Matching for the MICA-129 polymorphism is beneficial in unrelated hematopoietic stem cell transplantation

Fuerst, Daniel; Neuchel, Christine; Niederwieser, Dietger; Bunjes, Donald; Gramatzki, Martin; Wagner, Eva; Wulf, Gerald; Glaß, Bertram; Pfreundschuh, Michael; Einsele, Hermann; Arnold, Renate; Stuhler, Gernot; Schaefer‐Eckart, Kerstin; Freitag, Sebastian; Casper, Jochen; Kaufmann, Martin; Wattad, Mohammed; Hertenstein, Bernd; Klein, Stefan; Ringhoffer, Mark; Mytilineos, D; Tsamadou, Chrysanthi; Mueller, Carlheinz; Schrezenmeier, Hubert; Mytilineos, Joannis

doi:10.1182/blood-2016-05-716357

Cited by 41 publications

(56 citation statements)

References 40 publications

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“…Other studies have specifically analyzed the influence of the MICA gene by three different approaches: (i) focused analysis of the genotype of a single polymorphism at amino acid position 129 in patients (12, 15), (ii) matching of donors and patients genotypes at the same position; 129 (14), and (iii) matching of donor and patients at the MICA allele level (13, 16, 30, 31). …”

Section: Genetic Polymorphism Of Nkg2d and Nkg2dlmentioning

confidence: 99%

“…More recently, a group analyzed not only the MICA-129 genotype of the patient but also the one of the donor and by this mean the role of the matching of donor and recipients at this position with respect to various clinical outcomes after unrelated HCT (14). They analyzed 2,172 patients that underwent unrelated HCT with donors HLA-matched at various grades (10/10, 9/10, and 8/10).…”

Section: Genetic Polymorphism Of Nkg2d and Nkg2dlmentioning

confidence: 99%

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Natural Killer Group 2, Member D/NKG2D Ligands in Hematopoietic Cell Transplantation

et al. 2017

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Natural killer group 2, member D (NKG2D) is an invariant activatory receptor present on subsets of natural killer and T lymphocytes. It stimulates the cytolytic effector response upon engagement of its various stress-induced ligands NKG2D ligands (NKG2DL). Malignant transformation and conditioning treatment prior to hematopoietic cell transplantation (HCT) are stress factors leading to the activation of the NKG2D/NKG2DL signaling in clinical settings. In the context of HCT, NKG2D-bearing cells can kill both tumor and healthy cells expressing NKG2DL. The NKG2D/NKG2DL engagement has therefore a key role in the regulation of one of the most salient issues in allogeneic HCT, i.e., maintaining a balance between graft-vs.-leukemia effect and graft-vs.-host disease. The present review summarizes the current state of our knowledge pertaining to the role of the NKG2D and NKG2DL in HCT.

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Section: Genetic Polymorphism Of Nkg2d and Nkg2dlmentioning

confidence: 99%

Section: Genetic Polymorphism Of Nkg2d and Nkg2dlmentioning

confidence: 99%

Natural Killer Group 2, Member D/NKG2D Ligands in Hematopoietic Cell Transplantation

et al. 2017

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“…These results suggest that when HLA-A, B, C, DRB1 or DQB1-mismatched donors are available, additional testing of DRB3/4/5 may help to lower risks. Most recently, mismatching for the non-classical class I gene, MICA, has been shown to impact GVHD and survival in some [6,7], but not other, studies [8]. …”

Section: Patient-donor Matchingmentioning

confidence: 99%

Which factors influence the development of GVHD in HLA-matched or mismatched transplants?

Petersdorf

2017

Best Practice & Research Clinical Haematology

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The sheer diversity of HLA alleles makes the probability of finding matched unrelated donors for patients requiring hematopoietic cell transplantation (HCT) a complex situation. New evidence suggests that mismatching at certain HLA loci may provide a greater benefit in terms of graft-versus-leukemia effect than other mismatches when HLA-matched donors are not available. This review summarizes the current understanding of HLA matching requirements for unrelated donor HCT.

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“…The principal relevance of the NKG2D pathway for HSCT is further emphasized by studies showing an effect of the genotype of the NKG2D ligand RAET1L (64) and NKG2D itself (65) on the survival of patients. Moreover, matching for MICA alleles (66–69) and specifically for the MICA-129 polymorphism (70) is beneficial in HSCT. The huge effect of MICA-129 matching appears hardly explainable solely by the avoidance of a potential minor histocompatibility antigen.…”

Section: Mica-129met/val Disease Associations In View Of Biological Fmentioning

confidence: 99%

Impact of the MICA-129Met/Val Dimorphism on NKG2D-Mediated Biological Functions and Disease Risks

et al. 2016

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The major histocompatibility complex (MHC) class I chain-related A (MICA) is the most polymorphic non-classical MHC class I gene in humans. It encodes a ligand for NKG2D (NK group 2, member D), an activating natural killer (NK) receptor that is expressed mainly on NK cells and CD8+ T cells. The single-nucleotide polymorphism (SNP) rs1051792 causing a valine (Val) to methionine (Met) exchange at position 129 of the MICA protein is of specific interest. It separates MICA into isoforms that bind NKG2D with high (Met) and low affinities (Val). Therefore, this SNP has been investigated for associations with infections, autoimmune diseases, and cancer. Here, we systematically review these studies and analyze them in view of new data on the functional consequences of this polymorphism. It has been shown recently that the MICA-129Met variant elicits a stronger NKG2D signaling, resulting in more degranulation and IFN-γ production in NK cells and in a faster costimulation of CD8+ T cells than the MICA-129Val variant. However, the MICA-129Met isoform also downregulates NKG2D more efficiently than the MICA-129Val isoform. This downregulation impairs NKG2D-mediated functions at high expression intensities of the MICA-Met variant. These features of the MICA-129Met/Val dimorphism need to be considered when interpreting disease association studies. Particularly, in the field of hematopoietic stem cell transplantation, they help to explain the associations of the SNP with outcome including graft-versus-host disease and relapse of malignancy. Implications for future disease association studies of the MICA-129Met/Val dimorphism are discussed.

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Matching for the MICA-129 polymorphism is beneficial in unrelated hematopoietic stem cell transplantation

Abstract: Key Points MICA-129 matching improves survival in uHSCT. MICA-129 mismatches were observed in 6.7% of all transplant patients.

Cited by 41 publications

References 40 publications

Natural Killer Group 2, Member D/NKG2D Ligands in Hematopoietic Cell Transplantation

Natural Killer Group 2, Member D/NKG2D Ligands in Hematopoietic Cell Transplantation

Which factors influence the development of GVHD in HLA-matched or mismatched transplants?

Impact of the MICA-129Met/Val Dimorphism on NKG2D-Mediated Biological Functions and Disease Risks

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