RESUMO
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.
Assuntos
Anticorpos Monoclonais/administração & dosagem , Doenças Autoimunes/tratamento farmacológico , Complexo CD3/química , Diabetes Mellitus Tipo 1/tratamento farmacológico , Células Secretoras de Insulina/efeitos dos fármacos , Insulina/metabolismo , Interleucina-1beta/antagonistas & inibidores , Animais , Anticorpos Monoclonais/química , Anticorpos Monoclonais/uso terapêutico , Doenças Autoimunes/imunologia , Doenças Autoimunes/metabolismo , Pesquisa Biomédica/métodos , Complexo CD3/metabolismo , Diabetes Mellitus Tipo 1/imunologia , Diabetes Mellitus Tipo 1/metabolismo , Esquema de Medicação , Quimioterapia Combinada , Feminino , Fragmentos Fab das Imunoglobulinas/administração & dosagem , Fragmentos Fab das Imunoglobulinas/química , Fragmentos Fab das Imunoglobulinas/uso terapêutico , Imunoterapia/métodos , Secreção de Insulina , Células Secretoras de Insulina/imunologia , Células Secretoras de Insulina/metabolismo , Proteína Acessória do Receptor de Interleucina-1/antagonistas & inibidores , Proteína Acessória do Receptor de Interleucina-1/metabolismo , Interleucina-1beta/metabolismo , Camundongos Endogâmicos NOD , Estudos Multicêntricos como Assunto , Projetos Piloto , Receptores Tipo I de Interleucina-1/antagonistas & inibidores , Receptores Tipo I de Interleucina-1/metabolismo , Proteínas Recombinantes de Fusão/uso terapêutico , Reprodutibilidade dos Testes , Projetos de Pesquisa , Organismos Livres de Patógenos Específicos , Estados UnidosRESUMO
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