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. 2020 Aug 20;38(24):2712-2718.
doi: 10.1200/JCO.20.00265. Epub 2020 Jun 1.

Role of HLA-DP Expression in Graft-Versus-Host Disease After Unrelated Donor Transplantation

Effie W Petersdorf  1   2 , Mats Bengtsson  3 , Dianne De Santis  4 , Valerie Dubois  5 , Katharina Fleischhauer  6 , Ted Gooley  1 , Mary Horowitz  7   8 , J Alejandro Madrigal  9 , Mari Malkki  1 , Caroline McKallor  1 , Yasuo Morishima  10 , Machteld Oudshoorn  11   12 , Stephen R Spellman  13 , Jean Villard  14 , Phil Stevenson  1 , Mary Carrington  15   16 ; the; International Histocompatibility Working Group in Hematopoietic-Cell Transplantation
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Role of HLA-DP Expression in Graft-Versus-Host Disease After Unrelated Donor Transplantation

Effie W Petersdorf et al. J Clin Oncol. .

Abstract

Purpose: The main aim of this study was to evaluate the significance of HLA-DPB1 expression in acute graft-versus-host disease (GVHD) after hematopoietic cell transplantation (HCT) from HLA-A, -B, -C, -DRB1, -DQB1-matched and -mismatched unrelated donors.

Patients and methods: Between January 1, 2017, and January 10, 2019, we assessed 19,136 patients who received HCT from an HLA-A, -B, -C, -DRB1, -DQB1-matched or -mismatched unrelated donor performed in Australia, the European Union, Japan, North America, and the United Kingdom between 1988 and 2016. Among transplant recipients with one HLA-DPB1 mismatch, the patient's mismatched HLA-DPB1 allotype was defined as low or high expression. Multivariable regression models were used to assess risks of GVHD associated with high expression relative to low expression HLA-DPB1 mismatches. The effect of increasing numbers of HLA-DPB1 mismatches on clinical outcome was assessed in HLA-mismatched transplant recipients.

Results: In HLA-A, -B, -C, -DRB1,-DQB1-matched transplant recipients, donor mismatching against one high-expression patient HLA-DPB1 increased moderate (odds ratio [OR], 1.36; P = .001) and severe acute GVHD (OR, 1.32; P = .0016) relative to low-expression patient mismatches, regardless of the expression level of the donor's mismatched HLA-DPB1. Among transplant recipients with one HLA-A, -B, -C, -DRB1, or -DQB1 mismatch, the odds of acute GVHD increased with increasing numbers of HLA-DPB1 mismatches (OR, 1.23 for one; OR, 1.40 for two mismatches relative to zero mismatches for moderate GVHD; OR, 1.19 for one; OR, 1.40 for two mismatches relative to zero for severe GVHD), but not with the level of expression of the patient's mismatched HLA-DPB1 allotype.

Conclusion: The level of expression of patient HLA-DPB1 mismatches informs the risk of GVHD after HLA-A, -B, -C, -DRB1, -DQB1-matched unrelated HCT, and the total number of HLA-DPB1 mismatches informs the risk of GVHD after HLA-mismatched unrelated HCT. Prospective consideration of HLA-DPB1 may help to lower GVHD risks after transplantation.

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References

    1. Petersdorf EW, Hansen JA, Martin PJ, et al. Major-histocompatibility-complex class I alleles and antigens in hematopoietic-cell transplantation. N Engl J Med. 2001;345:1794–1800. - PubMed
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    1. Petersdorf EW, Smith AG, Mickelson EM, et al. The role of HLA-DPB1 disparity in the development of acute graft-versus-host disease following unrelated donor marrow transplantation. Blood. 1993;81:1923–1932. - PubMed
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