Activating killer immunoglobulin‐like receptor incompatibilities enhance graft‐versus‐host disease and affect survival after allogeneic hematopoietic stem cell transplantation

Giebel, Sebastian; Nowak, Izabela; Dziaczkowska, Joanna; Czerw, Tomasz; Wojnar, Jerzy; Krawczyk-Kuliś, Małgorzata; Hołowiecki, Jerzy; Holowiecka-Goral, Aleksandra; Markiewicz, Mirosław; Kopera, Małgorzata; Karolczyk, Agnieszka; Kyrcz‐Krzemień, Sławomira; Kuśnierczyk, Piotr

doi:10.1111/j.1600-0609.2009.01280.x

Cited by 39 publications

(27 citation statements)

References 41 publications

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“…Ninety-six patients treated with allogeneic hematopoietic stem cell transplant in the Department of Hematology and Bone Marrow Transplantation of the Silesian Medical University in Katowice because of leukemia (53 women, 43men; mean age, 33.3±10.9 years; including acute lymphoblastic leukemia, ALL, 22 patients, 11 women, 11 men; mean age, 27.4±9.7; acute myeloid leukemia, AML, 40 patients, 26 women, 14 men; mean age, 36.9±12.1; chronic myeloid leukemia, CML, 34 patients, 16 women, 18 men; mean age, 33.1 years) were described elsewhere [25].…”

Section: Methodsmentioning

confidence: 99%

Does the KIR2DS5 Gene Protect from Some Human Diseases?

et al. 2010

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Background KIR2DS5 gene encodes an activating natural killer cell receptor whose ligand is not known. It was recently reported to affect the outcome of hematopoietic stem cell transplantation.Methodology/Principal FindingsIn our studies on KIR2DS5 gene associations with human diseases, we compared the frequencies of this gene in patients and relevant controls. Typing for KIR2DS5 gene was performed by either individual or multiplex polymerase chain reactions which, when compared in the same samples, gave concordant results. We noted an apparently protective effect of KIR2DS5 gene presence in several clinical conditions, but not in others. Namely, this effect was observed in ankylosing spondylitis (p = 0.003, odds ratio [OR] = 0.47, confidence interval [CI] = 0.28–0.79), endometriosis (p = 0.03, OR = 0.25, CI = 0.07–0.82) and acute rejection of kidney graft (p = 0.0056, OR = 0.44, CI = 0.24–0.80), but not in non-small-cell lung carcinoma, rheumatoid arthritis, spontaneous abortion, or leukemia (all p>0.05). In addition, the simultaneous presence of KIR2DS5 gene and HLA-C C1 allotype exhibited an even stronger protective effect on ankylosing spondylitis (p = 0.0003, OR = 0.35, CI = 0.19–0.65), whereas a lack of KIR2DS5 and the presence of the HLA-C C2 allotype was associated with ankylosing spondylitis (p = 0.0017, OR = 1.92, CI = 1.28–2.89), whereas a lack of KIR2DS5 and presence of C1 allotype was associated with rheumatoid arthritis (p = 0.005, OR = 1.47, CI = 1.13–1.92). The presence of both KIR2DS5 and C1 seemed to protect from acute kidney graft rejection (p = 0.017, OR = 0.47, CI = 0.25–0.89), whereas lack of KIR2DS5 and presence of C2 seemed to favor rejection (p = 0.0015, OR = 2.13, CI = 1.34–3.37).Conclusions/SignificanceOur results suggest that KIR2DS5 may protect from endometriosis, ankylosing spondylitis, and acute rejection of kidney graft.

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Section: Methodsmentioning

confidence: 99%

Does the KIR2DS5 Gene Protect from Some Human Diseases?

et al. 2010

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“…28 The following monoclonal antibodies were used for this part of the study: CD45-FITC, CD14-PE, CD3-FITC, CD4-PE, CD8-PE, CD19-PE (Beckman Dickinson, San Jose, CA, USA).…”

Section: Analysis Of Lymphocyte Subpopulations In Parallel To Nk Celmentioning

confidence: 99%

Sequential recovery of NK cell receptor repertoire after allogeneic hematopoietic SCT

Giebel

Dziaczkowska

Czerw

et al. 2010

Bone Marrow Transplant

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“…Despite the establishment that outcome was impacted by KIRs in a majority of cases, contradictory results prevailed. The enhancement or depreciation of survival ensued from donor/recipient incompatibilities and existence of activating KIRs (30).…”

Section: Discussionmentioning

confidence: 99%

“…They established that a negative patient and a positive donor resulted in a higher risk of acute (KIR2DS1) and chronic (KIR2DS3) GVHD including relapse (KIR2DS5) (30).…”

Section: Discussionmentioning

confidence: 99%

The impact of donor and recipient KIR genes and KIR ligands on the occurrence of acute graft-versus-host disease and graft survival after HLA-identical sibling hematopoietic stem cell transplantation

2018

Turk J Med Sci

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IntroductionAllogeneic hematopoietic stem cell transplantation (allo-HSCT) is the definitive choice for treatment of highrisk hematologic malignancies, even in advanced stages (1,2). There is evidence that allogeneic HLA-matched transplantation for patients with lymphoblastic and myeloblastic leukemia is more effective than autogeneic transplantation, because allo-HSCT may induce the graftversus-leukemia (GVL) effect (3,4). The potential benefit of the GVL effect relies on the elimination of residual malignant cells through immunological antitumor effects, induced by alloreactive T and natural killer (NK) cells, which leads to a lower relapse rate in allo-HSCT patients with hematologic malignancies (3,5,6). Despite all the advantages of allo-HSCT, there are still some complications that limit the success of this important procedure, including the development of graft-versushost disease (GVHD) (7). Alloreactive cells in the graft are widely considered to mediate both the GVL effect and GVHD (8).Acute GVHD, a major source of morbidity in HSCT, is mediated by donor allogeneic cytotoxic T cells against host tissues and leads to the recruitment of other effector cells including NK cells (9,10). The pathophysiology of acute GVHD has been described as a three-phase phenomenon: activation of donor-derived T cells, effector phase through Background/aim: After allogeneic hematopoietic stem cell transplantation (allo-HSCT), donor natural killer (NK) cells trigger alloreactions against potential recipient cells by their killer immunoglobulin-like receptors (KIRs). This study investigated whether KIR/HLA genotypes and KIR haplotypes of donors and recipients exhibit a critical function in the prevalence of acute graft-versus-host disease (aGVHD) and persistence of the graft after HLA-identical sibling allo-HSCT for patients with hematological malignancies. Materials and methods:We studied KIR and HLA genotypes in 115 related donors and recipients (56 patients with AML and 59 patients with ALL) who had received allo-HSCT from HLA-matched sibling donors. We evaluated 17 KIR genes and some alleles, including their ligands, using the PCR-SSP assay.Results: KIR gene frequency results between donors and recipients showed that donors had more activating KIR than their recipients. Chi-square comparison of KIR genotype frequencies in donors versus recipients revealed a significant difference (P < 0.001). We found a survival association between the donor lacking and the recipient having group B KIR haplotypes, although this was not statistically significant. Conclusion:This study suggests that we could exploit NK cell alloreactivity as a part of the optimization of donor selection and potential immunotherapeutic regimens to help facilitate good engraftment and reduce the risk of aGVHD incidence after allo-HSCT.

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Activating killer immunoglobulin‐like receptor incompatibilities enhance graft‐versus‐host disease and affect survival after allogeneic hematopoietic stem cell transplantation

Cited by 39 publications

References 41 publications

Does the KIR2DS5 Gene Protect from Some Human Diseases?

Does the KIR2DS5 Gene Protect from Some Human Diseases?

Sequential recovery of NK cell receptor repertoire after allogeneic hematopoietic SCT

The impact of donor and recipient KIR genes and KIR ligands on the occurrence of acute graft-versus-host disease and graft survival after HLA-identical sibling hematopoietic stem cell transplantation

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