Interactions between killer immunoglobulin‐like receptors and their human leucocyte antigen Class I ligands influence the outcome of unrelated haematopoietic stem cell transplantation for thalassaemia: a novel predictive algorithm

Littera, Roberto; Orrù, Nicola; Caocci, Giovanni; Sanna, Marco; Mulargia, M; Piras, E; Vacca, Adriana; Giardini, Claudio; Orofino, Maria Grazia; Visani, Giuseppe; Bertaina, Alice; Giorgiani, Giovanna; Locatelli, Franco; Carcassi, Carlo; Nasa, Giorgio La

doi:10.1111/j.1365-2141.2011.08923.x

Cited by 14 publications

(14 citation statements)

References 37 publications

(60 reference statements)

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“…A second possibility is that CD8+ T cells are involved in loss of tolerance within secondary lymphoid organs, functioning as an early source of IFNγ that promotes Th1 skewing of CD4+ T cells. The effects of donor HLA class I may also reflect the contribution of a class I-dependent NK cell mechanism [35], [36]. While many studies of the influence of specific donor HLA class I alleles were conducted on populations with little overlap with the donors in the present study, donor HLA C401 has been identified as promoting severe GVHD in both humans and the BLT GVHD model, suggesting that the BLT GVHD model may be predictive of specific genetic or environmental factors that contribute to the development of human GVHD [11].…”

Section: Discussionmentioning

confidence: 99%

Graft versus Host Disease in the Bone Marrow, Liver and Thymus Humanized Mouse Model

et al. 2012

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Mice bearing a “humanized” immune system are valuable tools to experimentally manipulate human cells in vivo and facilitate disease models not normally possible in laboratory animals. Here we describe a form of GVHD that develops in NOD/SCID mice reconstituted with human fetal bone marrow, liver and thymus (NS BLT mice). The skin, lungs, gastrointestinal tract and parotid glands are affected with progressive inflammation and sclerosis. Although all mice showed involvement of at least one organ site, the incidence of overt clinical disease was approximately 35% by 22 weeks after reconstitution. The use of hosts lacking the IL2 common gamma chain (NOD/SCID/γc−/−) delayed the onset of disease, but ultimately did not affect incidence. Genetic analysis revealed that particular donor HLA class I alleles influenced the risk for the development of GVHD. At a cellular level, GVHD is associated with the infiltration of human CD4+ T cells into the skin and a shift towards Th1 cytokine production. GVHD also induced a mixed M1/M2 polarization phenotype in a dermal murine CD11b+, MHC class II+ macrophage population. The presence of xenogenic GVHD in BLT mice both presents a major obstacle in the use of humanized mice and an opportunity to conduct preclinical studies on GVHD in a humanized model.

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Section: Discussionmentioning

confidence: 99%

Graft versus Host Disease in the Bone Marrow, Liver and Thymus Humanized Mouse Model

et al. 2012

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“…On a large series of patients with HSCT from HLA matched, unrelated donors, Cooley et al [28] have shown that patients having KIR2DS2 and KIR2DL2 together with absence of KIR2DL3 in donors, are associated with significantly better prognosis. Only recently, another research group has confirmed these findings in a group of patients with thalassemia, again transplanted from unrelated, HLA matched donors [29].…”

Section: Discussionmentioning

confidence: 86%

Association of Killer Cell Immunoglobulin-Like Receptor Genes with the Graft versus Host Disease after Related Haematopoietic Stem Cell Transplantation in Patients with Haematological Malignancies from Republic of Macedonia

et al. 2012

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Aim: The aim of this study was to examine the gene frequencies of 16 KIR genes and pseudogenes and KIR genotypes in Macedonian patients with transplanted bone marrow and their sibling donors in treatment of haematological malignancy, and to analyse eventual association of the gene content with the occurrence of a graft versus host disease (GVHD). Material and Methods:The study was performed on 24 patients and their HLA-matched sibling donors. Results:Comparison of KIR gene frequencies between the total 24 donors and healthy Macedonians reveals statistically significant difference for KIR2DS1 (F= 0.481 in the controls group, and 0.76 in the patients group, p=0.004). This significance is even higher when the frequency of KIR2DS1 in controls is compared with the frequency in donors from pairs with GVHD (F= 0.923, P= 0.002). Another significant difference was observed for the frequency of the full-length allele of KIR2DS4*001-002, present in 25.2% of the control individuals, but in as much as 81.8% of the recipients of haematopoietic stem cell (P=0.0005). We did not see any statistically significant difference in distribution of the C1/C1, C1/C2 and C2/C2 groups among GVHD pairs. Conclusion:Our results address the difference between the haematopoietic stem cell transplantation settings with sibling and unrelated donors and suggest that the KIR2DS4*001/002 might be a predisposing factor for severe GVHD in sibling HSCT.

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“…For example, HSC homing is influenced by several molecules involved in inflammatory and other signaling pathways of innate immune response 47,48…”

Section: Bone Marrow Homingmentioning

confidence: 99%

Bone Marrow Homing and Engraftment Defects of Human Hematopoietic Stem and Progenitor Cells

Caocci

Nasa

2017

Mediterr J Hematol Infect Dis

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Homing of hematopoietic stem cells (HSC) to their microenvironment niches in the bone marrow is a complex process with a critical role in repopulation of the bone marrow after transplantation. This active process allows for migration of HSC from peripheral blood and their successful anchoring in bone marrow before proliferation. The process of engraftment starts with the onset of proliferation and must, therefore, be functionally dissociated from the former process. In this overview, we analyze the characteristics of stem cells (SCs) with particular emphasis on their plasticity and ability to find their way home to the bone marrow. We also address the problem of graft failure which remains a significant contributor to morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). Within this context, we discuss non-malignant and malignant hematological disorders treated with reduced-intensity conditioning regimens or grafts from human leukocyte antigen (HLA)-mismatched donors.

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Interactions between killer immunoglobulin‐like receptors and their human leucocyte antigen Class I ligands influence the outcome of unrelated haematopoietic stem cell transplantation for thalassaemia: a novel predictive algorithm

Cited by 14 publications

References 37 publications

Graft versus Host Disease in the Bone Marrow, Liver and Thymus Humanized Mouse Model

Graft versus Host Disease in the Bone Marrow, Liver and Thymus Humanized Mouse Model

Association of Killer Cell Immunoglobulin-Like Receptor Genes with the Graft versus Host Disease after Related Haematopoietic Stem Cell Transplantation in Patients with Haematological Malignancies from Republic of Macedonia

Bone Marrow Homing and Engraftment Defects of Human Hematopoietic Stem and Progenitor Cells

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