第一型糖尿病(T1D)，也称为幼年型糖尿病，是一种多重致病因子的疾病，特征是自体免疫破坏胰脏β细胞，除了遗传上的易感性外，环境因素在催化疾病上也扮演一个重要的角色，病毒感染可能是最重要的关连，很多病毒如巨细胞病毒、腮腺炎病毒、风皮疹毒、肠病毒、小病毒的感染都和人类的T1D有关，不同病毒会诱导TID的作用也可以解释这疾病在一般大众发生的异质性及动态变化的本质。
最近新的免疫调节治疗对刚发生的糖尿病人可以保存残余的β细胞，因此有需要发展非侵入性的生物指标，能鉴定在变成临床上明显疾病之前自体反应的进展。在十一月份《实验生物及医学》(Experimental Biology and Medicine)期刊发表的文章，Kruger及其同事利用几个已知病毒诱导的TID大鼠模式找寻疾病发生早期的血清生物指标。Annnie Kruger、Rita Bortell及麻州大学医学院的同事共同进行这个研究，Kruger博士是一位刚毕业的MD/PhD，她的研究病毒诱导自体免疫糖尿病是她博士论文的一部份。
以蛋白体学研究病毒诱导糖尿病大鼠的血清，这研究团队用2D胶片及质谱仪分析，发现在糖尿病发生非常早之前，血清的亲血色球蛋白已增加，这结果也用西方墨点及ELISA证实，血清中持续增加的亲血色球蛋白可以预测未来发展成糖尿病。Bortell博士说明＂ 非常有趣地，人类亲血色球蛋白的突变和糖尿病的并发症如视网膜病变、肾病变、及心血管疾病的增加都相关。在我们大鼠的研究，亲血色球蛋白在病毒注射之后，非常早期远比发生糖尿病或并发症之前即出现，因此可以视为自体免疫糖尿病致病机制的一个生物指标。＂
对于研究人员的知识而言，这是第一个研究TID血清的生物指标，它对病毒感染有特异地反应。Bortell博士说明＂ 病毒感染过去被认为在小孩子和TID的发生有关连性，这些大鼠模式和人类疾病有很好的相关性，如能在小孩子发展成糖尿病之前的非常早期可以确定的找到他们，提供了医生一个治疗的机会，利用药物可以很有效地减缓或阻断疾病的进行。＂
《实验生物及医学》期刊主编Steven R. Goodman说 ＂Kruger等人已鉴定亲血色球蛋白是一个早期的血清生物指标，在已知的大鼠模式可以预测病毒诱导的TID，这个发现配合已知的遗传易感性指标，在鉴定那些容易发生TID的小孩可以证明是有用的。＂
推荐英文摘要：
Exp. Biol. Med. doi:10.1258/ebm.2010.010f10
Haptoglobin as an early serum biomarker of virus-induced type 1 diabetes in genetically susceptible rats
Type 1 diabetes (T1D), formerly known as juvenile diabetes, is a multifactorial disease of complex etiology characterized by the autoimmune destruction of pancreatic beta-cells. In addition to genetic susceptibility, it is generally accepted that environmental factors play important roles in triggering the disease, with virus infection having perhaps the strongest association. Multiple viral infections including cytomegalovirus, mumps, rubella, enteroviruses and parvovirus have all been associated with human T1D. Indeed, the effects of diverse viruses in triggering T1D may explain the heterogeneous nature of disease onset and kinetics in the general population.
The recent availability of novel immunomodulatory therapies that may preserve residual beta-cell mass in new onset diabetics has generated a demand for non-invasive testable biomarkers that can identify the development of the autoreactive process before it becomes clinically apparent. In the work published on page 1328 of this issue of Experimental Biology and Medicine, Kruger and co-workers have utilized several well-established rat models of virus-induced T1D to search for serum biomarkers that occur early in disease development. Annie Kruger, working together with Rita Bortell and other colleagues at the University of Massachusetts Medical School, carried out the work. Dr Kruger, a recent MD/PhD graduate, investigated the viral induction of autoimmune diabetes as part of her PhD thesis.
In a proteomics study of serum from rats treated with diabetogenic virus, the research team utilized two-dimensional gel analysis and mass spectrometry and found increased levels of serum haptoglobin very early in the time course of diabetes induction. This result was confirmed by Western blot and enzyme-linked immunosorbent assay analyses, and sustained elevations of serum haptoglobin were generally predictive of ensuing diabetes. ˉIntriguingly,ˇ Dr Bortell stated, ˉmutations in the human haptoglobin gene are associated with increased risk of diabetic complications such as retinopathy, nephropathy and cardiovascular disease. In our rat studies, however, haptoglobin was identified very early following virus infection, well prior to the development of diabetes or its complications, and thus may represent a biomarker for the pathogenesis of autoimmune diabetes as well.ˇ
To the researchers' knowledge, this is the first study that investigates T1D serum biomarkers found specifically in response to virus infection. Dr Bortell said ˉAs virus infections have historically been associated with the development of T1D in children, these rat models have particular relevance to the human disease. Reliably identifying children in the earliest phases of diabetes (pre-diabetes) would provide clinicians with a window of opportunity when pharmacotherapy could be most effective in slowing or halting the disease.ˇ
Steven R Goodman, Editor-in-Chief of Experimental Biology and Medicine, said ˉKruger et al. have identified haptoglobin as an early serum biomarker predictive of virus-induced T1D utilizing well-known rat models. This discovery, in conjunction with established markers of genetic susceptibility, should prove useful in identifying those children at risk for T1D.
