Significance of HLA-E and its two NKG2 receptors in development of complications after allogeneic transplantation of hematopoietic stem cells

Transplantation of hematopoietic stem cells (HSCT) is a procedure commonly used in treatment of various haematological disorders which is associated with significantly improved survival rates. However, one of its drawbacks is the possibility of development of post-transplant complications, including...

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Main Authors: Jagoda Siemaszko, Piotr Łacina, Donata Szymczak, Agnieszka Szeremet, Maciej Majcherek, Anna Czyż, Małgorzata Sobczyk-Kruszelnicka, Wojciech Fidyk, Iwona Solarska, Barbara Nasiłowska-Adamska, Patrycja Skowrońska, Maria Bieniaszewska, Agnieszka Tomaszewska, Grzegorz W. Basak, Sebastian Giebel, Tomasz Wróbel, Katarzyna Bogunia-Kubik
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-10-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2023.1227897/full
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author Jagoda Siemaszko
Piotr Łacina
Donata Szymczak
Agnieszka Szeremet
Maciej Majcherek
Anna Czyż
Małgorzata Sobczyk-Kruszelnicka
Wojciech Fidyk
Iwona Solarska
Barbara Nasiłowska-Adamska
Patrycja Skowrońska
Maria Bieniaszewska
Agnieszka Tomaszewska
Grzegorz W. Basak
Sebastian Giebel
Tomasz Wróbel
Katarzyna Bogunia-Kubik
author_facet Jagoda Siemaszko
Piotr Łacina
Donata Szymczak
Agnieszka Szeremet
Maciej Majcherek
Anna Czyż
Małgorzata Sobczyk-Kruszelnicka
Wojciech Fidyk
Iwona Solarska
Barbara Nasiłowska-Adamska
Patrycja Skowrońska
Maria Bieniaszewska
Agnieszka Tomaszewska
Grzegorz W. Basak
Sebastian Giebel
Tomasz Wróbel
Katarzyna Bogunia-Kubik
author_sort Jagoda Siemaszko
collection DOAJ
description Transplantation of hematopoietic stem cells (HSCT) is a procedure commonly used in treatment of various haematological disorders which is associated with significantly improved survival rates. However, one of its drawbacks is the possibility of development of post-transplant complications, including acute and chronic graft-versus-host disease (GvHD) or CMV infection. Various studies suggested that NK cells and their receptors may affect the transplant outcome. In the present study, patients and donors were found to significantly differ in the distribution of the NKG2A rs7301582 genetic variants – recipients carried the C allele more often than their donors (0.975 vs 0.865, p<0.0001). Increased soluble HLA-E (sHLA-E) levels detected in recipients’ serum 30 days after transplantation seemed to play a prognostic and protective role. It was observed that recipients with higher sHLA-E levels were less prone to chronic GvHD (11.65 vs 6.33 pg/mL, p=0.033) or more severe acute GvHD grades II-IV (11.07 vs 8.04 pg/mL, p=0.081). Our results also showed an unfavourable role of HLA-E donor-recipient genetic incompatibility in CMV infection development after transplantation (OR=5.92, p=0.014). Frequencies of NK cells (both CD56dim and CD56bright) expressing NKG2C were elevated in recipients who developed CMV, especially 30 and 90 days post-transplantation (p<0.03). Percentages of NKG2C+ NK cells lacking NKG2A expression were also increased in these patients. Moreover, recipients carrying a NKG2C deletion characterized with decreased frequency of NKG2C+ NK cells (p<0.05). Our study confirms the importance of NK cells in the development of post-transplant complications and highlights the effect of HLA-E and NKG2C genetic variants, sHLA-E serum concentration, as well as NKG2C surface expression on transplant outcome.
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spelling doaj.art-58bff34f811c4caa8bfad5c758ba0dca2023-10-13T05:46:05ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-10-011410.3389/fimmu.2023.12278971227897Significance of HLA-E and its two NKG2 receptors in development of complications after allogeneic transplantation of hematopoietic stem cellsJagoda Siemaszko0Piotr Łacina1Donata Szymczak2Agnieszka Szeremet3Maciej Majcherek4Anna Czyż5Małgorzata Sobczyk-Kruszelnicka6Wojciech Fidyk7Iwona Solarska8Barbara Nasiłowska-Adamska9Patrycja Skowrońska10Maria Bieniaszewska11Agnieszka Tomaszewska12Grzegorz W. Basak13Sebastian Giebel14Tomasz Wróbel15Katarzyna Bogunia-Kubik16Laboratory of Clinical Immunogenetics and Pharmacogenetics, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, PolandLaboratory of Clinical Immunogenetics and Pharmacogenetics, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, PolandDepartment of Hematology, Blood Neoplasms and Bone Marrow Transplantation, Wroclaw Medical University, Wroclaw, PolandDepartment of Hematology, Blood Neoplasms and Bone Marrow Transplantation, Wroclaw Medical University, Wroclaw, PolandDepartment of Hematology, Blood Neoplasms and Bone Marrow Transplantation, Wroclaw Medical University, Wroclaw, PolandDepartment of Hematology, Blood Neoplasms and Bone Marrow Transplantation, Wroclaw Medical University, Wroclaw, PolandDepartment of Bone Marrow Transplantation and Hematology-Oncology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice, PolandDepartment of Bone Marrow Transplantation and Hematology-Oncology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice, PolandInstitute of Hematology and Blood Transfusion Medicine, Warsaw, PolandInstitute of Hematology and Blood Transfusion Medicine, Warsaw, PolandCell and Tissue Bank, University Medical Center in Gdansk, Gdansk, PolandDepartment of Hematology and Transplantology, Medical University of Gdansk, Gdansk, PolandDepartment of Hematology, Transplantation and Internal Medicine, Medical University of Warsaw, Warsaw, PolandDepartment of Hematology, Transplantation and Internal Medicine, Medical University of Warsaw, Warsaw, PolandDepartment of Bone Marrow Transplantation and Hematology-Oncology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice, PolandDepartment of Hematology, Blood Neoplasms and Bone Marrow Transplantation, Wroclaw Medical University, Wroclaw, PolandLaboratory of Clinical Immunogenetics and Pharmacogenetics, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, PolandTransplantation of hematopoietic stem cells (HSCT) is a procedure commonly used in treatment of various haematological disorders which is associated with significantly improved survival rates. However, one of its drawbacks is the possibility of development of post-transplant complications, including acute and chronic graft-versus-host disease (GvHD) or CMV infection. Various studies suggested that NK cells and their receptors may affect the transplant outcome. In the present study, patients and donors were found to significantly differ in the distribution of the NKG2A rs7301582 genetic variants – recipients carried the C allele more often than their donors (0.975 vs 0.865, p<0.0001). Increased soluble HLA-E (sHLA-E) levels detected in recipients’ serum 30 days after transplantation seemed to play a prognostic and protective role. It was observed that recipients with higher sHLA-E levels were less prone to chronic GvHD (11.65 vs 6.33 pg/mL, p=0.033) or more severe acute GvHD grades II-IV (11.07 vs 8.04 pg/mL, p=0.081). Our results also showed an unfavourable role of HLA-E donor-recipient genetic incompatibility in CMV infection development after transplantation (OR=5.92, p=0.014). Frequencies of NK cells (both CD56dim and CD56bright) expressing NKG2C were elevated in recipients who developed CMV, especially 30 and 90 days post-transplantation (p<0.03). Percentages of NKG2C+ NK cells lacking NKG2A expression were also increased in these patients. Moreover, recipients carrying a NKG2C deletion characterized with decreased frequency of NKG2C+ NK cells (p<0.05). Our study confirms the importance of NK cells in the development of post-transplant complications and highlights the effect of HLA-E and NKG2C genetic variants, sHLA-E serum concentration, as well as NKG2C surface expression on transplant outcome.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1227897/fullHSCTNK cellsNK cell receptorsNKG2ANKG2CHLA-E
spellingShingle Jagoda Siemaszko
Piotr Łacina
Donata Szymczak
Agnieszka Szeremet
Maciej Majcherek
Anna Czyż
Małgorzata Sobczyk-Kruszelnicka
Wojciech Fidyk
Iwona Solarska
Barbara Nasiłowska-Adamska
Patrycja Skowrońska
Maria Bieniaszewska
Agnieszka Tomaszewska
Grzegorz W. Basak
Sebastian Giebel
Tomasz Wróbel
Katarzyna Bogunia-Kubik
Significance of HLA-E and its two NKG2 receptors in development of complications after allogeneic transplantation of hematopoietic stem cells
Frontiers in Immunology
HSCT
NK cells
NK cell receptors
NKG2A
NKG2C
HLA-E
title Significance of HLA-E and its two NKG2 receptors in development of complications after allogeneic transplantation of hematopoietic stem cells
title_full Significance of HLA-E and its two NKG2 receptors in development of complications after allogeneic transplantation of hematopoietic stem cells
title_fullStr Significance of HLA-E and its two NKG2 receptors in development of complications after allogeneic transplantation of hematopoietic stem cells
title_full_unstemmed Significance of HLA-E and its two NKG2 receptors in development of complications after allogeneic transplantation of hematopoietic stem cells
title_short Significance of HLA-E and its two NKG2 receptors in development of complications after allogeneic transplantation of hematopoietic stem cells
title_sort significance of hla e and its two nkg2 receptors in development of complications after allogeneic transplantation of hematopoietic stem cells
topic HSCT
NK cells
NK cell receptors
NKG2A
NKG2C
HLA-E
url https://www.frontiersin.org/articles/10.3389/fimmu.2023.1227897/full
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