Wasserfall Clive H, Atkinson Mark A
Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Health Science Center, 1600 SW Archer Road, Gainesville, FL 32610, USA.
Autoimmun Rev. 2006 Jul;5(6):424-8. doi: 10.1016/j.autrev.2005.12.002. Epub 2005 Dec 29.
Type 1 diabetes results from the autoimmune destruction of the insulin producing pancreatic beta-cells. For years, the notion that T-lymphocytes played a crucial role in the disorder's formation was considered such sound dogma, that interest in B-lymphocytes and autoantibodies as pathogenic variables was largely relegated to second-class status. However, much of our knowledge regarding the pathogenesis and natural history of this disease has been afforded by analysis of subjects having type 1 diabetes associated autoantibodies. While autoantibodies to more than two dozen autoantigens have been associated with this disease, a majority of interest has been directed at four autoantibodies; islet cell cytoplasmic (ICA), insulin (IAA), glutamic acid decarboxylase (GADA), and IA2/ICA512 autoantigen (IA2A). These autoantibodies, combined with other metabolic and genetic markers, are extremely effective for predicting eventual development of type 1 diabetes in otherwise healthy individuals. These autoantibodies have also aided in our understanding of disease heterogeneity and suggest that the autoimmune processes underlying type 1 diabetes initiate in the earliest stages of life (e.g., initial autoantibody formation at 9-18 months of age). Additional improvements are needed to more accurately define the time to disease onset, response to therapeutic intervention, the pathogenic features of the autoimmune response, and perhaps even the quantity of residual beta cell function.
1型糖尿病是由产生胰岛素的胰腺β细胞的自身免疫性破坏所致。多年来，T淋巴细胞在该疾病形成中起关键作用这一观点被视为确凿的教条，以至于作为致病变量的B淋巴细胞和自身抗体很大程度上被降至次要地位。然而，我们关于这种疾病发病机制和自然史的许多知识是通过对患有1型糖尿病相关自身抗体的受试者进行分析而获得的。虽然已发现二十多种自身抗原的自身抗体与这种疾病相关，但大部分研究兴趣集中在四种自身抗体上，即胰岛细胞胞浆抗体（ICA）、胰岛素自身抗体（IAA）、谷氨酸脱羧酶抗体（GADA）和IA2/ICA512自身抗原抗体（IA2A）。这些自身抗体与其他代谢和遗传标志物相结合，对于预测原本健康个体最终发生1型糖尿病极为有效。这些自身抗体也有助于我们理解疾病的异质性，并表明1型糖尿病潜在的自身免疫过程始于生命的最早阶段（例如，在9至18个月大时最初形成自身抗体）。还需要进一步改进，以更准确地确定疾病发病时间、对治疗干预的反应、自身免疫反应的致病特征，甚至可能确定残余β细胞功能的数量。
