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Graft-Versus-Host-Disease

The degree of matching at HLA-DPB1 predicts for acute graft-versus-host disease and disease relapse following haematopoietic stem cell transplantation

Summary:

The importance of matching for HLA-DPB1 in unrelated donor haematopoietic stem cell (HSC) transplantation is little understood. Most transplant centres do not, currently, prospectively match for DPB1, but emerging data show that DPB1 matching does play a role in determining outcome. We studied the impact of HLA-DPB1 matching on outcome in 143 recipients of T-cell depletion transplants, who matched with their respective unrelated donors (allelic level) at HLA-A, -B, -C, -DRB1 and -DQB1. Of those matched at DPB1, 47.2% (17/36) developed acute graft-versus-host disease (aGvHD) as compared to 66.3% (55/83) of those who were mismatched. This led to a 19.1% (95% CI 0.1–38.3%) increase in the chance of developing aGvHD in mismatched patients (P=0.049). Relapse of the original disease occurred in 51 recipients; 23 of 37 (62%) matched at both DPB1 alleles, 28 of 82 (34%) were mismatched at one or two DPB1 alleles. Thus, there was a significantly higher relapse rate (P=0.0011) in transplant recipients who matched at both DPB1 alleles. In conclusion, a donor/recipient DPB1 match was associated with a significantly lower incidence of aGvHD and a significantly higher incidence of disease relapse. This study provides further evidence for an immunogenic role of HLA-DPB1 in HSC transplants.

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References

  1. El Kassar N, Legouvello S, Joseph CM et al. High resolution HLA class I and II typing and CTLp frequency in unrelated donor transplantation: a single-institution retrospective study of 69 BMTs. Bone Marrow Transplant 2001; 27: 35–43.

    Article  CAS  Google Scholar 

  2. Petersdorf EW, Gooley TA, Anasetti C et al. Optimizing outcome after unrelated marrow transplantation by comprehensive matching of HLA class I and II alleles in the donor and recipient. Blood 1998; 92: 3515–3520.

    CAS  Google Scholar 

  3. Sasazuki T, Juji T, Morishima Y et al. Effect of matching of class I HLA alleles on clinical outcome after transplantation of hematopoietic stem cells from an unrelated donor. Japan Marrow Donor Program. N Engl J Med 1998; 339: 1177–1185.

    Article  CAS  Google Scholar 

  4. Petersdorf EW, Kollman C, Hurley CK et al. Effect of HLA class II gene disparity on clinical outcome in unrelated donor hematopoietic cell transplantation for chronic myeloid leukemia: the US National Marrow Donor Program Experience. Blood 2001; 98: 2922–2929.

    Article  CAS  Google Scholar 

  5. Marsh SGE, Albert ED, Bodmer WF et al. Nomenclature for factors of the HLA system, 2002. Tissue Antigens (in press).

  6. Marsh SGE, Parham P, Barber LD . The HLA FactsBook 2002; 60: 407–464. Academic Press: London, 2000.

    Google Scholar 

  7. Begovich AB, Moonsamy PV, Mack SJ et al. Genetic variability and linkage disequilibrium within the HLA-DP region: analysis of 15 different populations. Tissue Antigens 2001; 57: 424–439.

    Article  CAS  Google Scholar 

  8. Buchler T, Gallardo D, Rodriguez-Luaces M et al. Frequency of HLA-DPB1 disparities detected by reference strand-mediated conformation analysis in HLA-A, -B, and -DRB1 matched siblings. Hum Immunol 2002; 63: 139–142.

    Article  CAS  Google Scholar 

  9. Nomura N, Ota M, Kato S et al. Severe acute graft-versus-host disease by HLA-DPB1 disparity in recombinant family of bone marrow transplantation between serologically HLA-identical siblings: an application of the polymerase chain reaction – restriction fragment length polymorphism method. Hum Immunol 1991; 32: 261–268.

    Article  CAS  Google Scholar 

  10. Varney MD, Lester S, McCluskey J et al. Matching for HLA DPA1 and DPB1 alleles in unrelated bone marrow transplantation. Hum Immunol 1999; 60: 532–538.

    Article  CAS  Google Scholar 

  11. Petersdorf EW, Gooley T, Malkki M et al. The biological significance of HLA-DP gene variation in haematopoietic cell transplantation. Br J Haematol 2001; 112: 988–994.

    Article  CAS  Google Scholar 

  12. Hurley CK, Baxter-Lowe LA, Begovich AB et al. The extent of HLA class II allele level disparity in unrelated bone marrow transplantation: analysis of 1259 National Marrow Donor Program donor–recipient pairs. Bone Marrow Transplant 2000; 25: 385–393.

    Article  CAS  Google Scholar 

  13. Yu M, Kinkel RP, Weinstock-Guttman B et al. HLA-DP: a class II restriction molecule involved in epitope spreading during the development of multiple sclerosis. Hum Immunol 1998; 59: 15–24.

    Article  CAS  Google Scholar 

  14. Bugawan TL, Angelini G, Larrick J et al. A combination of a particular HLA-DP beta allele and an HLA-DQ heterodimer confers susceptibility to coeliac disease. Nature 1989; 339: 470–473.

    Article  CAS  Google Scholar 

  15. Begovich AB, Bugawan TL, Nepom BS et al. A specific HLA-DP beta allele is associated with pauciarticular juvenile rheumatoid arthritis but not adult rheumatoid arthritis. Proc Natl Acad Sci USA 1989; 86: 9489–9493.

    Article  CAS  Google Scholar 

  16. Richeldi L, Sorrentino R, Saltini C . HLA-DPB1 glutamate 69: a genetic marker of beryllium disease. Science 1993; 262: 242–244.

    Article  CAS  Google Scholar 

  17. Potolicchio I, Mosconi G, Forni A et al. Susceptibility to hard metal lung disease is strongly associated with the presence of glutamate 69 in HLA-DP beta chain. Eur J Immunol 1997; 27: 2741–2743.

    Article  CAS  Google Scholar 

  18. Tonks S, Oza AM, Lister TA, Bodmer JG . Association of HLA-DPB with Hodgkin's disease. Lancet 1992; 340: 968–969.

    Article  CAS  Google Scholar 

  19. Gaschet J, Gallot G, Ibisch C et al. Acute graft-versus-host disease after bone marrow transplantation with a single HLA-DPB1*1001 mismatch: involvement of different TCRBV subsets. Bone Marrow Transplant 1998; 22: 385–392.

    Article  CAS  Google Scholar 

  20. Ibisch C, Gallot G, Vivien R et al. Recognition of leukemic blasts by HLA-DPB1-specific cytotoxic T cell clones: a perspective for adjuvant immunotherapy post-bone marrow transplantation. Bone Marrow Transplant 1999; 23: 1153–1159.

    Article  CAS  Google Scholar 

  21. 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.

    CAS  Google Scholar 

  22. Moreau P, Cesbron A . HLA-DP and allogeneic bone marrow transplantation. Bone Marrow Transplant 1994; 13: 675–681.

    CAS  PubMed  Google Scholar 

  23. Arguello JR, Little AM, Bohan E et al. High resolution HLA class I typing by reference strand mediated conformation analysis (RSCA). Tissue Antigens 1998; 52: 57–66.

    Article  CAS  Google Scholar 

  24. Gyllensten UB, Erlich HA . MHC class II haplotypes and linkage disequilibrium in primates. Hum Immunol 1993; 36: 1–10.

    Article  CAS  Google Scholar 

  25. Kimura A, Dong RP, Harada H, Sasazuki T . DNA typing of HLA class II genes in B-lymphoblastoid cell lines homozygous for HLA. Tissue Antigens 1992; 40: 5–12.

    Article  CAS  Google Scholar 

  26. Ho VT, Soiffer RJ . The history and future of T-cell depletion as graft-versus-host disease prophylaxis for allogeneic hematopoietic stem cell transplantation. Blood 2001; 98: 3192–3204.

    Article  CAS  Google Scholar 

  27. Nicholson I, Varney M, Kanaan C et al. Alloresponses to HLA-DP detected in the primary MLR: correlation with a single amino acid difference. Hum Immunol 1997; 55: 163–169.

    Article  CAS  Google Scholar 

  28. Ferrara GB, Bacigalupo A, Lamparelli T et al. Bone marrow transplantation from unrelated donors: the impact of mismatches with substitutions at position 116 of the human leukocyte antigen class I heavy chain. Blood 2001; 98: 3150–3155.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank the transplant and harvest centres in the UK who have provided us with both blood samples and clinical information on the donors and recipients.

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Shaw, B., Potter, M., Mayor, N. et al. The degree of matching at HLA-DPB1 predicts for acute graft-versus-host disease and disease relapse following haematopoietic stem cell transplantation. Bone Marrow Transplant 31, 1001–1008 (2003). https://doi.org/10.1038/sj.bmt.1704029

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