-related mortality or relapse. Nevertheless, when we analyzed only those patients receiving grafts from a male donor (616 cases), aGVHD was significantly higher in the UGT2B17 mismatched group (25.1% vs 12.8%; P: 0.005) and this association was confirmed by the multivariate analysis (P: 0.043; hazard ratio: 2.16, 95% confidence interval: 1.03–4.57). Overall survival was worse for patients mismatched for UGT2B17 (P: 0.005). We conclude that UGT2B17 mismatch has a negative clinical impact in allogeneic HSCT from HLA-identical sibling donors only when a male donor is used. These results should be confirmed by other studies.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1

Similar content being viewed by others

References

  1. Beaulieu M, Levesque E, Tchernof A, Beatty BG, Belanger A, Hum DW . Chromosomal localization, structure, and regulation of the UGT2B17 gene, encoding a C19 steroid metabolizing enzyme. DNA Cell Biol 1997; 16: 1143–1154.

    Article  CAS  Google Scholar 

  2. Hum DW, Belanger A, Levesque E, Barbier O, Beaulieu M, Albert C et al. Characterization of UDP-glucuronosyltransferases active on steroid hormones. J Steroid Biochem Molec Biol 1999; 69: 413–423.

    Article  CAS  Google Scholar 

  3. Gallagher CJ, Balliet RM, Sun D, Chen G, Lazarus P . Sex differences in UDP-glucuronosyltransferase 2B17 expression and activity. Drug Metab Dispos 2010; 38: 2204–2209.

    Article  CAS  Google Scholar 

  4. Wilson W 3rd, Pardo-Manuel de Villena F, Lyn-Cook BD, Chatterjee PK, Bell TA, Detwiler DA et al. Characterization of a common deletion polymorphism of the UGT2B17 gene linked to UGT2B15. Genomics 2004; 84: 707–714.

    Article  CAS  Google Scholar 

  5. Xue Y, Sun D, Daly A, Yang F, Zhou X, Zhao M et al. Adaptive evolution of UGT2B17 copy-number variation. Am J Hum Genet 2008; 83: 337–346.

    Article  CAS  Google Scholar 

  6. Jakobsson J, Ekstrom L, Inotsume N, Garle M, Lorentzon M, Ohlsson C et al. Large differences in testosterone excretion in Korean and Swedish men are strongly associated with a UDP-glucuronosyl transferase 2B17 polymorphism. J Clin Endocr Metab 2006; 91: 687–693.

    Article  CAS  Google Scholar 

  7. Murata M, Warren EH, Riddell SR . A human minor histocompatibility antigen resulting from differential expression due to a gene deletion. J Exp Med 2003; 197: 1279–1289.

    Article  CAS  Google Scholar 

  8. Terakura S, Murata M, Warren EH, Sette A, Sidney J, Naoe T et al. A single minor histocompatibility antigen encoded by UGT2B17 and presented by human leukocyte antigen-A*2902 and -B*4403. Transplantation 2007; 83: 1242–1248.

    Article  CAS  Google Scholar 

  9. Terakura S, Murata M, Nishida T, Emi N, Akatsuka Y, Riddell SR et al. A UGT2B17-positive donor is a risk factor for higher transplant-related mortality and lower survival after bone marrow transplantation. Br J Haematol 2005; 129: 221–228.

    Article  CAS  Google Scholar 

  10. McCarroll SA, Bradner JE, Turpeinen H, Volin L, Martin PJ, Chilewski SD et al. Donor-recipient mismatch for common gene deletion polymorphisms in graft-versus-host disease. Nat Genet 2009; 41: 1341–1344.

    Article  CAS  Google Scholar 

  11. Spierings E, Drabbels J, Hendriks M, Pool J, Spruyt-Gerritse M, Claas F et al. A uniform genomic minor histocompatibility antigen typing methodology and database designed to facilitate clinical applications. PLoS One 2006; 1: e42.

    Article  Google Scholar 

  12. Goulmy E . Human minor histocompatibility antigens: new concepts for marrow transplantation and adoptive immunotherapy. Immunol Rev 1997; 157: 125–140.

    Article  CAS  Google Scholar 

  13. Warren EH, Gavin M, Greenberg PD, Riddell SR . Minor histocompatibility antigens as targets for T-cell therapy after bone marrow transplantation. Curr Opin Hematol 1998; 5: 429–433.

    Article  CAS  Google Scholar 

  14. Jervis S, Collins P, Tate D, Foster L, Bowman V, Adhern C et al. Increased severity of acute graft versus host disease as a result of differential expression following a homozygous gene deletion. Int J Immunogenet 2013; 40: 116–119.

    Article  CAS  Google Scholar 

  15. Martínez-Bravo MJ, Calderón-Cabrera C, Márquez-Malaver FJ, Rodríguez N, Guijarro M, Espigado I et al. Mismatch on glutathione S-transferase T1 increases the risk of graft-versus-host disease and mortality after allogeneic stem cell transplantation. Biol Blood Marrow Transplant 2014; 20: 1356–1362.

    Article  Google Scholar 

  16. Spierings E, Kim YH, Hendriks M, Borst E, Sergeant R, Canossi A et al. Multicenter analyses demonstrate significant clinical effects of minor histocompatibility antigens on GvHD and GvL after HLA-matched related and unrelated hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2013; 19: 1244–1253.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work has been partially financed by grants PI11/01690 and PI14/01646 from the Instituto de Salud Carlos III, co-financed by FEDER (Fondo Europeo de desarrollo regional) and by grant MTV3/120210 from Fundació Marató TV3.

Author information

Authors and Affiliations

  1. Clinical Hematology Department, Institut Català d’Oncologia, IDIBGi, Girona, Spain

    N Santos, R Rodríguez-Romanos & D Gallardo

  2. Hematology Department, Hospital Morales Meseguer, Murcia, Spain

    J B Nieto

  3. Hematology Department, Hospital Gregorio Marañón, Madrid, Spain

    I Buño & E Buces

  4. Hematology Department, Hospital Universitario Central de Asturias, Oviedo, Spain

    C Vallejo

  5. Hematology Department, Hospital Carlos Haya, Málaga, Spain

    A Jiménez-Velasco

  6. Hematology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain

    S Brunet

  7. Hematology Department, Hospital Ramón y Cajal, Madrid, Spain

    J López-Jiménez

  8. Hematology Department, Hospital Universitario, Salamanca, Spain

    M González

  9. Institut Català d’Oncologia, Badalona, Spain

    C Ferrá

  10. Hematology Department, Hospital Son Espases, Palma de Mallorca, Spain

    A Sampol

  11. Hematology Department, Hospital La Princesa, Madrid, Spain

    R de la Cámara

  12. Hematology Department, Hospital Clínic, Barcelona, Spain

    C Martínez

Authors
  1. N Santos
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R Rodríguez-Romanos
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J B Nieto
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. I Buño
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. C Vallejo
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. A Jiménez-Velasco
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. S Brunet
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. E Buces
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. J López-Jiménez
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. M González
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. C Ferrá
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. A Sampol
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. R de la Cámara
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. C Martínez
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. D Gallardo
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

on behalf of the GvHD/Immunotherapy Working Party of the Spanish Group of Hematopoietic Transplant (GETH)

Corresponding author

Correspondence to D Gallardo.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Additional information

Supplementary Information accompanies this paper on Bone Marrow Transplantation website

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Santos, N., Rodríguez-Romanos, R., Nieto, J. et al. UGT2B17 minor histocompatibility mismatch and clinical outcome after HLA-identical sibling donor stem cell transplantation. Bone Marrow Transplant 51, 79–82 (2016). https://doi.org/10.1038/bmt.2015.207

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/bmt.2015.207

This article is cited by

Search

Advanced search

Quick links