KIR2DL2/S2 and KIR2DS5 in alcoholic cirrhotic patients undergoing liver transplantation.

INTRODUCTION: The molecular mechanisms underlying alcoholic liver fibrosis and cirrhosis are not completely understood. Hepatic fibrosis involves the interplay of diverse cells and factors, including hepatic stellate cells (HSCs), Kupffer, NK cells, and T-lymphocyte subsets. Killer-cell immunoglobulin-like receptors (KIR) are membrane receptors involved in mediation between NK and activated HSCs, regulating NK cell function through their interaction with HLA-I molecules. The aim of this study was to analyse the genetic association between KIR genes and the susceptibility to or protection from alcoholic cirrhosis (AC) in a cohort of male AC patients undergoing liver transplantation (LT) with and without concomitant viral infections. MATERIAL AND METHODS: KIR genotyping was performed in nuclear DNA extracted from 281 AC patients and compared with 319 male controls. RESULTS: Significant differences between total AC patients and healthy controls were only found in the case of KIR2DL2 and KIR2DS5. KIR2DL2 was significantly underrepresented in non-viral AC patients (52.6% vs. 63.3%; p = 0.015), while patients heterozygous for KIR2DL2 were also underrepresented in the non-viral AC group compared with controls (p = 0.034). KIR2DS5 was overrepresented in this group compared with healthy controls (p = 0.002). All these observations were only evident in AC patients older than 54 years old. CONCLUSIONS: Our data suggest a contrary effect of KIR2DL2 and KIR2DS5 in AC patients older than 54 years, in whom the presence of KIR2DL2 appears to be protective against AC, whereas the presence of KIR2DS5 seems to promote the fibrotic process, particularly in patients with no associated viral infection.

The predictive value of soluble major histocompatibility complex class I chain-related molecule A (MICA) levels on heart allograft rejection.

BACKGROUND: Recently the presence of a soluble form of major histocompatibility complex class I chain-related molecule A (sMICA) has been detected in the sera of patients with tumors. Shedding of sMICA by tumor cells downregulates NKG2D-mediated antitumor immunity. The aim of this investigation was to study the possible involvement of sMICA in the allograft acceptance after heart transplantation (HTX). METHODS: We monitored the levels of sMICA by specific enzyme-linked immunosorbent assay (ELISA) in a total of 146 serum samples obtained from 34 heart transplantation patients followed up during the first year post-HTX. RESULTS: The persistence of sMICA expression was correlated with the clinical evolution of these patients. sMICA was detected in the serum of 21 of 34 patients (61.70%) between 15 and 20 days after implantation and was practically absent in pretransplant serum samples. Twenty of these 21 patients (95.24%) with sMICA did not experience episodes of severe rejection during this period (P = 0.0001), whereas sMICA was practically absent in patients with manifestations of severe acute rejection. The longitudinal study of these patients revealed that the presence of sMICA was consistently maintained in 75% of the patients with good graft status during the period of observation. CONCLUSION: This has led us to believe that the presence of levels of sMICA during the first year post-HTX may contribute to allograft acceptance. Additionally, functional studies indicate that sMICA downregulates NKG2D surface expression, which may lead to a functional impairment of cell-mediated cytolysis. These data suggest a significant correlation between the presence of sMICA and a lower incidence of rejection.

La información y el consentimiento: la nueva dimensión de la medicina actual / Information and consent: the new dimension of medicine today

Introducción. El ejercicio de la medicina ha evolucionado en los últimos años desde el patrón paternalista clásico hacia un sistema basado en el respeto por las preferencias del paciente: el autonomismo, que consagra la libertad de elección frente a las distintas alternativas planteadas en el seno de las relaciones asistenciales, con cuatro elementos esenciales en su desarrollo: la información recibida, la libertad de elección, la capacidad para decidir y la propia decisión. Para ejercer este derecho a su autonomía, el paciente tiene que disponer de una información adecuada, que debe ser veraz, suficiente y comprensible, según se establece tanto en el Código de Deontología Médica (obligación ética) como en el Convenio de Oviedo y la Ley 41/2004 (obligación legal). Desarrollo. Sobre este planteamiento teórico se revisan las especificaciones legales relacionadas con el derecho a la información y la obligatoriedad de informar, las particularidades del proceso de toma de decisiones, así como las desviaciones que se producen en la práctica diaria tanto por parte de los profesionales como de los pacientes. Conclusiones. El proceso de toma de decisiones debe estar libre de interferencias tanto internas como externas, principalmente persuasiones, manipulaciones y coacciones, y siendo el paciente competente, su decisión autónoma debe respetarse, al margen de que podamos o no estar de acuerdo con ella (AU)

Introduction. Medical praxis has evolved in recent years from the classical paternalistic pattern towards a system based on respect for the patient’s preferences: that is to say, autonomism, which gives priority to freedom of choice above the other possible alternatives that can be considered in health care relationships. This approach involves four essential elements: the information received, freedom of choice, the capacity to decide and the actual decision. To exercise this right to their autonomy, patients must have access to suitable information, which must be truthful, sufficient and understandable, according to the provisions of both the Code of Medical Deontology (ethical obligation) and the Oviedo Agreement and Law 41/2001 (legal obligation). DEVELOPMENT. On the basis of this theoretical approach we also review the legal specifications concerning the right to information and the obligation to inform, the particularities of the decision-making process, as well as the deviations that are produced in daily practice by both professionals and patients. CONCLUSIONS. The decision-making process must be free from both internal and external interferences, especially persuasion, manipulation and coercion, and, provided the patient is competent, his or her autonomous decision must be respected, regardless of whether we agree with it or not (AU)

Lack of association between the -403G/A promoter polymorphism in the human CCL5/RANTES chemokine gene in liver transplant outcome.

Chemokines play a major role in the inflammatory and immune responses that mediate allograft outcome. CCL5/RANTES expansion chemokine is potent eosinophil, monocyte, basophils and lymphocyte chemoattractant and has recently been studied in transplantation with discrepant results, but systemic concentrations have been correlated to liver graft survival and incidence of rejection. Recent studies revealed that a functional mutation at -403 in the promoter may have a significance for inflammatory and infectious immune responses. Our objective was to investigate CCL5/RANTES promoter polymorphism in rejection and graft survival in liver transplant. We examined the CCL5/RANTES polymorphism in a series of 218 liver transplants and 101 healthy Caucasian subjects. CCL5/RANTES genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). After comparing recipients (with acute rejection episodes versus without rejection) with the control population, we found no significant deviation in the distribution of the alleles or genotypes of CCL5/RANTES dimorphism in any comparison (P > 0.05). Indeed, 5 years allograft survival was 61.3% in recipients with the GG genotype against 58.8% in recipients with the GA and AA genotypes. These differences were also not statistically significant. In conclusion, human CCL5/RANTES gene promoter polymorphism does not seem to influence acute rejection development and allograft survival in liver recipients.