Biology of Blood and Marrow Transplantation
Volume 15, Issue 11 , Pages 1366-1375 , November 2009

Donor KIR3DL1/3DS1 Gene and Recipient Bw4 KIR Ligand as Prognostic Markers for Outcome in Unrelated Hematopoietic Stem Cell Transplantation

  • Katia Gagne

      Affiliations

    • Etablissement Français du Sang, Université de Nantes, Nantes Atlantique Universités, “Immunovirologie et Polymorphisme génétique,” EA4271, Nantes, France
    • Laboratoire HLA, EFS Nantes, France
    • Corresponding Author InformationCorrespondence and reprint requests: Katia Gagne, PhD, EFS Pays de la Loire, EA4271 “Immunovirologie et Polymorphisme Génétique,” 34 boulevard Jean Monnet, 44011 Nantes cedex, France.
    • ,
  • Marc Busson

      Affiliations

    • Inserm UMRS 940, hôpital Saint-Louis, Paris, France
    • ,
  • Jean-Denis Bignon

      Affiliations

    • Etablissement Français du Sang, Université de Nantes, Nantes Atlantique Universités, “Immunovirologie et Polymorphisme génétique,” EA4271, Nantes, France
    • Laboratoire HLA, EFS Nantes, France
    • ,
  • Marie-Lorraine Balère-Appert

      Affiliations

    • France Greffe de Moelle, Agence de la Biomédecine, Saint-Denis La Plaine, France
    • ,
  • Pascale Loiseau

      Affiliations

    • Laboratoire d'Immunologie, hôpital Saint-Louis, AP-HP, Paris, France
    • ,
  • Anne Dormoy

      Affiliations

    • Laboratoire HLA, EFS Strasbourg, France
    • ,
  • Valérie Dubois

      Affiliations

    • Laboratoire HLA, EFS Lyon, France
    • ,
  • Pascale Perrier

      Affiliations

    • CHU, Nancy, France
    • ,
  • Isabelle Jollet

      Affiliations

    • Laboratoire HLA, EFS Poitiers, France
    • ,
  • Monique Bois

      Affiliations

    • Laboratoire HLA, EFS Poitiers, France
    • ,
  • Dominique Masson

      Affiliations

    • Laboratoire HLA, EFS Grenoble, France
    • ,
  • Agnès Moine

      Affiliations

    • Laboratoire HLA, EFS Grenoble, France
    • ,
  • Léna Absi

      Affiliations

    • Laboratoire HLA, EFS Saint-Etienne, France
    • ,
  • Didier Blaise

      Affiliations

    • SFGM-TC, Marseille, France
    • ,
  • Dominique Charron

      Affiliations

    • Inserm UMRS 940, hôpital Saint-Louis, Paris, France
    • Laboratoire d'Immunologie, hôpital Saint-Louis, AP-HP, Paris, France
    • ,
  • Colette Raffoux

      Affiliations

    • France Greffe de Moelle, Agence de la Biomédecine, Saint-Denis La Plaine, France
    • ,
  • ARS2000 FRM and FGM group

Received 16 February 2009 ,Accepted 25 June 2009.

References 

  1. Hansen JA, Petersdorf EW, Lin MT, et al. Genetics of allogeneic hematopoietic cell transplantation. Role of HLA matching, functional variation in immune response genes. Immunol Res. 2008;41:56–78
  2. Barrett AJ. Understanding and harnessing the graft-versus-leukaemia effect. Br J Haematol. 2008;142:877–888
  3. Ruggeri L, Capanni M, Urbani E, et al. Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants. Science. 2002;295:2097–2100
  4. Vivier E, Tomasello E, Baratin M, Walzer T, Ugolini S. Functions of natural killer cells. Nat Immunol. 2008;9:503–510
  5. Parham PMHC. class I molecules and KIRs in human history, health and survival. Nat Rev Immunol. 2005;5:201–214
  6. Stern M, Ruggeri L, Capanni M, Mancusi A, Velardi A. Human leukocyte antigens A23, A24, and A32 but not A25 are ligands for KIR3DL1. Blood. 2008;112:708–710
  7. Stewart CA, Laugier-Anfossi F, Vely F, et al. Recognition of peptide-MHC class I complexes by activating killer immunoglobulin-like receptors. Proc Natl Acad Sci USA. 2005;102:13224–13229
  8. Chewning JH, Gudme CN, Hsu KC, Selvakumar A, Dupont B. KIR2DS1-positive NK cells mediate alloresponse against the C2 HLA-KIR ligand group in vitro. J Immunol. 2007;179:854–868
  9. Morvan M, David G, Sebille V, et al. HLA KIR ligand environments and activating KIR control KIR NK-cell functions. Eur J Immunol. 2008;38:3474–3486
  10. O'Connor GM, Guinan KJ, Cunningham RT, Middleton D, Parham P, Gardiner CM. Functional polymorphism of the KIR3DL1/S1 receptor on human NK cells. J Immunol. 2007;178:235–241
  11. Gillespie GM, Bashirova A, Dong T, McVicar DW, Rowland-Jones SL, Carrington M. Lack of KIR3DS1 binding to MHC class I Bw4 tetramers in complex with CD8 + T cell epitopes. AIDS Res Hum Retroviruses. 2007;23:451–455
  12. Middleton D, Williams F, Halfpenny IA. KIR genes. Transpl Immunol. 2005;14:135–142
  13. Single RM, Martin MP, Meyer D, Gao X, Carrington M. Methods for assessing gene content diversity of KIR with examples from a global set of populations. Immunogenetics. 2008;60:711–725
  14. Uhrberg M, Valiante NM, Shum BP, et al. Human diversity in killer cell inhibitory receptor genes. Immunity. 1997;7:753–763
  15. Robinson J, Waller MJ, Fail SC, Marsh SG. The IMGT/HLA and IPD databases. Hum Mutat. 2006;27:1192–1199
  16. Ruggeri L, Mancusi A, Burchielli E, et al. NK cell alloreactivity and allogeneic hematopoietic stem cell transplantation. Blood Cells Mol Dis. 2008;40:84–90
  17. Willemze R, Rodrigues CA, Labopin M, et al. KIR-ligand incompatibility in the graft-versus-host direction improves outcomes after umbilical cord blood transplantation for acute leukemia. Leukemia. 2009;23:492–500
  18. Bignon JD, Gagne K. KIR matching in hematopoietic stem cell transplantation. Curr Opin Immunol. 2005;17:553–559
  19. Witt CS, Christiansen FT. The relevance of natural killer cell human leucocyte antigen epitopes and killer cell immunoglobulin-like receptors in bone marrow transplantation. Vox Sang. 2006;90:10–20
  20. Hsu KC, Keever-Taylor CA, Wilton A, et al. Improved outcome in HLA-identical sibling hematopoietic stem-cell transplantation for acute myelogenous leukemia predicted by KIR and HLA genotypes. Blood. 2005;105:4878–4884
  21. Gagne K, Brizard G, Gueglio B, et al. Relevance of KIR gene polymorphisms in bone marrow transplantation outcome. Hum Immunol. 2002;63:271–280
  22. Leung W, Iyengar R, Turner V, et al. Determinants of antileukemia effects of allogeneic NK cells. J Immunol. 2004;172:644–650
  23. Shilling HG, Young N, Guethlein LA, et al. Genetic control of human NK cell repertoire. J Immunol. 2002;169:239–247
  24. Yokoyama WM, Kim S. Licensing of natural killer cells by self-major histocompatibility complex class I. Immunol Rev. 2006;214:143–154
  25. Yawata M, Yawata N, Draghi M, Partheniou F, Little AM, Parham P. MHC class I-specific inhibitory receptors and their ligands structure diverse human NK-cell repertoires toward a balance of missing self-response. Blood. 2008;112:2369–2380
  26. Kim S, Sunwoo JB, Yang L, et al. HLA alleles determine differences in human natural killer cell responsiveness and potency. Proc Natl Acad Sci USA. 2008;105:3053–3058
  27. Gagne K, Busson M, Balere-Appert ML, et al. Relevance of KIR gene matching in unrelated hematopoietic stem cell transplantations. Tissue Antigens. 2007;69(Suppl 1):118–122
  28. Glucksberg H, Storb R, Fefer A, et al. Clinical manifestations of graft-versus-host disease in human recipients of marrow from HLA-matched sibling donors. Transplantation. 1974;18:295–304
  29. Przepiorka D, Weisdorf D, Martin P, et al. 1994 Consensus Conference on Acute GVHD Grading. Bone Marrow Transplant. 1995;15:825–828
  30. Loiseau P, Busson M, Balere ML, et al. HLA Association with hematopoietic stem cell transplantation outcome: the number of mismatches at HLA-A, -B, -C, -DRB1, or -DQB1 is strongly associated with overall survival. Biol Blood Marrow Transplant. 2007;13:965–974
  31. Fine JP, Gray RJ. A proportional hazards model for the sub distribution of a competing risk. JASA. 1999;94:496
  32. Cox DR. Regression models and life tables (with discussion). J R Stat Soc. 1972;34:187–220
  33. Cook MA, Milligan DW, Fegan CD, et al. The impact of donor KIR and patient HLA-C genotypes on outcome following HLA-identical sibling hematopoietic stem cell transplantation for myeloid leukemia. Blood. 2004;103:1521–1526
  34. Miller JS, Cooley S, Parham P, et al. Missing KIR ligands are associated with less relapse and increased graft-versus-host disease (GVHD) following unrelated donor allogeneic HCT. Blood. 2007;109:5058–5061
  35. Sun JY, Gaidulis L, Dagis A, et al. Killer Ig-like receptor (KIR) compatibility plays a role in the prevalence of acute GVHD in unrelated hematopoietic cell transplants for AML. Bone Marrow Transplant. 2005;36:525–530
  36. De Santis D, Bishara A, Witt CS, et al. Natural killer cell HLA-C epitopes and killer cell immunoglobulin-like receptors both influence outcome of mismatched unrelated donor bone marrow transplants. Tissue Antigens. 2005;65:519–528
  37. Kroger N, Binder T, Zabelina T, et al. Low number of donor activating killer immunoglobulin-like receptors (KIR) genes but not KIR-ligand mismatch prevents relapse and improves disease-free survival in leukemia patients after in vivo T-cell depleted unrelated stem cell transplantation. Transplantation. 2006;82:1024–1030
  38. Giebel S, Locatelli F, Lamparelli T, et al. Survival advantage with KIR ligand incompatibility in hematopoietic stem cell transplantation from unrelated donors. Blood. 2003;102:814–819
  39. Yabe T, Matsuo K, Hirayasu K, et al. Donor killer immunoglobulin-like receptor (KIR) genotype-patient cognate KIR ligand combination and antithymocyte globulin preadministration are critical factors in outcome of HLA-C-KIR ligand-mismatched T cell-replete unrelated bone marrow transplantation. Biol Blood Marrow Transplant. 2008;14:75–87
  40. Schellekens J, Rozemuller EH, Petersen EJ, van den Tweel JG, Verdonck LF, Tilanus MG. Patients benefit from the addition of KIR repertoire data to the donor selection procedure for unrelated haematopoietic stem cell transplantation. Mol Immunol. 2008;45:981–989
  41. Kim SY, Choi HB, Yoon HY, et al. Influence of killer cell immunoglobulin-like receptor genotypes on acute graft-vs-host disease after unrelated hematopoietic stem cell transplantation in Koreans. Tissue Antigens. 2007;69(Suppl 1):114–117
  42. Cooley S, Trachtenberg E, Bergemann TL, et al. Donors with group B KIR haplotypes improve relapse-free survival after unrelated hematopoietic cell transplantation for acute myelogenous leukemia. Blood. 2009;113:726–732
  43. La Nasa G, Littera R, Locatelli F, et al. Status of donor-recipient HLA class I ligands and not the KIR genotype is predictive for the outcome of unrelated hematopoietic stem cell transplantation in beta-thalassemia patients. Biol Blood Marrow Transplant. 2007;13:1358–1368
  44. Ludajic K, Balavarca Y, Bickeboller H, et al. KIR genes and KIR ligands affect occurrence of acute GVHD after unrelated, 12/12 HLA matched, hematopoietic stem cell transplantation. Bone Marrow Transplant. 2009;44:97–103
  45. Foley BA, De Santis D, Van Beelen E, Lathbury LJ, Christiansen FT, Witt CS. The reactivity of Bw4 + HLA-B and HLA-A alleles with KIR3DL1: implications for patient and donor suitability for haploidentical stem cell transplantations. Blood. 2008;112:435–443
  46. Gardiner CM, Guethlein LA, Shilling HG, et al. Different NK cell surface phenotypes defined by the DX9 antibody are due to KIR3DL1 gene polymorphism. J Immunol. 2001;166:2992–3001
  47. Carr WH, Pando MJ, Parham P. KIR3DL1 polymorphisms that affect NK cell inhibition by HLA-Bw4 ligand. J Immunol. 2005;175:5222–5229
  48. Morvan M, Willem C, Gagne K, et al. Phenotypic and functional analyses of KIR3DL1+ and KIR3DS1 + NK cell subsets demonstrate differential regulation by Bw4 molecules and induced KIR3DS1 expression on stimulated NK cells. J Immunol. 2009;182:6727–6735

 The first 2 authors contributed equally to this work.Financial disclosure: See Acknowledgments on page 1374.

PII: S1083-8791(09)00301-2

doi: 10.1016/j.bbmt.2009.06.015

Biology of Blood and Marrow Transplantation
Volume 15, Issue 11 , Pages 1366-1375 , November 2009

Article Tools

* Image Usage & Resolution