Search results for: Itxaso Portero Sainz

Authors: Federico Herrera, Valle Gomez García de Soria, Itxaso Portero Sainz, Carlos Fernández Arandojo, Mercedes Royg, Ana Marcos Jimenez, Anna Kreutzman, Cecilia MuñozCalleja

Abstract:

Introduction: Graft-versus-host disease (GVHD) still remains the major complication associated with allogeneic stem cell transplantation (SCT). The pathogenesis involves migration of donor naïve T-cells into recipient secondary lymphoid organs. Two molecules are important in this process: CD62L and CCR7, which are characteristically expressed in naïve/central memory T-cells. With this background, we aimed to study the influence of CCR7 and CD62L on donor lymphocytes in the development and severity of GVHD. Material and methods: This single center study included 98 donor-recipient pairs. Samples were collected prospectively from the apheresis product and phenotyped by flow cytometry. CCR7 and CD62L expression in CD4+ and CD8+ T-cells were compared between patients who developed acute (n=40) or chronic GVHD (n=33) and those who did not (n=38). Results: The patients who developed acute GVHD were transplanted with a higher percentage of CCR7+CD4+ T-cells (p = 0.05) compared to the no GVHD group. These results were confirmed when these patients were divided in degrees according to the severity of the disease; the more severe disease, the higher percentage of CCR7+CD4+ T-cells. Conversely, chronic GVHD patients received a higher percentage of CCR7+CD8+ T-cells (p=0.02) in comparison to those who did not develop the complication. These data were also confirmed when patients were subdivided in degrees of the disease severity. A multivariable analysis confirmed that percentage of CCR7+CD4+ T-cells is a predictive factor of acute GVHD whereas the percentage of CCR7+CD8+ T-cells is a predictive factor of chronic GVHD. In vitro functional assays (migration and activation assays) supported the idea of CCR7+ T-cells were involved in the development of GVHD. As low levels of CD62L expression were detected in all apheresis products, we tested the hypothesis that CD62L was shed during apheresis procedure. Comparing CD62L surface levels in T-cells from the same donor immediately before collecting the apheresis product, and the final apheresis product we found that this process down-regulated CD62L in both CD4+ and CD8+ T cells (p=0.008). Interestingly, when CD62L levels were analysed in days 30 or 60 after engraftment, they recovered to baseline (p=0.008). However, to investigate the relation between CD62L expression and the development of GVHD in the recipient samples after the engraftment, no differences were observed comparing patients with GVHD to those who did not develop the disease. Discussion: Our prospective study indicates that the CCR7+ T-cells from the donor, which include naïve and central memory T-cells, contain the alloreactive cells with a high ability to mediate GVHD (in the case of both migration and activation). Therefore we suggest that the proportion and functional properties of CCR7+CD4+ and CCR7+CD8+ T-cells in the apheresis could act as a predictive biomarker to both acute and chronic GVHD respectively. Importantly, our study precludes that CD62L is lost in the apheresis and therefore it is not a reliable biomarker for the development of GVHD.

Keywords: CCR7, CD62L, GVHD, SCT

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Authors: Juan José Mesas, Luis Sainz

Abstract:

The motivation for the development of this paper lies in the need for energy networks to reduce losses, improve performance, optimize their operation and try to benefit from the interconnection capacity with other networks enabled for other energy carriers. These interconnections generate interdependencies between some energy networks and others, which requires suitable models and methods for their analysis. Traditionally, the modeling and study of energy networks have been carried out independently for each energy carrier. Thus, there are well-established models and methods for the steady-state analysis of electrical networks, gas networks, and thermal networks separately. What is intended is to extend and combine them adequately to be able to face in an integrated way the steady-state analysis of networks with multiple energy carriers. Firstly, the added value of multi-energy networks, their operation, and the basic principles that characterize them are explained. In addition, two current aspects of great relevance are exposed: the storage technologies and the coupling elements used to interconnect one energy network with another. Secondly, the characteristic equations of the different energy networks necessary to carry out the steady-state analysis are detailed. The electrical network, the natural gas network, and the thermal network of heat and cold are considered in this paper. After the presentation of the equations, a particular case of the steady-state analysis of a specific multi-energy network is studied. This network is represented graphically, the interconnections between the different energy carriers are described, their technical data are exposed and the equations that have previously been presented theoretically are formulated and developed. Finally, the two iterative numerical resolution methods considered in this paper are presented, as well as the resolution procedure and the results obtained. The pros and cons of the application of both methods are explained. It is verified that the results obtained for the electrical network (voltages in modulus and angle), the natural gas network (pressures), and the thermal network (mass flows and temperatures) are correct since they comply with the distribution, operation, consumption and technical characteristics of the multi-energy network under study.

Keywords: coupling elements, energy carriers, multi-energy networks, steady-state analysis

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