Integrating killer cell immunoglobulin-like receptor high-resolution genotyping for predicting transplant outcomes in allogeneic hematopoietic stem cell transplantation
The success of hematopoietic stem cell transplantation (HSCT) partly relies on the beneficial graft-versus-leukemia effect, mediated by alloreactive NK cells through their killer cell immunoglobulin-like receptors (KIR). Conflicting results have been reported regarding the impact of the KIR immunog...
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Ferrata Storti Foundation
2025-07-01
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| Series: | Haematologica |
| Online Access: | https://haematologica.org/article/view/12166 |
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| author | Antonia Schäfer Stéphane Buhler Ticiana D.J. Farias Katherine M. Kichula Helen Baldomero Zuleika Calderin Sollet Sylvie Ferrari-Lacraz Baptiste Micheli Stavroula Masouridi-Levrat Vanessa Mesquita Oliver Kürsteiner Gayathri Nair Jörg Halter Tayfun Güngör Dominik Schneidawind Yves Chalandon Jakob R. Passweg Paul J. Norman Jean Villard |
| author_facet | Antonia Schäfer Stéphane Buhler Ticiana D.J. Farias Katherine M. Kichula Helen Baldomero Zuleika Calderin Sollet Sylvie Ferrari-Lacraz Baptiste Micheli Stavroula Masouridi-Levrat Vanessa Mesquita Oliver Kürsteiner Gayathri Nair Jörg Halter Tayfun Güngör Dominik Schneidawind Yves Chalandon Jakob R. Passweg Paul J. Norman Jean Villard |
| author_sort | Antonia Schäfer |
| collection | DOAJ |
| description |
The success of hematopoietic stem cell transplantation (HSCT) partly relies on the beneficial graft-versus-leukemia effect, mediated by alloreactive NK cells through their killer cell immunoglobulin-like receptors (KIR). Conflicting results have been reported regarding the impact of the KIR immunogenetic system on HSCT outcomes with a scarcity of data interrogating the effect of KIR allelic polymorphism. With the aim to fill this gap, donor KIR genes derived from a national cohort of 1247 HLA-matched transplanted donor/recipient pairs were determined at a high-resolution and tested in Cox proportional hazards models. Donor/recipient (D/R) pairs bearing a KIR2DS4*00101 – HLA-C1/C2/A11 interaction showed a significant detrimental impact on progression-free survival (PFS), overall survival (OS), transplant-related mortality (TRM) and chronic graft-versus-host disease (cGvHD) in multivariable analysis. Strong KIR2DL2/L3 – HLAC1 and especially KIR2DL3*00501 and *015 interactions showed a significant increase in the incidence of cGvHD compared to missing ligand D/R pairs. Highly inhibiting KIR3DL1 – HLA-B and HLA-A (Bw4) interactions were associated with a reduced relapse incidence as compared to weak and non-inhibiting interactions. Our study indicates that high-resolution KIR genotyping informs post-transplant outcomes with a seemingly higher protection of educated NK cells.
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| format | Article |
| id | doaj-art-54503a9b488f4a718134eeea724c3f59 |
| institution | Kabale University |
| issn | 0390-6078 1592-8721 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Ferrata Storti Foundation |
| record_format | Article |
| series | Haematologica |
| spelling | doaj-art-54503a9b488f4a718134eeea724c3f592025-08-20T03:28:17ZengFerrata Storti FoundationHaematologica0390-60781592-87212025-07-01999110.3324/haematol.2024.287061Integrating killer cell immunoglobulin-like receptor high-resolution genotyping for predicting transplant outcomes in allogeneic hematopoietic stem cell transplantationAntonia Schäfer0Stéphane Buhler1Ticiana D.J. Farias2Katherine M. Kichula3Helen Baldomero4Zuleika Calderin Sollet5Sylvie Ferrari-Lacraz6Baptiste Micheli7Stavroula Masouridi-Levrat8Vanessa Mesquita9Oliver Kürsteiner10Gayathri Nair11Jörg Halter12Tayfun Güngör13Dominik Schneidawind14Yves Chalandon15Jakob R. Passweg16Paul J. Norman17Jean Villard18Transplantation Immunology Unit and National Reference Laboratory for Histocompatibility, Department of Diagnostic, Geneva University Hospitals, GenevaTransplantation Immunology Unit and National Reference Laboratory for Histocompatibility, Department of Diagnostic, Geneva University Hospitals, GenevaDepartment of Biomedical Informatics, and Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, CODepartment of Biomedical Informatics, and Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, CODivision of Hematology, Basel University Hospital, BaselTransplantation Immunology Unit and National Reference Laboratory for Histocompatibility, Department of Diagnostic, Geneva University Hospitals, GenevaTransplantation Immunology Unit and National Reference Laboratory for Histocompatibility, Department of Diagnostic, Geneva University Hospitals, GenevaGenetic Medicine Division, Department of Diagnostic, Geneva University Hospitals, GenevaDivision of Hematology, Department of Oncology, Geneva University Hospitals, GenevaDepartment of Medical Oncology and Hematology, University Hospital Zurich, ZurichSwiss Blood Stem Cells Registry, Blutspende SRK Schweiz, BernSwiss Blood Stem Cells Registry, Blutspende SRK Schweiz, BernDivision of Hematology, Basel University Hospital, BaselDepartment of Stem Cell Transplantation, University Children’s Hospital Zurich, CIC 334, ZurichDepartment of Medical Oncology and Hematology, University Hospital Zurich, ZurichDivision of Hematology, Department of Oncology, Geneva University Hospitals, GenevaDivision of Hematology, Basel University Hospital, BaselDepartment of Biomedical Informatics, and Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, COTransplantation Immunology Unit and National Reference Laboratory for Histocompatibility, Department of Diagnostic, Geneva University Hospitals, Geneva The success of hematopoietic stem cell transplantation (HSCT) partly relies on the beneficial graft-versus-leukemia effect, mediated by alloreactive NK cells through their killer cell immunoglobulin-like receptors (KIR). Conflicting results have been reported regarding the impact of the KIR immunogenetic system on HSCT outcomes with a scarcity of data interrogating the effect of KIR allelic polymorphism. With the aim to fill this gap, donor KIR genes derived from a national cohort of 1247 HLA-matched transplanted donor/recipient pairs were determined at a high-resolution and tested in Cox proportional hazards models. Donor/recipient (D/R) pairs bearing a KIR2DS4*00101 – HLA-C1/C2/A11 interaction showed a significant detrimental impact on progression-free survival (PFS), overall survival (OS), transplant-related mortality (TRM) and chronic graft-versus-host disease (cGvHD) in multivariable analysis. Strong KIR2DL2/L3 – HLAC1 and especially KIR2DL3*00501 and *015 interactions showed a significant increase in the incidence of cGvHD compared to missing ligand D/R pairs. Highly inhibiting KIR3DL1 – HLA-B and HLA-A (Bw4) interactions were associated with a reduced relapse incidence as compared to weak and non-inhibiting interactions. Our study indicates that high-resolution KIR genotyping informs post-transplant outcomes with a seemingly higher protection of educated NK cells. https://haematologica.org/article/view/12166 |
| spellingShingle | Antonia Schäfer Stéphane Buhler Ticiana D.J. Farias Katherine M. Kichula Helen Baldomero Zuleika Calderin Sollet Sylvie Ferrari-Lacraz Baptiste Micheli Stavroula Masouridi-Levrat Vanessa Mesquita Oliver Kürsteiner Gayathri Nair Jörg Halter Tayfun Güngör Dominik Schneidawind Yves Chalandon Jakob R. Passweg Paul J. Norman Jean Villard Integrating killer cell immunoglobulin-like receptor high-resolution genotyping for predicting transplant outcomes in allogeneic hematopoietic stem cell transplantation Haematologica |
| title | Integrating killer cell immunoglobulin-like receptor high-resolution genotyping for predicting transplant outcomes in allogeneic hematopoietic stem cell transplantation |
| title_full | Integrating killer cell immunoglobulin-like receptor high-resolution genotyping for predicting transplant outcomes in allogeneic hematopoietic stem cell transplantation |
| title_fullStr | Integrating killer cell immunoglobulin-like receptor high-resolution genotyping for predicting transplant outcomes in allogeneic hematopoietic stem cell transplantation |
| title_full_unstemmed | Integrating killer cell immunoglobulin-like receptor high-resolution genotyping for predicting transplant outcomes in allogeneic hematopoietic stem cell transplantation |
| title_short | Integrating killer cell immunoglobulin-like receptor high-resolution genotyping for predicting transplant outcomes in allogeneic hematopoietic stem cell transplantation |
| title_sort | integrating killer cell immunoglobulin like receptor high resolution genotyping for predicting transplant outcomes in allogeneic hematopoietic stem cell transplantation |
| url | https://haematologica.org/article/view/12166 |
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