The many faces of regulatory T cells

"Regulatory T cell" is a generic name that globally covers a number of T cell subsets that can mediate suppression of cellular immunity in some in vitro and in vivo experiments. One of these subsets becomes differentiated in the thymus and is chiefly characterized by the expression of the Foxp3 transcription factor. It is postulated that these natural T reg cells recognize self peptides complexed to self MHC with moderate affinity and are thought to contribute to the preservation of self tolerance beyond negative thymic selection against high affinity anti-self T cell receptors. This is illustrated by mice and human patients devoid of these cells, who develop aggressive and extended autoimmune lymphoid infiltrates in different organs. CD4+ T cells producing anti-inflammatory cytokines also down regulate cellular immunity although they might cooperate with certain humoral responses. The rapidly progressing knowledge on the surface phenotype, and the transcriptome/proteome of these cells is offering plenty of opportunities for immune intervention. Deactivation or depletion of Treg cells might lead to increased immunity against viral chronicity or malignant diseases, whereas adoptive transfer or agonist stimulations of their function might have a role in the treatment of organ specific autoimmunity. However, abundant experimental discrepancies and uncertainties challenge and complicate this promising field for translational research

El nombre de "células T reguladoras" define a una subpoblación de células T con capacidad supresora tanto in vitro como in vivo. Parte de esa subpoblación tiene origen tímico y se caracteriza por la expresión del factor de transcripción Foxp3; estas células son conocidas como “T reguladoras naturales” y contribuyen a preservar la tolerancia a lo propio. Se ha descrito que dichas células reconocen péptidos propios con afinidad intermedia tras un proceso de selección negativa en el timo donde previamente se habrían eliminado los clones de células T con alta afinidad por péptidos propios. Tanto en el hombre como en modelos animales, la ausencia de esta población de células T se traduce en fenómenos agresivos de autoinmunidad con un importante infiltrado linfocitario en diferentes órganos. Las células T CD4+ producen citocinas anti-inflamatorias que también colaboran en la supresión de la inmunidad celular. Los últimos hallazgos sobre el fenotipo de las células T reguladoras, así como en su genoma, están haciendo posible el desarrollo de múltiples estrategias para la inmunoterapia. La inactivación o depleción de las Treg podría aumentar la respuesta inmune frente a enfermedades virales crónicas, mientras que la transferencia adoptiva o la estimulación de estas células mediante agonistas sería de gran ayuda para el tratamiento de enfermedades autoinmunes. Sin embargo, la existencia de ciertas discrepancias en los modelos experimentales, hace que aún queden puntos por resolver antes de iniciar la inmunoterapia en clínica

[Nonalcoholic steatohepatitis, the enigma of bad progression]. / Esteatohepatitis no alcohólica, el enigma de una mala evolucion.

Still, very little is known about the precise pathogenetic mechanisms, the triggering events and in particular, the evolution and treatment of nonalcoholic steatohepatitis (NASH). It is part of the broad spectrum of nonalcoholic fatty liver diseases (NAFLDs). Mainly, it has been reported as a benign disease, associated with metabolic disorders commonly occurrence en the general population. Nevertheless, the syndrome can lead to cirrhosis, liver failure or hepatocellular carcinoma, requiring liver transplantation. We present one patient with diagnosis of NASH, who was treated initially for overweight, HTA and hyperlipaemia with incompleted response and who showed a quickly progress to cirrhosis but no cause of liver decompensated disease could be identified. Currently she is at end-stage waiting a liver transplantation. Controlled and multicentric studies with the same definition of NASH and the study end-points are needed, and will provide information about diagnosis features and novel therapies to early management of the disease.

Esteatohepatitis no alcohólica, el enigma de una mala evolucion / Nonalcoholic steatohepatitis, the enigma of bad progress

Hasta ahora poco se sabe acerca de la patogenia, los desencadenantes y en particular de la evolución y terapia de la esteatohepatitis no alcohólica (EHNA). Incluída en el amplio espectro de enfermedades del hígado graso no alcohólicas. Se ha considerado una enfermedad mayoritariamente benigna y asociada a alteraciones metabólicas muy prevalentes en la población general. Sin embargo no es raro que progrese a cirrosis, insuficiencia hepática o hepatocarcinoma que precise transplante hepático. Presentamos el caso de una paciente que diagnosticamos de EHNA, al inicio con respuesta parcial y tardía al tratamiento para el sobrepeso, la HTA y la hiperlipidemia, pero con una evolución rápida a cirrosis hepática sin identificarse ningún factor desencadenante. Actualmente es candidata a transplante hepático.Son necesarios estudios multicéntricos y controlados, con la misma definición de EHNA y objetivos comunes que aportarán información sobre datos diagnósticos y nuevas terapias para el manejo precoz de la enfermedad

Still, very little is known about the precise pathogenetic mechanisms, the triggering events and in particular, the evolution and treatment of non-alcoholic steatohepatitis (NASH). It is part of the broad spectrum of nonalcoholic fatty liver diseases ( NAFLDs). Mainly, it has been reported as a benign disease, asociated with metabolic disorders commonly occurrence en the general population. Nevertheless, the syndrome can lead to cirrhosis, liver failure or hepatocellular carcinoma, requiring liver transplantation. We present one pacient with diagnosis of NASH, who was treated initially for overweight, HTA and hyperlipaemia with incompleted response and who showed a quickly progress to cirrosis but no cause of liver descompensated disease could be identified. Currently she is at end-stage waitting a liver transplantation. Controlled and multicentric studies with the same definition of NASH and the study end-points are needed, and will provide informationabout diagnosis features and novel therapies to early management of the disease

Fabry's disease: long-term study of a family.

Fabry's disease is the second most prevalent lysosomal storage disorder after Gaucher's disease. It occurs as the result of a deficit in the alpha-galactosidase A enzyme. The gene coding for it is located on the long arm of the X chromosome (Xq22.1). This deficit causes the gradual accumulation of a glycosphingolipid. The main substance accumulated is globotriaosylceramide (Gb3). This accumulation leads to pain and angiokeratomas, and to cardiac, cerebral, and vascular involvement as the disease progresses. The treatment of Fabry's disease has so far only been symptomatic; however, new advances have now made it possible to prescribe alpha-galactosidase replacement therapy, which not only improves symptoms, but also enhances these patients' quality of life and lowers mortality. In this paper we review the status of Fabry's disease and we report the follow-up of a family with Fabry's disease, with some members receiving replacement therapy with alpha-galactosidase A and demonstrating good progress.

[Treatment of malignant pheochromocytoma with 131I MIBG: a long survival]. / Feocromocitoma maligno tratado con MIBG I131:una larga supervivencia.

131I-metaiodobenzylguanidine (131I-MIBG) is a structural analogue of adrenal hormone norepinephrine employed to localise tumours derived of neural crest and in the treatment of malignant pheochromocytomas. Although the number of patients is low, in the revised literature there are objective remissions and reduction of hormonal activity, with symptomatic answers. However, the reduction of size of tumour only has been described in some times and hardly ever in the presence of osseous metastasis. We present one patient diagnoses of malignant pheochromocytoma with osseous metastasis, who was treated with 131I-MIBG. It was administrated a total dose of 1,800 mCu, with an excellent tolerance and short adverse symptoms. There were a partial tumour response and a complete hormonal response, with a survival of 30 years after the diagnoses.

Feocromocitoma maligno tratado con MIBG I131: una larga supervivencia / Treatment of malignant pheochromocytoma with 131I-MIBG: a long survival

La metaiodobenzilguanidina marcada con I131 (MIBG I131) es un analogo estructural de la hormona adrenérgica norepinefrina que se utiliza para la localización de tumores derivados de la cresta neural y para el tratamiento de feocromocitomas malignos. Aunque el número de pacientes tratados es pequeño, en la literatura revisada se dispone de datos acerca de la inducción de remisiones objetivas y de la reducción de la actividad hormonal, consiguiendo respuestas sintomáticas. Sin embargo, la reducción del tamaño tumoral sólo se ha descrito en algunas ocasiones y casi nunca en presencia de metástasis óseas. Presentamos el caso de un paciente diagnosticado de feocromocitoma maligno, con afectación ósea, que recibió tratamiento con MIBG I131.Se administró una dosis total aproximada de 1.800 mCu, con una buena tolerancia y escasos efectos secundarios. Hubo una respuesta tumoral parcial y una respuesta hormonal completa, con una supervivencia de 30 años tras el diagnóstico (AU)