Higher risk for chronic graft-versus-host disease (GvHD) in HLA-G mismatched transplants following allogeneic hematopoietic stem cell transplantation: A retrospective study
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Higher risk for chronic graft-versus-host disease (GvHD) in HLA-G mismatched transplants following allogeneic hematopoietic stem cell transplantation: A retrospective study. / Neuchel, Christine; Gowdavally, Sowmya; Tsamadou, Chrysanthi; Platzbecker, Uwe; Sala, Elisa; Wagner-Drouet, Eva; Valerius, Thomas; Kröger, Nicolaus; Wulf, Gerald; Einsele, Hermann; Thurner, Lorenz; Schaefer-Eckart, Kerstin; Freitag, Sebastian; Casper, Jochen; Dürholt, Mareike; Kaufmann, Martin; Hertenstein, Bernd; Klein, Stefan; Ringhoffer, Mark; Frank, Sandra; Amann, Elisa Maria; Rode, Immanuel; Schrezenmeier, Hubert; Mytilineos, Joannis; Fürst, Daniel.
In: HLA, Vol. 100, No. 4, 10.2022, p. 349-360.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Higher risk for chronic graft-versus-host disease (GvHD) in HLA-G mismatched transplants following allogeneic hematopoietic stem cell transplantation: A retrospective study
AU - Neuchel, Christine
AU - Gowdavally, Sowmya
AU - Tsamadou, Chrysanthi
AU - Platzbecker, Uwe
AU - Sala, Elisa
AU - Wagner-Drouet, Eva
AU - Valerius, Thomas
AU - Kröger, Nicolaus
AU - Wulf, Gerald
AU - Einsele, Hermann
AU - Thurner, Lorenz
AU - Schaefer-Eckart, Kerstin
AU - Freitag, Sebastian
AU - Casper, Jochen
AU - Dürholt, Mareike
AU - Kaufmann, Martin
AU - Hertenstein, Bernd
AU - Klein, Stefan
AU - Ringhoffer, Mark
AU - Frank, Sandra
AU - Amann, Elisa Maria
AU - Rode, Immanuel
AU - Schrezenmeier, Hubert
AU - Mytilineos, Joannis
AU - Fürst, Daniel
N1 - © 2022 The Authors. HLA: Immune Response Genetics published by John Wiley & Sons Ltd.
PY - 2022/10
Y1 - 2022/10
N2 - INTRODUCTION: Graft-versus-host disease (GvHD) is a major complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and is highly influenced by the degree of HLA matching between recipient and donor. The HLA-class Ib molecule HLA-G has been shown to promote tolerogenicity through its interaction with inhibitory receptors found on several immunocompetent cells. We hypothesized that in an allo-HSCT setting, HLA-G mismatches may negatively impact the HLA-G-mediated tolerogenicity either due to inefficient interaction with the inhibitory receptors of the transplanted immune cells or due to direct allorecognition of mismatched HLA-G on host cells by the immune cells of the donor.METHODS: In order to explore this hypothesis, we investigated the impact of HLA-G mismatching in 2.083 10/10 matched high resolution HLA-typed allo-HSCT transplants.RESULTS: We found that the risk of chronic GvHD was significantly higher in HLA-G-mismatched transplant cases as compared with the HLA-G-matched control group (HR: 1.46, 95%CI = 1.11-1.91, p = 0.006). Sub-analysis of the mismatch vector revealed that this effect was only detectable in the GvH (HR: 1.89, 95%CI 1.39-2.57, p < 0.001) but not the HvG direction (HR: 1.01, 95%CI = 0.63-1.63, p = 0.967). In addition, the negative impact of HLA-G mismatching on chronic GvHD was only significant in younger patients (<30y HR: 3.02, 95%CI = 1.25-7.28, p = 0.014; >29y HR: 1.28, 95%CI = 0.94-1.72, p = 0.113).DISCUSSION: Our results indicate that HLA-G mismatches may contribute to the onset of chronic GvHD, especially in younger patients and should therefore be avoided when possible.
AB - INTRODUCTION: Graft-versus-host disease (GvHD) is a major complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and is highly influenced by the degree of HLA matching between recipient and donor. The HLA-class Ib molecule HLA-G has been shown to promote tolerogenicity through its interaction with inhibitory receptors found on several immunocompetent cells. We hypothesized that in an allo-HSCT setting, HLA-G mismatches may negatively impact the HLA-G-mediated tolerogenicity either due to inefficient interaction with the inhibitory receptors of the transplanted immune cells or due to direct allorecognition of mismatched HLA-G on host cells by the immune cells of the donor.METHODS: In order to explore this hypothesis, we investigated the impact of HLA-G mismatching in 2.083 10/10 matched high resolution HLA-typed allo-HSCT transplants.RESULTS: We found that the risk of chronic GvHD was significantly higher in HLA-G-mismatched transplant cases as compared with the HLA-G-matched control group (HR: 1.46, 95%CI = 1.11-1.91, p = 0.006). Sub-analysis of the mismatch vector revealed that this effect was only detectable in the GvH (HR: 1.89, 95%CI 1.39-2.57, p < 0.001) but not the HvG direction (HR: 1.01, 95%CI = 0.63-1.63, p = 0.967). In addition, the negative impact of HLA-G mismatching on chronic GvHD was only significant in younger patients (<30y HR: 3.02, 95%CI = 1.25-7.28, p = 0.014; >29y HR: 1.28, 95%CI = 0.94-1.72, p = 0.113).DISCUSSION: Our results indicate that HLA-G mismatches may contribute to the onset of chronic GvHD, especially in younger patients and should therefore be avoided when possible.
KW - Alleles
KW - Graft vs Host Disease
KW - HLA-G Antigens
KW - Hematopoietic Stem Cell Transplantation/adverse effects
KW - Humans
KW - Leukemia, Myeloid, Acute
KW - Retrospective Studies
U2 - 10.1111/tan.14733
DO - 10.1111/tan.14733
M3 - SCORING: Journal article
C2 - 35799419
VL - 100
SP - 349
EP - 360
JO - HLA
JF - HLA
SN - 2059-2302
IS - 4
ER -
