Bour-Jordan Hélène, Bluestone Jeffrey A
Diabetes Center, Department of Medicine, UCSF, San Francisco, California 94143-0540, USA.
J Clin Invest. 2007 Dec;117(12):3642-5. doi: 10.1172/JCI34236.
Autoimmune diabetes is believed to be mediated primarily by T cells. However, B cells have been implicated in the pathogenesis of the disease in NOD mice. Although preclinical studies have been limited by the absence of anti-CD20 reagents that can induce B cell depletion in mice, a clinical trial using the B cell-depleting anti-CD20 monoclonal antibody rituximab (Rituxan) is underway in type 1 diabetes patients. In this issue of the JCI, Hu et al. describe the generation of transgenic NOD mice that express human CD20 on B cells (see the related article beginning on page 3857). They show that anti-CD20 therapy induces B cell depletion in these mice and offers some level of protection against diabetes. Although many questions remain unanswered, this mouse model represents the first opportunity to evaluate the potential value of rituximab as a novel therapy for autoimmune diabetes.
自身免疫性糖尿病被认为主要由T细胞介导。然而，在非肥胖糖尿病（NOD）小鼠中，B细胞也与该疾病的发病机制有关。尽管临床前研究因缺乏能在小鼠中诱导B细胞耗竭的抗CD20试剂而受到限制，但一项使用耗竭B细胞的抗CD20单克隆抗体利妥昔单抗（美罗华）的1型糖尿病患者临床试验正在进行。在本期《临床研究杂志》（JCI）中，胡等人描述了在B细胞上表达人CD20的转基因NOD小鼠的产生（见第3857页开始的相关文章）。他们表明，抗CD20疗法可诱导这些小鼠的B细胞耗竭，并提供一定程度的糖尿病保护。尽管许多问题仍未得到解答，但该小鼠模型代表了评估利妥昔单抗作为自身免疫性糖尿病新疗法潜在价值的首个机会。
