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Host versus graft HLA-DP1 mismatching promotes graft versus host disease

Bone Marrow Transplantation volume 58, pages 950–952 (2023)Cite this article

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HLA matching is a major determinant of the risk of acute graft versus host disease (GVHD) and the outcome of allogeneic hematopoietic stem cell transplantation (HSCT) [1]. The HLA-DPB1 gene is less polymorphic than other HLA antigens and four groups of alleles have been defined which predict the immunogenicity of mismatching according to a T Cell Epitope (TCE) algorithm [2,3,4]. Non-permissive HLA-mismatches may be uni-directional in either the graft versus host (GVH) or host versus graft (HVG) direction. Several studies have shown that mismatches in both GVH and HVG directions are associated with similar adverse outcomes to bi-directional mismatching including higher rates of GVHD, non-relapse mortality (NRM) and inferior overall survival [2,3,4,5]. These data have been extended more recently to include cohorts containing non-myeloablative transplants with peripheral blood stem cells and in vivo T cell depletion but the results are discordant [6, 7]. Detrimental effects linked to HVG mismatching are not simple to explain but have been ascribed to the persistence of host T cells. Recent pre-clinical studies have highlighted that host resident T cells survive allogeneic transplantation and may elicit cutaneous reactions with features of clinical GVHD, when presented with donor-derived myeloid cells [8,9,10]. In addition, the significance thresholds for reporting HVG effects are potentially influenced by the incidence of GVHD in a particular cohort, which may vary with level of matching, conditioning intensity, use of T cell depletion and stem cell source. Previous reports have included mostly myeloablative transplants (>60%) and either a significant number of ≤9/10 mismatched donors [2,3,4, 6] or BM donors [5, 7].

We re-examined the effect of HVG DP mismatching on GVHD in a retrospective cohort of 183 patients who received transplantation with 10/10 allele matched PBSC, predominately with reduced intensity conditioning and nearly all with T cell depletion.

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Fig. 1: Survival and graft versus host disease in HLA-DP-mismatched transplants.

Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

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Authors and Affiliations

  1. Newcastle University, Newcastle upon Tyne, United Kingdom

    Callum Wright, Ginette Reid, Beverley Clare Lendrem, Venetia Bigley & Matthew Collin

  2. Northern Centre for Bone Marrow Transplantation, Newcastle upon Tyne, United Kingdom

    Callum Wright, Erin Hurst, Amy Publicover, Rachel Luke, Louise Duncan, Venetia Bigley & Matthew Collin

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  1. Callum Wright
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  2. Ginette Reid
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Contributions

CW and MC wrote the manuscript. CW and GR analysed the data. BCL provided statistical support and guidance on the methodology of analysis. RL and LD collected data and reviewed the manuscript. CW, GR, BCL, EH, AP, RL, LD, VB and MC contributed to interpretation of results and reviewed the manuscript.

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Correspondence to Callum Wright.

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Wright, C., Reid, G., Lendrem, B.C. et al. Host versus graft HLA-DP1 mismatching promotes graft versus host disease. Bone Marrow Transplant 58, 950–952 (2023). https://doi.org/10.1038/s41409-023-02003-6

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