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

Frontiers in Immunology

Immunology

Patrycja Skowrońska¹  Wojciech Fidyk²  Małgorzata Sobczyk-Kruszelnicka²  Sebastian Giebel²  Maria Bieniaszewska³  Tomasz Wróbel⁴  Donata Szymczak⁴  Agnieszka Szeremet⁴  Anna Czyż⁴  Maciej Majcherek⁴  Grzegorz W. Basak⁵  Agnieszka Tomaszewska⁵  Iwona Solarska⁶  Barbara Nasiłowska-Adamska⁶  Jagoda Siemaszko⁷  Katarzyna Bogunia-Kubik⁷  Piotr Łacina⁷ 

[1] Cell and Tissue Bank, University Medical Center in Gdansk, Gdansk, Poland;Department of Bone Marrow Transplantation and Hematology-Oncology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice, Poland;Department of Hematology and Transplantology, Medical University of Gdansk, Gdansk, Poland;Department of Hematology, Blood Neoplasms and Bone Marrow Transplantation, Wroclaw Medical University, Wroclaw, Poland;Department of Hematology, Transplantation and Internal Medicine, Medical University of Warsaw, Warsaw, Poland;Institute of Hematology and Blood Transfusion Medicine, Warsaw, Poland;Laboratory of Clinical Immunogenetics and Pharmacogenetics, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland;

关键词: HSCT;    NK cells;    NK cell receptors;    NKG2A;    NKG2C;    HLA-E;    sHLA-E;    transplant outcome;   

DOI  :  10.3389/fimmu.2023.1227897

 received in 2023-05-23, accepted in 2023-09-15,  发布年份 2023

来源: Frontiers

【 摘 要 】

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.

【 授权许可】

Unknown   
Copyright © 2023 Siemaszko, Łacina, Szymczak, Szeremet, Majcherek, Czyż, Sobczyk-Kruszelnicka, Fidyk, Solarska, Nasiłowska-Adamska, Skowrońska, Bieniaszewska, Tomaszewska, Basak, Giebel, Wróbel and Bogunia-Kubik