FIPA : étude clinique et génétique à l'Hôpital "King Edward Memorial", Bombay (Mumbai) Inde
; Daly, Adrian ; CASTERMANS, Emilie et al
in Annales d'Endocrinologie (2013, October), 74Detailed reference viewed: 11 (1 ULg)
Impact of bone marrow-derived mesenchymal stromal cells on experimental xenogeneic graft-versus-host disease
; Belle, Ludovic ; LECHANTEUR, Chantal et al
in Cytotherapy (2013), 15(3), 267-279
Background aims. Graft-versus-host disease (GVHD) is a life-threatening complication of allogeneic hematopoietic cell transplantation caused by donor T cells reacting against host tissues. Previous ... [more ▼]
Background aims. Graft-versus-host disease (GVHD) is a life-threatening complication of allogeneic hematopoietic cell transplantation caused by donor T cells reacting against host tissues. Previous studies have suggested that mesenchymal stromal cells (MSCs) could exert potent immunosuppressive effects. Methods. The ability of human bone marrow derived MSCs to prevent xenogeneic GVHD in non-obese diabetic/severe combined immunodeficient (NOD/SCID) mice and in NOD/SCID/interleukin-2Rg(null) (NSG) mice transplanted with human peripheral blood mononuclear cells (PBMCs) was assessed. Results. Injection of 200 106 human PBMCs intraperitoneally (IP) into sub-lethally (3.0 Gy) irradiated NOD/SCID mice also given anti-asialo GM1 antibodies IP 1 day prior and 8 days after transplantation induced lethal xenogeneic GVHD in all tested mice. Co-injection of 2 106 MSCs IP on day 0 did not prevent lethal xenogeneic GVHD induced by injection of human PBMCs. Similarly, injection of 30 106 human PBMCs IP into sub-lethally (2.5 Gy) irradiated NSG mice induced a lethal xenogeneic GVHD in all tested mice. Injection of 3 106 MSCs IP on days 0, 7, 14 and 21 did not prevent lethal xenogeneic GVHD induced by injection of human PBMCs. Conclusions. Injection of MSCs did not prevent xenogeneic GVHD in these two humanized mice models. [less ▲]Detailed reference viewed: 44 (18 ULg)
Existe-t-il une predisposition genetique aux addictions ?
CASTERMANS, Emilie ; GAILLEZ, Stephanie ; BOURS, Vincent
in Revue Médicale de Liège (2013), 68(5-6), 226-32
Is free will the rule in front of drugs, alcohol or gambling? Would interindividual genetic variations influence our behaviour to such a point that addiction susceptibility would be enhanced or decreased ... [more ▼]
Is free will the rule in front of drugs, alcohol or gambling? Would interindividual genetic variations influence our behaviour to such a point that addiction susceptibility would be enhanced or decreased? Addiction predisposition is a complex trait, involving numerous predisposition genes and also environment. Heritability of this trait is 50%, meaning a similar contribution of genes and environment in the setting of this trait. Some genes of the dopaminergic system and some others specific for various drugs metabolism have been associated to addictions. The growth of those findings into promising pilot treatments seems a good future coming in. [less ▲]Detailed reference viewed: 17 (4 ULg)
Ary Hydrocarbon receptor interacting protein (AIP) on somatotroph adenomas : a molecular target for somatostatin analogues ?
; ; et al
in Endocrine abstracts - May 2012, volume 29 (2012, May)Detailed reference viewed: 23 (0 ULg)
Bone marrow-derived mesenchymal stromal cells failed to prevent experimental xenogeneic graft-versus-host disease
; ; Belle, Ludovic et al
Poster (2012)Detailed reference viewed: 25 (8 ULg)
Characterization of CD8+ T-cell response in acute and resolved hepatitis A virus infection.
; ; et al
in Journal of Hepatology (2011), 54(2), 201-208
Abstract BACKGROUND & AIMS: In contrast to the infection with other hepatotropic viruses, hepatitis A virus (HAV) always causes acute self-limited hepatitis, although the role for virus-specific CD8 T ... [more ▼]
Abstract BACKGROUND & AIMS: In contrast to the infection with other hepatotropic viruses, hepatitis A virus (HAV) always causes acute self-limited hepatitis, although the role for virus-specific CD8 T cells in viral containment is unclear. Herein, we analyzed the T cell response in patients with acute hepatitis by utilizing a set of overlapping peptides and predicted HLA-A2 binders from the polyprotein. METHODS: A set of 11 predicted peptides from the HAV polyprotein, identified as potential binders, were synthesized. Peripheral blood mononuclear cells (PBMCs) from patients were tested for IFNγ secretion after stimulation with these peptides and ex vivo with HLA-A2 tetramers. Phenotyping was carried out by staining with the activation marker CD38 and the memory marker CD127. RESULTS: Eight out of 11 predicted HLA-A2 binders showed a high binding affinity and five of them were recognized by CD8+ T cells from patients with hepatitis A. There were significant differences in the magnitude of the responses to these five peptides. One was reproducibly immunodominant and the only one detectable ex vivo by tetramer staining of CD8+ T cells. These cells have an activated phenotype (CD38hi CD127lo) during acute infection. Three additional epitopes were identified in HLA-A2 negative patients, most likely representing epitopes restricted by other HLA-class I-alleles (HLA-A11, B35, B40). CONCLUSIONS: Patients with acute hepatitis A have a strong multi-specific T cell response detected by ICS. With the tetramer carrying the dominant HLA-A2 epitope, HAV-specific and activated CD8+ T cells could be detected ex vivo. This first description of the HAV specific CTL-epitopes will allow future studies on strength, breadth, and kinetics of the T-cell response in hepatitis A. [less ▲]Detailed reference viewed: 9 (0 ULg)
Thymic recovery after allogeneic hematopoietic cell transplantation with nonmyeloablative conditioning is limited to patients younger than 60 years of age
CASTERMANS, Emilie ; Hannon, Muriel ; et al
in Haematologica (2011), 96(2)Detailed reference viewed: 24 (15 ULg)
Parallel detection of antigen-specific T-cell responses by multidimensional encoding of peptide-Major Histocompatibility Complexes
; ; et al
in Nature Methods (2009), 6((7)), 520-526
Abstract The use of fluorescently labeled MHC multimers has become an essential technique for the analysis of disease- and therapy-induced T cell immunity. While classical MHC multimer analyses are well ... [more ▼]
Abstract The use of fluorescently labeled MHC multimers has become an essential technique for the analysis of disease- and therapy-induced T cell immunity. While classical MHC multimer analyses are well-suited for the detection of immune responses against a few epitopes, limitations on patient sample size preclude a comprehensive analysis of T cell immunity. To address this issue, we have developed a combinatorial encoding strategy that allows the parallel detection of a multitude of different T cell populations within a single sample. Detection of antigen-specific T cells from peripheral blood by combinatorial encoding is as efficient as detection with conventional PE labeled multimers, but results in a significantly increased sensitivity, and most importantly, allows comprehensive screens to be performed on patient material. Proof of principle for the feasibility of large-scale screening of patient material was obtained by analysis of HLA-A3 restricted T cell responses against known and potential melanoma-associated antigens in peripheral blood from melanoma patients. 2 [less ▲]Detailed reference viewed: 75 (8 ULg)
What Is The Role For Regulatory T-Cells After Nonmyeloablative Conditioning?
; CASTERMANS, Emilie ; et al
in Biology of Blood & Marrow Transplantation (2009, February), 15(2), 122-123Detailed reference viewed: 11 (3 ULg)
Reconstitution du système immunitaire après allogreffe de cellules souches hématopoïétiques
Castermans, Emilie ; Hannon, Muriel ; Drion, Pierre et al
in Revue Médicale de Liège (2009), 64(S1), 2-8
Allogeneic hematopoietic stem cell transplantation (alloHCT) is frequently used as treatment for patients with hematological malignancies. Its efficacy depends in part on the destruction of recipient ... [more ▼]
Allogeneic hematopoietic stem cell transplantation (alloHCT) is frequently used as treatment for patients with hematological malignancies. Its efficacy depends in part on the destruction of recipient tumors cells by donor immune cells contained in the graft (graft-versus-tumor effects), underlying the interest of stydying donor immune recovery after alloHCT. Further, donor immune cells play an important role in the prevention and treatment of infections after allHCT, and are the cause of graft-versus-host disease (GVHD). This article reviews the mechanisms of immune recovery after allogeneic hematopoietic cell transplantation (alloHCT), as well as techniques currently used to monitor immune function following allHCT. [less ▲]Detailed reference viewed: 116 (29 ULg)
What is the Role for Regulatory T-Cells after Nonmyeloablative conditioning
; CASTERMANS, Emilie ; et al
in Biology of Blood & Marrow Transplantation (2008, February), 14(2), 136-137Detailed reference viewed: 12 (2 ULg)
Evidence for neo-generation of T cells by the thymus after non-myeloablative conditioning.
Castermans, Emilie ; Baron, Frédéric ; Willems, Evelyne et al
in Haematologica (2008), 93(2), 240-7
BACKGROUND: Background and objective. We investigated immune recovery in 50 patients given either unmanipulated or CD8-depleted allogeneic peripheral blood stem cells after non-myeloablative conditioning ... [more ▼]
BACKGROUND: Background and objective. We investigated immune recovery in 50 patients given either unmanipulated or CD8-depleted allogeneic peripheral blood stem cells after non-myeloablative conditioning. DESIGN AND METHODS: Fifty patients were randomized to receive either CD8-depleted (n=22) or non-manipulated (n=28) peripheral blood stem cells. The median patients age was 57 (range 36-69) years. The conditioning regimen consisted of 2 Gy total body irradiation with or without added fludarabine. Twenty patients received grafts from related donors, 14 from 10/10 HLA-allele matched unrelated donors, and 16 from HLA-mismatched unrelated donors. Graft-versus-host disease pro-phylaxis consisted of mycophenolate mofetil and cyclosporine. Immune recovery during the first year after hematopoietic cell transplantation was assessed by flow cytometry phenotyping, analyses of the diversity of the TCRBV repertoire, and quantification of signal-joint T-cell receptor excision circles (sjTREC). RESULTS: CD8-depletion of the graft reduced the recovery of CD8(+) T-cell counts in the first 6 months following transplantation (p<0.0001) but had no significant impact on the restoration of other T-cell subsets. Both sjTREC concentration and CD3(+) T-cell counts increased significantly between day 100 and 365 (p=0.010 and p=0.0488, respectively) demonstrating neo-production of T cells by the thymus. Factors associated with high sjTREC concentration 1 year after transplantation included an HLA-matched unrelated donor (p=0.029), a high content of T cells in the graft (p=0.002), and the absence of chronic graft-versus-host disease (p<0.0001). CONCLUSIONS: Our data suggest that while immune recovery is mainly driven by peripheral expansion of the graft-contained mature T cells during the first months after non-myeloablative transplantation, T-cell neo-generation by the thymus plays an important role in long term immune reconstitution in transplanted patients. [less ▲]Detailed reference viewed: 159 (85 ULg)
Evaluation clinique de la fonction du thymus.
Castermans, Emilie ; Morrhaye, Gabriel ; et al
in Revue Médicale de Liège (2007), 62(11), 675-8
The essential role of the thymus is to install an extremely diverse repertoire of T lymphocytes that are self-tolerant and competent against non-self, as well as to generate self-antigen specific ... [more ▼]
The essential role of the thymus is to install an extremely diverse repertoire of T lymphocytes that are self-tolerant and competent against non-self, as well as to generate self-antigen specific regulatory T cells (Treg) able to inactivate in periphery self-reactive T cells having escaped the thymic censorship. Although indirect, techniques of medical imaging and phenotyping of peripheral T cells may help in the investigation of thymic function. Nowadays however, thymopoiesis is better evaluated through quantification by PCR of T-cell receptor excision circles (TREC) generated by intrathymic random recombination of the gene segments coding for the variable parts of the T-cell receptor for antigen (TCR). The TREC methodology is very valuable in the circumstances not associated with intense proliferation or apoptosis of peripheral T lymphocytes. [less ▲]Detailed reference viewed: 88 (12 ULg)
Evaluation de la thymopoiese: applications cliniques.
Castermans, Emilie ; Morrhaye, Gabriel ; et al
in Revue Médicale de Liège (2007), 62(12), 725-9
In the precedent article, we have described how T-cell generation in the thymus (thymopoiesis) may be currently evaluated through quantification by PCR of T-cell receptor excision circles (TREC) generated ... [more ▼]
In the precedent article, we have described how T-cell generation in the thymus (thymopoiesis) may be currently evaluated through quantification by PCR of T-cell receptor excision circles (TREC) generated by intrathymic random recombination of the gene segments coding for variable parts of T-cell receptor for antigen (TCR). In hematology, TREC methodology helps in a better understanding of immune reconstitution after graft of hematopoietic stem cells: first there is a proliferation of mature T cells present in the graft, then a differentiation of naive T cells. In geriatrics, the homeostasis of the peripheral T-cell repertoire is maintained through proliferation of peripheral memory T cells rather than through thymic generation of naive T cells. In addition, TREC quantification constitutes a novel major tool for deciphering the tight control of thymopoiesis by the neuroendocrine system. [less ▲]Detailed reference viewed: 57 (11 ULg)
Raloxifene-induced myeloma cell apoptosis: a study of nuclear factor-kappaB inhibition and gene expression signature.
Olivier, Sabine ; Close, Pierre ; Castermans, Emilie et al
in Molecular Pharmacology (2006), 69(5), 1615-1623
Because multiple myeloma remains associated with a poor prognosis, novel drugs targeting specific signaling pathways are needed. The efficacy of selective estrogen receptor modulators for the treatment of ... [more ▼]
Because multiple myeloma remains associated with a poor prognosis, novel drugs targeting specific signaling pathways are needed. The efficacy of selective estrogen receptor modulators for the treatment of multiple myeloma is not well documented. In the present report, we studied the antitumor activity of raloxifene, a selective estrogen receptor modulator, on multiple myeloma cell lines. Raloxifene effects were assessed by tetrazolium salt reduction assay, cell cycle analysis, and Western blotting. Mobility shift assay, immunoprecipitation, chromatin immunoprecipitation assay, and gene expression profiling were performed to characterize the mechanisms of raloxifene-induced activity. Indeed, raloxifene, as well as tamoxifen, decreased JJN-3 and U266 myeloma cell viability and induced caspase-dependent apoptosis. Raloxifene and tamoxifen also increased the cytotoxic response to vincristine and arsenic trioxide. Moreover, raloxifene inhibited constitutive nuclear factor-kappaB (NF-kappaB) activity in myeloma cells by removing p65 from its binding sites through estrogen receptor alpha interaction with p65. It is noteworthy that microarray analysis showed that raloxifene treatment decreased the expression of known NF-kappaB-regulated genes involved in myeloma cell survival and myeloma-induced bone lesions (e.g., c-myc, mip-1alpha, hgf, pac1,...) and induced the expression of a subset of genes regulating cellular cycle (e.g., p21, gadd34, cyclin G2,...). In conclusion, raloxifene induces myeloma cell cycle arrest and apoptosis partly through NF-kappaB-dependent mechanisms. These findings also provide a transcriptional profile of raloxifene treatment on multiple myeloma cells, offering the framework for future studies of selective estrogen receptor modulators therapy in multiple myeloma. [less ▲]Detailed reference viewed: 69 (20 ULg)
Nonmyeloablative stem cell transplantation with CD8-depleted or unmalipulated peripheral blood stem cells: a prospective randomized trial.
WILLEMS, Evelyne ; CASTERMANS, Emilie ; Baron, Frédéric et al
in Belgian Hematological Society (2006)Detailed reference viewed: 12 (0 ULg)
Despite inhibition of hematopoietic progenitor cell growth in vitro, the tyrosine kinase inhibitor imatinib does not impair engraftment of human CD133+ cells into NOD/SCIDbeta2mNull mice.
Pirson, Laurence ; Baron, Frédéric ; Meuris, Nathalie et al
in Stem Cells (2006), 24(7), 1814-21
There is potential interest for combining allogeneic hematopoietic cell transplantation (HCT), and particularly allogeneic HCT with a nonmyeloablative regimen, to the tyrosine kinase inhibitor imatinib ... [more ▼]
There is potential interest for combining allogeneic hematopoietic cell transplantation (HCT), and particularly allogeneic HCT with a nonmyeloablative regimen, to the tyrosine kinase inhibitor imatinib (Glivec; Novartis, Basel, Switzerland, http://www.novartis.com) in order to maximize anti-leukemic activity against Philadelphia chromosome-positive leukemias. However, because imatinib inhibits c-kit, the stem cell factor receptor, it could interfere with bone marrow engraftment. In this study, we examined the impact of imatinib on normal progenitor cell function. Imatinib decreased the colony-forming capacity of mobilized peripheral blood human CD133(+) cells but not that of long-term culture-initiating cells. Imatinib also decreased the proliferation of cytokine-stimulated CD133(+) cells but did not induce apoptosis of these cells. Expression of very late antigen (VLA)-4, VLA-5, and CXCR4 of CD133(+) cells was not modified by imatinib, but imatinib decreased the ability of CD133(+) cells to migrate. Finally, imatinib did not decrease engraftment of CD133(+) cells into irradiated nonobese diabetic/severe combined immunodeficient/beta2m(null) mice conditioned with 3 or 1 Gy total body irradiation. In summary, our results suggest that, despite inhibition of hematopoietic progenitor cell growth in vitro, imatinib does not interfere with hematopoietic stem cell engraftment. [less ▲]Detailed reference viewed: 66 (33 ULg)
Immune reconstitution after CD8-depleted or unmanipulated peripheral blood stem cells transplantation with nonmyeloablative conditioning
Castermans, Emilie ; Baron, Frédéric ; Willems, Evelyne et al
in Acta Clinica Belgica (2006), 61(2), 113Detailed reference viewed: 25 (9 ULg)
SERMs-induced myeloma cell apoptosis: A study of NF-kappa B inhibition and gene expression signature
Olivier, Sabine ; Close, Patricia ; Castermans, Emilie et al
in Journal of Bone and Mineral Research (2005, September), 20(9, Suppl. 1), 213Detailed reference viewed: 24 (4 ULg)