The impact of KIR2DS4 gene on clinical outcome after hematopoietic stem cell transplantation

Kamenarić, Marija Burek; Janković, Katarina Štingl; Grubić, Zorana; Seiwerth, Ranka Serventi; Maskalan, Marija; Nemet, Damir; Mikulić, Mirta; Žunec, Renata

doi:10.1016/j.humimm.2016.11.010

Cited by 14 publications

(15 citation statements)

References 25 publications

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“…It has been suggested that intracellular retention of KIR may aid NK cell licencing and/or ensure minimal inhibition of NK cell activity . Other studies have assessed the influence of KIR2DS4*030101 in donors, although data is conflicting …”

Section: Kir and Haemopoietic Progenitor Cell Transplantationmentioning

confidence: 99%

Killer‐cell immunoglobulin‐like receptor assessment algorithms in haemopoietic progenitor cell transplantation: current perspectives and future opportunities

Wright

2020

HLA

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Natural killer cells preferentially target and kill malignant and virally infected cells. Both these properties present compelling clinical utility in the field of haemopoietic progenitor cell transplantation (HPCT), potentially promoting a graft vs leukaemia effect in the absence of graft vs host disease and protecting against cytomegalovirus activation. Killer Ig-like receptors (KIR) play a central role in the cytotoxic action of natural killer cells, providing opportunity for improving transplantation outcomes by prioritising potential donors with optimal characteristics. Numerous algorithms for assessing KIR gene content as part of HPCT donor selection protocols exist, but no single model has been found to be universally applicable in all transplant centres. This review summarises several of the predominant strategies in KIR assessment algorithms, discussing their basic scientific principles, clinical utility and benefits to posttransplant outcomes. Finally, the review will consider how future donor selection protocols could develop towards unifying the concepts of KIR proteomics and genetics for optimising patient care.

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Section: Kir and Haemopoietic Progenitor Cell Transplantationmentioning

confidence: 99%

Killer‐cell immunoglobulin‐like receptor assessment algorithms in haemopoietic progenitor cell transplantation: current perspectives and future opportunities

Wright

2020

HLA

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“…16 The median absolute nucleated cell count was 11.4 × 10 8 /kg (range: 9.6-14.8 × 10 8 /kg), and the median dose of CD34 + cells was 4.9 × 10 6 /kg (range: 3.5-6.4 × 10 6 /kg). The median time to neutrophil recovery was 12 days (range: [8][9][10][11][12][13][14][15][16][17][18][19] (full-length 2DS4); if the sample hit for probe 145 as well as probe 234, the sample would be typed as 2DS4*deletion Ex.5.…”

Section: Patient Donor and Transplant Characteristicsmentioning

confidence: 99%

The impact of donor full‐length KIR2DS4 in the development of acute and chronic GVHD after unrelated allogeneic HSCT

Luo

et al. 2020

Pediatric Transplantation

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Background Killer Ig‐like receptor 2DS4 (KIR2DS4) is the most prevalent activating killer Ig‐like receptor gene. It is divergent and encodes either full‐length or deleted allele variants. The studies of donor killer KIR2DS4 in unrelated allogeneic hematopoietic stem cell transplantations were limited. Methods KIR and HLA genotyping were determined in 75 pairs of Chinese pediatric hematologic malignancy patients. Results Among the 75 donor‐recipient pairs, 77.3% (58/75) of the donors were positive for full‐length KIR2DS4 and 22.7% (17/75) were negative. Patients who had donors positive for full‐length KIR2DS4 had higher cumulative incidence of aGVHD than patients whose donor negative for full‐length KIR2DS4 (86.2% versus 76.5%, P = .038). Multivariate analysis showed full‐length KIR2DS4 was the significant factor for I‐IV aGVHD (HR = 2.166, 95% CI: 1.01‐4.26, P = .025). Subgroup analysis showed that AML and CML patients who received donors negative for full‐length KIR2DS4 have a higher cumulative incidences of cGVHD (75% vs 62%, P = .008). There were no significant effects of full‐length KIR2DS4 on overall survival (P = .13), relapse‐free survival (P = .14), CMV reactivation (P = .52), and relapse (HR = 0.38, 95% CI: 0.09‐1.6, P = .1875). Conclusions Our findings indicated a significant correlation of donor full‐length KIR2DS4 on aGVHD and cGVHD. These results suggested that combining KIR and HLA genotyping may help make a better sense of transplants in these patients.

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“…Among related donor HSCT recipients, patients whose donors had 1-2 KIR2DS4 full alleles had a significantly lower OS as compared to patients whose donors had a KIR2DS4 del allele or no KIR2DS4 allele (HR = 7.9; p = 0.016). In the MUD group, HSCT from a KIR2DS4 full donor was associated with a higher risk for GVHD (HR = 8.2; p = 0.012) and non-relapse mortality (NRM) than from a donor with KIR2DS4 del allele or no KIR2DS4 allele [101]. Another study in 75 Chinese patients who underwent T-cell deplete MUD HSCT showed significantly higher risk of acute GVHD (RR 9.0, p = 0.01) in patients whose donors were homozygous for KIR2DS4 full allele [102].…”

Section: Impact Of Activating Nk-cell Receptors and Kir Haplotypes Onmentioning

confidence: 99%

NK cell therapy for hematologic malignancies

et al. 2018

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Natural killer (NK) cells are part of the innate immune system and represent the first line of defense against infections and tumors. In contrast to T cells, NK cells do not require prior antigen sensitization to induce cytotoxicity and do not cause graft-versus-host disease. These, along with other advantages, make NK cells an attractive candidate for adoptive cellular therapy. Herein, we describe the mechanisms of NK cell cytotoxicity, which is governed by an intricate balance between various activating and inhibitory receptors, including the killer cell immunoglobulin-like receptors (KIRs). We illustrate the advantages of NK alloreactivity as demonstrated in various types of hematopoietic stem cell transplants (HSCT), such as haploidentical, human leukocyte antigen-matched related or unrelated donor and umbilical cord blood transplant. We elaborate on different models used to predict NK cell alloreactivity in these studies, which are either based on the absence of the ligands for inhibitory KIRs, presence of activating NK cell receptors and KIR genes content in donors, or a combination of these. We will review clinical studies demonstrating anti-tumor efficacy of NK cells used either as a stand-alone immunotherapy or as an adjunct to HSCT and novel genetic engineering strategies to improve the anti-tumor activity of NK cells.

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The impact of KIR2DS4 gene on clinical outcome after hematopoietic stem cell transplantation

Cited by 14 publications

References 25 publications

Killer‐cell immunoglobulin‐like receptor assessment algorithms in haemopoietic progenitor cell transplantation: current perspectives and future opportunities

Killer‐cell immunoglobulin‐like receptor assessment algorithms in haemopoietic progenitor cell transplantation: current perspectives and future opportunities

The impact of donor full‐length KIR2DS4 in the development of acute and chronic GVHD after unrelated allogeneic HSCT

NK cell therapy for hematologic malignancies

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