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H Watier

Publications and source records attributed to H Watier.

At least 19 recordsLinked to original sources
PubMed2005

Intralesional therapy with anti-CD20 monoclonal antibody rituximab: local and systemic efficacy in primary cutaneous B-cell lymphoma.

Rituximab (MabThera, Roche) is a chimeric monoclonal antibody directed against the CD20 antigen. Its efficacy and safety were first demonstrated in the treatment of systemic B-cell lymphomas. We report the use of intralesional injections of rituximab into some but not all cutaneous lesions in a patient with multiple primary cutaneous follicular centre B-cell lymphoma. This treatment resulted in tumour regression, even of the lesions that had not been injected. We therefore hypothesize that there is systemic diffusion of rituximab from injected sites despite the low doses injected locally, or the induction of a specific antitumour immune response acting systemically.

Adult↗
PubMed2004

Relationship between calcineurin inhibition and plasma endothelin concentrations in cyclosporine-A-treated kidney transplant patients.

OBJECTIVE: The inter-individual variability of cyclosporine (CsA) pharmacokinetics is well known. However, there is obviously also an inter-individual pharmacodynamic variability, which might be explored by the measurement of biomarkers of CsA effects. METHODS: In 11 renal transplant patients, blood CsA concentrations, calcineurin inhibition in peripheral blood mononuclear cells and endothelin plasma concentrations were measured over a 4-h period after CsA intake. RESULTS: Mean plasma endothelin concentrations were higher than those of healthy subjects (3.66+/-0.46 pg ml(-1) versus 3.15+/-0.40 pg ml(-1), P<0.01) but were not related to CsA dose or blood concentrations. There was a linear relationship between calcineurin inhibition at t (0) and mean endothelin concentrations (r (2)=0.51, P<0.05). Patients with gingival hypertrophy had higher mean endothelin concentrations than patients without this complication (4.0 pg ml(-1) versus 3.4 pg ml(-1), P<0.01), although CsA doses and concentrations were not different between these two groups. CONCLUSION: We observed a correlation between calcineurin inhibition and endothelin concentrations. Endothelin plasma concentrations is a biomarker of CsA effect, which may provide more information than CsA blood concentrations.

Adult↗
PubMed2004

Association between polymorphism in IgG Fc receptor IIIa coding gene and biological response to infliximab in Crohn's disease.

AIM: To test the hypothesis of an association between polymorphism in FCGR3A (the gene coding for FcgammaRIIIa, which is expressed on macrophages and natural killer cells, is involved in antibody-dependent cell-mediated cytotoxicity and has recently been associated with a positive response to rituximab, a recombinant immunoglobulin G1 antibody used in non-Hodgkin's lymphomas) and response to infliximab in Crohn's disease. METHODS: FCGR3A-158 polymorphism was determined using an allele-specific polymerase chain reaction assay in 200 Crohn's disease patients who had received infliximab for either refractory luminal (n = 142) or fistulizing (n = 58) Crohn's disease. Clinical and biological responses (according to C-reactive protein levels) were assessed in 200 and 145 patients, respectively. RESULTS: There were 82.9% clinical responders in V/V patients vs. 72.7% in V/F and F/F patients (N.S.). Globally, the decrease in C-reactive protein was significantly higher in V/V patients than in F carriers (P = 0.0078). A biological response was observed in 100% of V/V patients, compared with 69.8% of F carriers (P = 0.0002; relative risk, 1.43; 95% confidence interval, 1.27-1.61). In the sub-group of patients with elevated C-reactive protein before treatment, the multivariate analysis selected the use of immunosuppressive drugs and FCGR3A genotype as independent factors influencing the clinical response to infliximab (P = 0.003). CONCLUSION: Crohn's disease patients with FCGR3A-158 V/V genotype have a better biological and, possibly, clinical response to infliximab.

Adult↗
PubMed2001

Association between the SDF1-3'A allele and high levels of CD34(+) progenitor cells mobilized into peripheral blood in humans.

Some patients unexpectedly fail to mobilize sufficient numbers of haematopoietic progenitor cells (HPCs) into the peripheral blood for autologous transplantation. Considering the important role of the chemokine stromal cell-derived factor 1 (SDF-1) in HPC homing, we investigated a possible relationship between SDF1 gene polymorphism and HPC mobilization capacity in 63 patients with malignancy. Some 67% of the good mobilizers (> or = 50 CD34(+) cells/microl) and only 36% of the intermediate/poor mobilizers were SDF1-3'A allele carriers (P = 0.032). In multivariate analysis, the presence of the SDF1-3'A allele was the only factor predictive of good CD34(+) cell mobilization (P = 0.025). This is the first report showing the involvement of genetic factors for HPC mobilization in humans and suggests a significant role for SDF-1 in this process.

Adult↗
PubMed2000

Development of an ex vivo model of pig kidney perfused with human lymphocytes. Analysis of xenogeneic cellular reactions.

BACKGROUND: Because of the explosive nature and the extremely rapid process of hyperacute rejection (HAR), significant infiltration of the xenograft by immunocompetent cells is not observed, and the role and the mechanism of action of cell-mediated rejection in discordant xenografts are therefore still under discussion. METHOD: We developed an experimental approach using pig kidneys perfused with human peripheral blood lymphocytes (PBL) in which the immunologic barrier of hyperacute rejection was excluded and which mimics the in vivo situation. RESULTS: PBL retention in the kidney was evaluated at 20-minute intervals for 3 hours. Retention increased from 30% to 80% with the time of perfusion and was specific because significantly fewer syngeneic lymphocytes were retained. Phenotype analysis of recovered PBL showed a significant decrease in natural killer (NK) cells. Immunohistochemical studies revealed the presence of NK cells and T lymphocytes in the glomerular and interstitial tubular structures of the kidney. Functional studies showed a progressive cessation of diuresis and augmentation of renal vascular resistance when the kidney was perfused with PBL. Electron microscopy examinations of kidney sections perfused with PBL showed swollen endothelial zones, suggesting alterations to and damage of the endothelium. CONCLUSIONS: This system provides a valuable model for the study of early discordant xenogeneic cellular rejection and demonstrates the predominance of xenograft infiltration by NK cells.

Animals↗
PubMed2000

[Anti-pig xenogeneic response by human CD4+ T-lymphocytes].

When considering the hypothesis of xenotransplantation, and if it becomes possible to control hyperacute and delayed vascular rejection, the recognition of porcine graft by human T CD4+ lymphocytes could still constitute a very important barrier. The direct recognition of porcine MHC class II molecules (SLA-DR and SLA-DQ) by human TCR has been demonstrated in vitro. It is accompanied by a proliferative lymphocytic response, as co-stimulatory molecules are able to interact across the species barrier. In vivo, this type of recognition only applies to porcine cells with antigen-presenting functions, mainly the graft dendritic cells which emigrate into the recipient lymphoid organs. The other recognition pathway is indirect, whereby the recipient dendritic cells capture porcine xenoantigens in the graft, then process and present them to the lymphocytes in the lymphoid organs. This indirect pathway can be shown in vitro by utilizing porcine MHC class II-negative endothelial cells. In this model, human purified T CD4+ lymphocyte proliferation is tightly dependent on the presence of human antigen-presenting cells and their HLA class II molecules. As the xenogenic peptides all differ from self peptides, the indirect T-cell response will be very strong and probably difficult to control.

Animals↗
PubMed1999

Trophoblast cell line resistance to NK lysis mainly involves an HLA class I-independent mechanism.

The lack of classical HLA molecules on trophoblast prevents allorecognition by maternal T lymphocytes, but poses the problem of susceptibility to NK lysis. Expression of the nonclassical class I molecule, HLA-G, on cytotrophoblast may provide the protective effect. However, the class I-negative syncytiotrophoblast escapes NK lysis by maternal PBL. In addition, while HLA-G-expressing transfectants of LCL.721.221 cells are protected from lymphokine-activated killer lysis, extravillous cytotrophoblast cells and HLA-G-expressing choriocarcinoma cells (CC) are not. The aim of this work was therefore to clarify the role of HLA class I expression on trophoblast cell resistance to NK lysis and on their susceptibility to lymphokine-activated killer lysis. Our results showed that both JAR (HLA class I-negative) and JEG-3 (HLA-G- and HLA-Cw4-positive) cells were resistant to NK lysis by PBL and were equally lysed by IL-2-stimulated PBL isolated from a given donor. In agreement, down-regulating HLA class I expression on JEG-3 cells by acid treatment, masking these molecules or the putative HLA-G (or HLA-E) receptor CD94/NKG2 and the CD158a/p58.1 NKR with mAbs, and inducing self class I molecule expression on JAR cells did not affect NK or LAK lysis of CC. These results demonstrate that the resistance of CC to NK lysis mainly involves an HLA class I-independent mechanism(s). In addition, we show that the expression of a classical class I target molecule (HLA-B7) on JAR cells is insufficient to induce lysis by allospecific polyclonal CTL.

Antigens, CD↗
PubMed1998

Human T lymphocyte proliferative response to resting porcine endothelial cells results from an HLA-restricted, IL-10-sensitive, indirect presentation pathway but also depends on endothelial-specific costimulatory factors.

To investigate the mechanisms of cellular rejection in pig-to-human xenotransplantation, the proliferation of different human purified lymphocyte subpopulations in response to swine leukocyte Ag class II-negative porcine aortic endothelial cells (PAEC) was measured in the presence or absence of human autologous adherent cells (huAPC). CD8+ lymphocytes proliferated moderately in the absence of huAPC, and the immune response was slightly increased when huAPC were added. CD56+ lymphocytes failed to proliferate in response to PAEC whether huAPC were present or not. CD4+ lymphocytes alone did not proliferate in response to PAEC, but a strong proliferative response was observed in the presence of metabolically active huAPC. This response was totally abolished by mAbs directed against HLA class II molecules or by pretreatment of huAPC by human IL-10. Even in the presence of huAPC, CD4+ lymphocytes failed to respond to fixed PAEC or to PAEC-lysates, suggesting that PAEC must be viable to support lymphocyte proliferation. Finally, none of the nonendothelial porcine adherent cells tested was able to induce human lymphocyte proliferation, despite the fact that they also provided a large set of xenogeneic peptides. Our results show that the indirect presentation pathway of xenoantigens by huAPC to CD4+ lymphocytes is crucial in the response to porcine endothelial cells, and that IL-10 could be of therapeutic interest to prevent human lymphocyte activation by this pathway. Furthermore, we demonstrated that stimulatory signals specifically provided by endothelial cells are also necessary for this huAPC-restricted proliferative response.

Animals↗
PubMed1998

Human allogeneic lymphocytes trigger endothelial cell tissue factor expression by a tumor necrosis factor-dependent pathway.

Lymphocyte adhesion to endothelial cells and the extravascular deposition of fibrin are 2 important processes during pathologic situations such as allograft rejection. Tissue factor (TF) expression was therefore measured on human umbilical vein endothelial cells (HUVECs) after coculture with allogeneic lymphocytes (PBLs) by a factor Xa generation assay. When cocultured with PBLs, HUVECs expressed strong procoagulant activity related to the TF/factor VII-dependent pathway, which was enhanced when endothelial cells were treated with interferon-gamma (IFN-gamma). The highest TF activity was measured when 10(5) lymphocytes were incubated with 10(4) HUVECs (ratio 10: 1) for 4 hours, a time-dependent course similar to that obtained with tumor necrosis factor-alpha (TNF-alpha), and direct contact between the 2 cell types was necessary. PBL-induced TF activity was inhibited by cycloheximide or actinomycin D, indicating active protein synthesis that was confirmed by the increase in TF mRNA detected by reverse transcription-polymerase chain reaction. It was then demonstrated that 1 of the primary signaling pathways leading to endothelial cell TF expression was a rapid initial interaction between membrane TNF expressed on PBLs and the 75-kd TNF receptor, with subsequent involvement of platelet-activating factor and P-selectin. Finally, we showed that the transduction of external signals involving the activation of protein kinase C and protein tyrosine kinases also contributed to the regulation of TF expression.

Cells, Cultured↗
PubMed1998

Removal of primate xenoreactive natural antibodies by extracorporeal perfusion of pig kidneys and livers.

Organ perfusion is one of the possible strategies to attenuate rejection of discordant xenografts by reducing the levels of the recipient's xenoreactive natural antibodies (XNA). Its efficacy in terms of XNA removal was studied in models of primate blood or plasma perfusion through porcine kidneys or livers, with special attention to haematological consequences and potential side-effects. We first perfused the blood of rhesus monkeys through pig kidneys and livers, and demonstrated that the perfusion of a pig liver resulted in higher XNA adsorption (72 +/- 13%) than the perfusion of a pig kidney (51 +/- 25%). However, when we normalized for the weight of the perfused organs and for levels of natural antibodies in individual monkeys, livers adsorbed less antibody (1.4 +/- 0.9 U antibody/g) than kidneys (7.2 +/- 7 U antibody/g). Histological signs of rejection were observed in perfused kidneys, but not in perfused livers. A major drawback of the perfusion of blood through livers was a considerable decrease in the primates' haemoglobin and platelet levels. To avoid this, we developed a plasma liver perfusion device. This method allowed a significant improvement in the haemodynamic state of primates and was particularly effective in preventing anaemia. Moreover, plasma liver perfusion was as effective as blood liver perfusion to remove natural antibodies and, resulted in a marked decrease in their functional activity as assessed by complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC). The level of other plasma proteins was not significantly affected, apart from a dilution effect. After xenoperfusion a strong antibody response was evidenced by ELISA, CDC and ADCC between days 7 and 14 and then decreased progressively. We conclude that the separation of blood to allow the perfusion of plasma through a pig organ is safer than the perfusion of unseparated blood and is associated with efficient natural antibody removal. However, organ perfusion is limited by a rebound in antibody levels after a few days, and thus will have to be associated with anti-B cell immunosuppressive therapy for long-term or repeated applications.

Animals↗
PubMed1997

[Role of the endothelium in leukocyte trafficking].

Vascular endothelium controls leukocyte recirculation and recruitment, receiving messages from underlying tissues and transforming them into informations quickly read by the passaging leukocytes. These messages induce adhesive interactions between leukocytes and endothelium via adhesion molecules. Multiple receptor-ligand pairs function in 4 steps: initial tethering and rolling of leukocytes; leukocyte triggering by chemotactic factors; arrest and strong adhesion to endothelium; and ultimately transendothelial migration (diapedesis).

Cell Adhesion↗