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In Vitro and In Vivo Assessment of T, B and Myeloid Cells Suppressive Activity and Humoral Responses from Transplant Recipients
Published on: August 12, 2017
Integrating killer cell immunoglobulin-like receptor highresolution genotyping for predicting transplant outcomes in
Antonia Schäfer1, Stéphane Buhler1, Ticiana D J Farias2
1Transplantation 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 natural killer 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 of filling this gap, donor KIR genes derived from a national cohort of 1,247 HLA-matched transplanted donor/recipient pairs were determined at a high-resolution and tested in Cox proportional hazards models. Donor/recipient pairs bearing a KIR2DS4*00101-HLA-C1/C2/A11 interaction showed a significant detrimental impact on progression-free survival, overall survival, transplant-related mortality and chronic graft-versus-host disease in multivariable analysis. Strong KIR2DL2/L3-HLA-C1 and especially KIR2DL3*00501 and *015 interactions showed a significant increase in the incidence of chronic graft-versus-host disease compared to donor/recipient pairs with missing ligands. Strongly 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 natural killer cells.
The success of hematopoietic stem cell transplantation (HSCT) partly relies on the beneficial graft-versus-leukemia effect, mediated by alloreactive natural killer 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 of filling this gap, donor KIR genes derived from a national cohort of 1,247 HLA-matched transplanted donor/recipient pairs were determined at a high-resolution and tested in Cox proportional hazards models. Donor/recipient pairs bearing a KIR2DS4*00101-HLA-C1/C2/A11 interaction showed a significant detrimental impact on progression-free survival, overall survival, transplant-related mortality and chronic graft-versus-host disease in multivariable analysis. Strong KIR2DL2/L3-HLA-C1 and especially KIR2DL3*00501 and *015 interactions showed a significant increase in the incidence of chronic graft-versus-host disease compared to donor/recipient pairs with missing ligands. Strongly 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 natural killer cells.
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