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Targeted minor histocompatibility antigen typing to estimate graft-versus-host disease after allogeneic haematopoietic stem cell transplantation

Abstract

Graft-versus-host disease (GVHD) is a critical complication after allogeneic haematopoietic stem cell transplantation induced by genetic differences in donor–recipient pairs. Rigorous HLA matching has reduced GVHD, but severe GVHD still occurs. Minor histocompatibility antigens (mHAs) are another source of GVHD inducers. We designed a multi-mHA panel with 35 valid mHA loci and retrospectively analyzed 391 donor–recipient pairs with the anticipation of implementing mHA typing into clinical practice to optimize donor selection. Results showed the total mismatching in mHA loci in this panel, as well as mismatching in the GVH direction in unmatched-related recipients (UMRs) were 1.8 times and 1.3 times as those in matched-sibling recipients (MSRs) (p = 4.1e-4, p = 0.012, respectively). There was no significant association between mHA loci mismatching and grades II-IV acute GVHD (aGVHD), III-IV aGVHD, extensive chronic GVHD (cGVHD), or relapse in neither group. UMRs had an increased cumulative incidence of II-IV aGVHD (p = 0.002), but there was no statistical difference of the incidences in severe aGVHD or cGVHD (p = 0.093; p = 0.930). This is a preliminary study to explore GVHD risks brought by mHA loci mismatching in both unmatched-related recipients and matched-full-sibling recipients. Our results confirmed that stringent HLA matching is the key to reduce the risks for GVHD.

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Fig. 1: Mismatching distribution.
Fig. 2: Mismatching in mHA loci in this panel seems not to affect the risks of GVHD events nor relapse.
Fig. 3: GVHD-related outcomes.

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Acknowledgements

We acknowledge the kind support of all clinicians in the Department of Bone Marrow Transplantation.

Funding

This work was partially supported by grant from the Shandong Nature Science Fund (ZR2016HP02).

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DN interpreted the data, followed up with the patients, and wrote the manuscript. JZ, LL, and XL analyzed the data, graded the GVHD. JW graded the GVHD and guided the study as a clinician. JW, WZ, JC, XZ, and YT performed the sequencing of mHA typing and HLA typing, HL and WT supervised the study and revised the manuscript.

Corresponding authors

Correspondence to Hongxing Liu or Wenjun Tian.

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The authors declare no competing interests.

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Nie, D., Zhang, J., Liu, L. et al. Targeted minor histocompatibility antigen typing to estimate graft-versus-host disease after allogeneic haematopoietic stem cell transplantation. Bone Marrow Transplant (2021). https://doi.org/10.1038/s41409-021-01459-8

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