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Impact of MICA and NKG2D polymorphisms in HLA-fully matched related and unrelated hematopoietic stem cell transplantation

Bone Marrow Transplantation volume 53, pages 918–922 (2018)Cite this article

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Major histocompatibility complex (MHC) class I-related chain A gene (MICA) is a highly polymorphic gene located on the short arm of chromosome 6 (6p21.33), close to the HLA-B locus. MICA encodes a cell-stress-inducible glycoprotein (exons 2–4 of MICA for synthesis of three extracellular domains, and exon 5 for transmembrane domain), that mediates activation of NKG2D receptor expression on NK cells, CD8+ αβ and γδ T cells, and NK T cells [1, 2]. The MICA polymorphism (MICA-129 and MICA A5.1) has been shown to influence NKG2D signaling [3] and NKG2D polymorphisms are associated with natural cytotoxic activity (see Supplemental Data for details) [4].

Allogenic hematopoietic stem cell transplantation (HSCT) is a well-established treatment for a variety of diseases affecting the immune and hematopoietic systems. Adverse post-HSCT clinical outcomes are still frequent, and notably include graft-versus-host disease (GVHD). Ensuring a high degree of donor-recipient HLA matching (i.e., 10 out of 10 matched HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 alleles) is one of the most important ways of decreasing the risk of post-HSCT complications. The role of MICA in this context has been examined, especially with regard to the impact of MICA-129 val/val on the incidence of chronic GVHD (cGVHD) [5], and the correlation between MICA-129 mismatches and poor disease-free survival [6]. Moreover, in a cohort of 922 unrelated donor-recipient pairs matched for 10 out of 10 HLA alleles, MICA mismatches were associated with a significantly elevated incidence of grade III–IV acute GVHD (aGVHD), cGVHD, and relapse-free mortality (RFS).[7]

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References

  1. Visser CJ, Tilanus MG, Tatari Z, van der Zwan AW, Bakker R, Rozemuller EH, et al. Sequencing-based typing of MICA reveals 33 alleles: a study on linkage with classical HLA genes. Immunogenetics. 1999;49:561–6.

    Article  PubMed  CAS  Google Scholar 

  2. Bauer S, Groh V, Wu J, Steinle A, Phillips JH, Lanier LL, et al. Activation of NK cells and T cells by NKG2D, a receptor for stress-inducible MICA. Science. 1999;285:727–9.

    Article  PubMed  CAS  Google Scholar 

  3. Isernhagen A, Malzahn D, Viktorova E, Elsner L, Monecke S, von Bonin F, et al. The MICA-129 dimorphism affects NKG2D signaling and outcome of hematopoietic stem cell transplantation. EMBO Mol Med. 2015;7:1480–502.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  4. Hayashi T, Imai K, Morishita Y, Hayashi I, Kusunoki Y, Nakachi K. Identification of the NKG2D haplotypes associated with natural cytotoxic activity of peripheral blood lymphocytes and cancer immunosurveillance. Cancer Res. 2006;66:563–70.

    Article  PubMed  CAS  Google Scholar 

  5. Boukouaci W, Busson M, Peffault de Latour R, Rocha V, Suberbielle C, Bengoufa D, et al. MICA-129 genotype, soluble MICA, and anti-MICA antibodies as biomarkers of chronic graft-versus-host disease. Blood. 2009;114:5216–24.

    Article  PubMed  CAS  Google Scholar 

  6. Fuerst D, Neuchel C, Niederwieser D, Bunjes D, Gramatzki M, Wagner E, et al. Matching for the MICA-129 polymorphism is beneficial in unrelated hematopoietic stem cell transplantation. Blood. 2016;128:3169–76.

    PubMed  CAS  Google Scholar 

  7. Carapito R, Jung N, Kwemou M, Untrau M, Michel S, Pichot A et al. Matching for the nonconventional MHC-I gene significantly reduces the incidence of acute and chronic GVHD. Blood. 2016;128:1979-1986.

  8. Ruggeri L, Capanni M, Urbani E, Perruccio K, Shlomchik WD, Tosti A, et al. Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants. Science. 2002;295:2097–100.

    Article  PubMed  CAS  Google Scholar 

  9. Olson JA, Leveson-Gower DB, Gill S, Baker J, Beilhack A, Negrin RS. NK cells mediate reduction of GVHD by inhibiting activated, alloreactive T cells while retaining GVT effects. Blood. 2010;115:4293–301.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  10. Suemizu H, Radosavljevic M, Kimura M, Sadahiro S, Yoshimura S, Bahram S, et al. A basolateral sorting motif in the MICA cytoplasmic tail. Proc Natl Acad Sci USA. 2002;99:2971–6.

    Article  PubMed  CAS  Google Scholar 

  11. Groh V, Wu J, Yee C, Spies T. Tumour-derived soluble MIC ligands impair expression of NKG2D and T-cell activation. Nature. 2002;419:734–8.

    Article  PubMed  CAS  Google Scholar 

  12. Ashiru O, López-Cobo S, Fernández-Messina L, Pontes-Quero S, Pandolfi R, Reyburn HT, et al. A GPI anchor explains the unique biological features of the common NKG2D-ligand allele MICA*008. Biochem J. 2013;454:295–302.

    Article  PubMed  CAS  Google Scholar 

  13. Anderson E, Grzywacz B, Wang H, Wang T, Haagenson M, Spellman S, et al. Limited role of MHC class I chain-related gene A (MICA) typing in assessing graft-versus-host disease risk after fully human leukocyte antigen-matched unrelated donor transplantation. Blood. 2009;114:4753–4.

    Article  PubMed  CAS  Google Scholar 

  14. Espinoza JL, Takami A, Onizuka M, Sao H, Akiyama H, Miyamura K, et al. Japan Marrow Donor Program. NKG2D gene polymorphism has a significant impact on transplant outcomes after HLA-fully-matched unrelated bone marrow transplantation for standard risk hematologic malignancies. Haematologica. 2009;94:1427–34.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  15. Kordelas L, Steckel NK, Horn PA, Beelen DW, Rebmann V. The activating NKG2C receptor is significantly reduced in NK cells after allogeneic stem cell transplantation in patients with severe graft-versus-host disease. Int J Mol Sci. 2016;17:E1797.

    Article  PubMed  CAS  Google Scholar 

  16. Cooper MA, Fehniger TA, Fuchs A, Colonna M, Caligiuri MA. NK cell and DC interactions. Trends Immunol. 2004;25:47–52.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

We thank Professor Antoine Toubert (Institut Universitaire d’Hématologie, Hôpital Saint-Louis, APHP, INSERM UMR-1160, Paris, France) for critically reviewing the manuscript. This work was funded by Amiens University Medical Center (Amiens, France) as part of the French government’s program for hospital-based clinical research.

Author contributions

MJA, JD, and NG designed and performed experiments, analyzed and interpreted data, and wrote the paper; PM and MD performed the statistical analysis; AC, LG, and JPM provided clinical data and reviewed the manuscript for critical content.

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Authors and Affiliations

  1. Department of Hematology and Histocompatibility, Amiens University Medical Center, Amiens, France

    Marie-Joelle Apithy, Judith Desoutter, Loïc Garçon & Nicolas Guillaume

  2. EA 4666, Jules Verne University of Picardie, Amiens, France

    Marie-Joelle Apithy, Loïc Garçon, Jean-Pierre Marolleau & Nicolas Guillaume

  3. Department of Clinical Hematology and Cellular Therapy, Amiens University Medical Center, Amiens, France

    Amandine Charbonnier, Judith Desoutter, Pierre Morel & Jean-Pierre Marolleau

  4. Division of Clinical Research and Innovation, Amiens University Medical Center, Amiens, France

    Momar Diouf

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  1. Marie-Joelle Apithy
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Correspondence to Nicolas Guillaume.

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Apithy, MJ., Charbonnier, A., Desoutter, J. et al. Impact of MICA and NKG2D polymorphisms in HLA-fully matched related and unrelated hematopoietic stem cell transplantation. Bone Marrow Transplant 53, 918–922 (2018). https://doi.org/10.1038/s41409-017-0083-3

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