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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

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 thro...

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Main Authors: Neuchel, Christine (Author) , Gowdavally, Sowmya (Author) , Tsamadou, Chrysanthi (Author) , Platzbecker, Uwe (Author) , Sala, Elisa (Author) , Wagner-Drouet, Eva (Author) , Valerius, Thomas (Author) , Kröger, Nicolaus (Author) , Wulf, Gerald (Author) , Einsele, Hermann (Author) , Thurner, Lorenz (Author) , Schaefer-Eckart, Kerstin (Author) , Freitag, Sebastian (Author) , Casper, Jochen (Author) , Dürholt, Mareike (Author) , Kaufmann, Martin (Author) , Hertenstein, Bernd (Author) , Klein, Stefan (Author) , Ringhoffer, Mark (Author) , Frank, Sandra (Author) , Amann, Elisa Maria (Author) , Rode, Immanuel (Author) , Schrezenmeier, Hubert (Author) , Mytilineos, Joannis (Author) , Fürst, Daniel (Author)
Format: Article (Journal)
Language:English
Published: 07 July 2022
In: HLA
Year: 2022, Volume: 100, Issue: 4, Pages: 349-360
ISSN:2059-2310
DOI:10.1111/tan.14733
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1111/tan.14733
Verlag, lizenzpflichtig, Volltext: http://onlinelibrary.wiley.com/doi/abs/10.1111/tan.14733
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Author Notes:Christine Neuchel, Sowmya Gowdavally, Chrysanthi Tsamadou, Uwe Platzbecker, Elisa Sala, Eva Wagner-Drouet, Thomas Valerius, Nicolaus Kröger, Gerald Wulf, Hermann Einsele, Lorenz Thurner, Kerstin Schaefer-Eckart, Sebastian Freitag, Jochen Casper, Mareike Dürholt, Martin Kaufmann, Bernd Hertenstein, Stefan Klein, Mark Ringhoffer, Sandra Frank, Elisa Maria Amann, Immanuel Rode, Hubert Schrezenmeier, Joannis Mytilineos, Daniel Fürst
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Summary: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.
Item Description:Gesehen am 15.08.2023
Physical Description:Online Resource
ISSN:2059-2310
DOI:10.1111/tan.14733

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