Harrison Leonard C, Honeyman Margo C, Morahan Grant, Wentworth John M, Elkassaby Shirley, Colman Peter G, Fourlanos Spiros
The Walter & Eliza Hall Institute of Medical Research, Parkville 3050, Victoria, Australia.
J Autoimmun. 2008 Nov;31(3):306-10. doi: 10.1016/j.jaut.2008.04.026. Epub 2008 Jun 16.
Type 1 diabetes (T1D) satisfies many of the criteria for an autoimmune disease. The impact of the environment to promote the development of T1D and the ability to identify individuals at risk for T1D years before clinical presentation afford lessons for other autoimmune diseases, in regard to gene-environment interactions and the potential for rational approaches to pre-clinical diagnosis and prevention. Public health measures aimed at the modern pro-inflammatory environment are required to stem the rising tide not only of T1D but other autoimmune and chronic inflammatory disorders. In the non-obese diabetic (NOD) model of spontaneous autoimmune diabetes, compelling evidence indicates that adaptive autoimmunity to the pancreatic beta cell is initially targeted against proinsulin. Proof-of-principle studies in the NOD mouse, which established that insulin and proinsulin peptides could be applied as tools to induce immune tolerance and protect against diabetes development, await successful translation to at-risk humans. Initial trials of insulin-specific immunotherapy in humans show promise and reveal ways of optimising this approach that are also applicable to other autoimmune diseases.
1型糖尿病(T1D)符合自身免疫性疾病的许多标准。环境对T1D发病的促进作用,以及在临床表现出现前数年识别T1D高危个体的能力,为其他自身免疫性疾病在基因-环境相互作用以及临床前诊断和预防的合理方法潜力方面提供了经验教训。需要针对现代促炎环境采取公共卫生措施,以遏制不仅是T1D,还有其他自身免疫性和慢性炎症性疾病不断上升的趋势。在自发性自身免疫性糖尿病的非肥胖糖尿病(NOD)模型中,有力证据表明对胰腺β细胞的适应性自身免疫最初靶向胰岛素原。在NOD小鼠中进行的原理验证研究确定胰岛素和胰岛素原肽可作为诱导免疫耐受和预防糖尿病发生的工具,有待成功转化应用于高危人群。人类胰岛素特异性免疫疗法的初步试验显示出前景,并揭示了优化该方法的途径,这些途径也适用于其他自身免疫性疾病。