KIR2DS4 and Its Variant KIR1D in KIR-AA Genotype Donors Showed Differential Survival Impact in Patients with Lymphoid Disease after HLA-Matched Unrelated Hematopoietic Stem Cell Transplantation

被引:0
作者
Gowdavally, Sowmya [1 ,2 ]
Tsamadou, Chrysanthi [1 ,2 ]
Platzbecker, Uwe [3 ]
Sala, Elisa [4 ]
Valerius, Thomas [5 ]
Klein, Stefan [6 ]
Kroeger, Nicolaus [7 ]
Wulf, Gerald [8 ]
Einsele, Hermann [9 ]
Thurner, Lorenz [10 ]
Schaefer-Eckart, Kerstin [11 ]
Freitag, Sebastian [12 ]
Casper, Jochen [13 ]
Duerholt, Mareike [14 ]
Kaufmann, Martin [15 ]
Hertenstein, Bernd [16 ]
Ringhoffer, Mark [17 ]
Schmeller, Sandra [18 ]
Neuchel, Christine [1 ,2 ]
Rode, Immanuel [1 ,2 ]
Amann, Elisa Maria [1 ,2 ]
Richter, Anita [1 ,2 ]
Schrezenmeier, Hubert [1 ,2 ]
Mytilineos, Joannis [18 ,19 ]
Fuerst, Daniel [1 ,2 ,20 ]
机构
[1] Univ Hosp Ulm, Inst Clin Transfus Med & Immunogenet Ulm, German Red Cross Blood Transfus Serv, D-89081 Ulm, Germany
[2] Univ Ulm, Inst Transfus Med, Ulm, Germany
[3] Univ Leipzig, Dept Hematol Oncol & Hemostaseol, Leipzig, Germany
[4] Univ Ulm, Dept Internal Med 3, Ulm, Germany
[5] Christian Albrechts Univ Kiel, Sect Stem Cell Transplantat & Immunotherapy, Dept Med 2, Kiel, Germany
[6] Univ Med Mannheim, Med Clin 3, Mannheim, Germany
[7] Univ Hosp Hamburg Eppendorf, Dept Stem Cell Transplantat, Hamburg, Germany
[8] Univ Med Goettingen, Hematol & Med Oncol, Gottingen, Germany
[9] Univ Hosp Wurzburg, Dept Internal Med 2, Wurzburg, Germany
[10] Univ klinikum Saarlandes, Dept Internal Med I, Homburg, Germany
[11] Nuremberg Hosp, Med Clin 5 Hematol Oncol, Nurnberg, Germany
[12] Rostock Univ, Dept Med 3, Hematol Oncol Palliat Care, Med Ctr, Rostock, Germany
[13] Univ Clin, Klinikum Oldenburg, Dept Hematol & Oncol, Oldenburg, Germany
[14] Evangel Clin Essen Werden, Hematol Oncol, Essen, Germany
[15] Robert Bosch Krankenhaus, Dept Internal Med Oncol & Hematol 2, Stuttgart, Germany
[16] Klinikum Bremen Mitte, Hematol Oncol, Bremen, Germany
[17] Stadt Klinikum Karlsruhe, Med Clin 3, Karlsruhe, Germany
[18] German Registry Stem Cell Transplantat, Ulm, Germany
[19] German Natl Bone Marrow Donor Registry, Zent Knochenmarkspender Register Deutschland, Ulm, Germany
[20] Inst Clin Transfus Med & Immunogenet Ulm, Dept Transplantat Immunol, Helmholtzstr 10, D-89081 Ulm, Germany
来源
TRANSPLANTATION AND CELLULAR THERAPY | 2023年 / 29卷 / 07期
关键词
KIR2DS4; KIR1D; Hematopoietic Stem Cell; tTransplantation; KIR alloreactivity; KIR-Receptor; RECEPTOR GENES; ACUTE GVHD; CLASSIFICATION; ALLOREACTIVITY; POLYMORPHISMS; EXPRESSION; HAPLOTYPES; SELECTION; LIGANDS; RELAPSE;
D O I
10.1016/j.jtct.2023.04.006
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Previous studies have illustrated associations between the presence of activating killer cell immunoglobulin-like receptor (KIR) genes and lower susceptibility to hematologic malignancies in humans. In addition, favorable hematopoietic stem cell transplantation (HSCT) outcomes have been reported in patients who received transplants from donors with KIR genotypes dominant for activating KIR receptors. However, the association of activating KIR genes on an allelic level with disease and their impact on HSCT outcome has been little investigated to date. To this end, we genotyped a large transplantation cohort for KIR 2 Ig domains and short cytoplasmic tail 4 (KIR2DS4) polymorphisms and investigated their association with disease. We next investigated the impact of KIR-AA genotype donor KIR2DS4 polymorphisms (AA/KIR2DS4 versus AA/ KIR 1 Ig domain [KIR1D]) on clinical outcomes of HSCT in myeloid versus lymphoid patient subgroups. Among 2810 transplantation donor-recipient pairs, 68.8% (n = 1934) were 10/10 HLA-matched and 31.2% (n = 876) were 9/10 HLA-matched. The distribution of KIR1D was equal in patients and donors (P = .205). Multivariate analysis in 10/10 HLA-matched patients with lymphoid disease showed improved HSCT outcomes when they received grafts from AA/KIR1D donors (overall survival: hazard ratio [HR], .62, P = .002; disease free survival: HR, .70, P = .011; graft-versus-host disease-free and relapse-free survival: HR, .67, P = .002; nonrelapse mortality: HR, .55, P < .001). This effect was not seen in either 9/10 HLAmatched patients with lymphoid disease or patients with myeloid disease. Our study indicates that the presence of KIR1D alleles is not associated with disease in patients, and, interestingly, using grafts from AA/ KIR1D donors translated into beneficial survival outcomes in 10/10 HLA-matched patients with lymphoid disease.
引用
收藏
页码:457e1 / 457e10
页数:10
相关论文
共 37 条
  • [1] Novel associations between activating killer-cell immunoglobulin-like receptor genes and childhood leukemia
    Almalte, Zaema
    Samarani, Suzanne
    Iannello, Alexandre
    Debbeche, Olfa
    Duval, Michel
    Infante-Rivard, Claire
    Amre, Devendra K.
    Sinnett, Daniel
    Ahmad, Ali
    [J]. BLOOD, 2011, 118 (05) : 1323 - 1328
  • [2] The impact of donor full-length KIR2DS4 in the development of acute and chronic GVHD after unrelated allogeneic HSCT
    An, Kang
    Li, Benshang
    Luo, Changying
    Wang, Jianmin
    Luo, Chengjuan
    Chen, Jing
    [J]. PEDIATRIC TRANSPLANTATION, 2020, 24 (06)
  • [3] The role of KIR genes and ligands in leukemia surveillance
    Babor, Florian
    Fischer, Johannes C.
    Uhrberg, Markus
    [J]. FRONTIERS IN IMMUNOLOGY, 2013, 4
  • [4] The impact of KIR2DS4 alleles and the expression of KIR in the development of acute GVHD after unrelated allogeneic hematopoietic SCT
    Bao, X. J.
    Hou, L. H.
    Sun, A. N.
    Qiu, Q. C.
    Yuan, X. N.
    Chen, M. H.
    Chen, Z. X.
    He, J.
    [J]. BONE MARROW TRANSPLANTATION, 2010, 45 (09) : 1435 - 1441
  • [5] Structure/function of human killer cell immunoglobulin-like receptors: lessons from polymorphisms, evolution, crystal structures and mutations
    Campbell, Kerry S.
    Purdy, Amanda K.
    [J]. IMMUNOLOGY, 2011, 132 (03) : 315 - 325
  • [6] Donor selection for natural killer cell receptor genes leads to superior survival after unrelated transplantation for acute myelogenous leukemia
    Cooley, Sarah
    Weisdorf, Daniel J.
    Guethlein, Lisbeth A.
    Klein, John P.
    Wang, Tao
    Le, Chap T.
    Marsh, Steven G. E.
    Geraghty, Daniel
    Spellman, Stephen
    Haagenson, Michael D.
    Ladner, Martha
    Trachtenberg, Elizabeth
    Parham, Peter
    Miller, Jeffrey S.
    [J]. BLOOD, 2010, 116 (14) : 2411 - 2419
  • [7] Donors with group B KIR haplotypes improve relapse-free survival after unrelated hematopoietic cell transplantation for acute myelogenous leukemia
    Cooley, Sarah
    Trachtenberg, Elizabeth
    Bergemann, Tracy L.
    Saeteurn, Koy
    Klein, John
    Le, Chap T.
    Marsh, Steven G. E.
    Guethlein, Lisbeth A.
    Parham, Peter
    Miller, Jeffrey S.
    Weisdorf, Daniel J.
    [J]. BLOOD, 2009, 113 (03) : 726 - 732
  • [8] Influence of KIR and NK Cell Reconstitution in the Outcomes of Hematopoietic Stem Cell Transplantation
    Gao, Fei
    Ye, Yishan
    Gao, Yang
    Huang, He
    Zhao, Yanmin
    [J]. FRONTIERS IN IMMUNOLOGY, 2020, 11
  • [9] Association of KIR2DS4 and its variant KIR1D with leukemia
    Giebel, S.
    Nowak, I.
    Wojnar, J.
    Krawczyk-Kulis, M.
    Holowiecki, J.
    Kyrcz-Krzemien, S.
    Kusnierczyk, P.
    [J]. LEUKEMIA, 2008, 22 (11) : 2129 - 2130
  • [10] Allele frequency net 2015 update: new features for HLA epitopes, KIR and disease and HLA adverse drug reaction associations
    Gonzalez-Galarza, Faviel F.
    Takeshita, Louise Y. C.
    Santos, Eduardo J. M.
    Kempson, Felicity
    Thomaz Maia, Maria Helena
    Soares da Silva, Andrea Luciana
    Teles e Silva, Andre Luiz
    Ghattaoraya, Gurpreet S.
    Alfirevic, Ana
    Jones, Andrew R.
    Middleton, Derek
    [J]. NUCLEIC ACIDS RESEARCH, 2015, 43 (D1) : D784 - D788