RESUMEN
There is an ongoing need to develop strategic combinations of therapeutic agents to prevent type 1 diabetes (T1D) or to preserve islet ß-cell mass in new-onset disease. Although clinical trials using candidate therapeutics are commonly based on preclinical studies, concern is growing regarding the reproducibility as well as the potential clinical translation of reported results using animal models of human disorders. In response, the National Institutes of Health Immune Tolerance Network and JDRF established a multicenter consortium of academic institutions designed to assess the efficacy and intergroup reproducibility of clinically applicable immunotherapies for reversing new-onset disease in the NOD mouse model of T1D. Predicated on prior studies, this consortium conducted coordinated, prospective studies, using joint standard operating procedures, fixed criteria for study entry, and common reagents, to optimize combined anti-CD3 treatment plus interleukin-1 (IL-1) blockade to reverse new-onset disease in NOD mice. We did not find that IL-1 blockade with anti-IL-1ß monoclonal antibody or IL-1trap provided additional benefit for reversing new-onset disease compared with anti-CD3 treatment alone. These results demonstrate the value of larger, multicenter preclinical studies for vetting and prioritizing therapeutics for future clinical use.
Asunto(s)
Anticuerpos Monoclonales/administración & dosificación , Enfermedades Autoinmunes/tratamiento farmacológico , Complejo CD3/química , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Células Secretoras de Insulina/efectos de los fármacos , Insulina/metabolismo , Interleucina-1beta/antagonistas & inhibidores , Animales , Anticuerpos Monoclonales/química , Anticuerpos Monoclonales/uso terapéutico , Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/metabolismo , Investigación Biomédica/métodos , Complejo CD3/metabolismo , Diabetes Mellitus Tipo 1/inmunología , Diabetes Mellitus Tipo 1/metabolismo , Esquema de Medicación , Quimioterapia Combinada , Femenino , Fragmentos Fab de Inmunoglobulinas/administración & dosificación , Fragmentos Fab de Inmunoglobulinas/química , Fragmentos Fab de Inmunoglobulinas/uso terapéutico , Inmunoterapia/métodos , Secreción de Insulina , Células Secretoras de Insulina/inmunología , Células Secretoras de Insulina/metabolismo , Proteína Accesoria del Receptor de Interleucina-1/antagonistas & inhibidores , Proteína Accesoria del Receptor de Interleucina-1/metabolismo , Interleucina-1beta/metabolismo , Ratones Endogámicos NOD , Estudios Multicéntricos como Asunto , Proyectos Piloto , Receptores Tipo I de Interleucina-1/antagonistas & inhibidores , Receptores Tipo I de Interleucina-1/metabolismo , Proteínas Recombinantes de Fusión/uso terapéutico , Reproducibilidad de los Resultados , Proyectos de Investigación , Organismos Libres de Patógenos Específicos , Estados UnidosRESUMEN
Serology has been used for HLA typing for many decades; however, serological typing of histocompatibility class II molecules depends on the adequade expression of these molecules on the surface of B lymphocytes, the availability of viable cells and a complete set on antisera. HLA typing at the genomic level has supplanted these pitfalls. The utilization of restriction fragment length polymorphism (RFLP) was the first approach to the HLA typing at molecular level. Although serology and RFLP methods define HLA specificities at low resolution level, RFLP has been considered to be better than serology. In this study, we performed HLA classe II (HLA-DR and DQ) typing comparing these two methods