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A middle-aged woman—call her Anne—was taken aback when one day her right hand refused to hold a pen.A few weeks later her right foot began to drag reluctantly behind her left.After her symptoms worsened over months,she consulted a neurologist.Anne,it turned out,was suffering from multiple sclerosis,a potentially disabling type of autoimmune disease.The immune system normally jumps into action in response to bacteria and viruses,deploying antibodies,other molecules and various white blood cells to recognize and destroy trespassers.But in autoimmune disorders,components of the body’s immune system target one or more of the person’s own tissues.In Anne’s case,her defensive system had begun to turn against her nerves,eroding her ability to move.

Every story of autoimmune disease is sad,but collectively the impact of these illnesses is staggering.More than 40 autoimmune conditions have been identified,including such common examples as type 1 (insulin-dependent) diabetes,rheumatoid arthritis and celiac disease.Together they constitute the third leading cause of sickness and death after heart disease and cancer.And they afflict between 5 and 8 percent of the U.S.population,racking up an annual medical bill in the tens of billions of dollars.

Recent findings offer a way to brighten this gloomy picture.In the past 10 years a growing number of studies have revealed that the body makes certain antibodies directed against itself—otherwise known as autoantibodies—years,and sometimes a decade,before autoimmunity causes clinical disease,damaging tissues so much that people begin showing symptoms.This profound insight is changing the way that doctors and researches think about autoimmune conditions and how long they take to arise.It suggests that physicians might one day screen a healthy person’s blood for certain autoantibodies and foretell whether a specific disease is likely to develop years down the line.Armed with such predictions,patients could start fighting the ailment with drugs or other available interventions,thereby preventing or delaying symptoms.

Those interventions may not be easy to find; most likely,preventive therapy would have to be tailored specifically for each condition.In certain disorders,such as myasthenia gravis,autoantibodies participate in the disease process,and so blocking the activity of the particular autoantibodies at fault could be therapeutic.Autoantibodies that presage certain other conditions,though,probably are more siren than fire,announcing brewing disease actually caused by other components of the immune system,such as cells known as T lymphocytes and macrophages.In those cases,preventive treatments would have to target the offending cells.

The revolution in predictive medicine and preventive care will take time and effort to effect.Many autoantibodies have been uncovered,but only a few large scale trials have been conducted to evaluate how accurately they can predict disease.If inexpensive,quick tests for predictive autoantibodies can be developed,though,they could become as standard part of routine checkups as cholesterol monitoring.

People familiar with advances in genetics might wonder why researchers would want to develop tests for predictive autoantibodies when doctors might soon be able to scan a person’s genes for those that put the individual at risk of various disorders.The answer is that most chronic diseases arise from a complex interplay between environmental influences and multiple genes (each of which makes but a small contribution to a disease).So detection of susceptibility genes would not necessarily reveal with any certainty whether or when an individual will come down with a particular autoimmune condition.In contrast,detection of specific autoantibodies would signal that a disease-causing process was already under way.Eventually,genetic screening for those with an inherited predisposition to a disease may help reveal those who need early antoantibody screening.

Studies of patients with type 1 diabetes provided the first clues that autoantibodies could be valuable for predicting later illness.In this condition,which typically arises in children or teenagers,the immune system ambushes the beta cells in the pancreas.These cells are the manufacturers of insulin,a hormone that enables cells to take up vital glucose from the blood for energy.When the body lacks insulin,cells starve and blood glucose level soar,potentially leading to blindness,kidney failure,and a host of other complications.

Forty years ago type 1 diabetes was not yet recognized as an autoimmune disease,and no one knew what caused the beta cells to die.But in the 1970s Willy Gepts of Vrije University of Brussels in Belgium examined the pancreases of children who had died of the disease and found that the islets of Langerhans,where the beta cells reside,had been infiltrated by lymphocytes—a sign of probable autoimmune activity.Soon thereafter Franco Bottazzo of Middlesex Hospital Medical School in London established that blood from patients with type 1 diabetes reacted to islets but that blood of nondiabetics did not,which suggested that autoantibodies targeted to the diabetics’ own beta cells were circulating in the patients’ blood.This finding set off a hunt for the autoantigens—the specific molecular targets of the autoantibodies—in the beta cells,because researchers hoped that discovery of the autoantigens would clarify how diabetes arises.

Intensive research over the past 20 years has uncovered three major pancreatic autoantigens produced in people with newly diagnosed type 1 diabetes: insulin itself,an enzyme called glutamic acid decarboxylase (GAD) and a protein known as islet antigen-2 (IA-2),which was discovered by my group at the National Institutes of Health and is a component of the tiny sacs that ferry insulin around in beta cells.Experts still do not know whether the autoantibodies that bind these proteins play a part in killing beta cells.But they do know,based on highly sensitive detection tests,that one or more are present at diagnosis in some 70 to 90 percent of patients with type 1 diabetes.Today research laboratories use these tests to diagnose type 1 diabetes and distinguish it from type 2 diabetes,which usually arises in overweight adults and does not stem from autoimmunity.(Surprisingly,such tests have uncovered autoantibodies in about 5 percent of patients otherwise diagnosed with type 2 diabetes,which suggests that those individuals have been misclassified or have a combination of type 1 and type 2 diabetes.)

The discovery that autoantibodies frequently herald the onset of type 1 diabetes prompted scientists to examine whether the same might be true in other autoimmune diseases.One that has been the focus of especially intense research is rheumatoid arthritis,a debilitating condition that is highly prevalent,afflicting about 1 percent of the world’s population.In those affected,the immune system attacks and destroys the lining of the joints,causing swelling,chronic pain and eventual loss of movement.（1,113 words）

neurologist　n.神经科医师

multiple sclerosis　n.多发性硬化症

autoimmune　adj.自身免疫的

trespasser　n.侵犯者

staggering　adj.难以置信的

condition　n.疾病

insulin-dependent　adj.胰岛素依赖型

rheumatoid arthritis　n.类风湿性关节炎

celiac disease　n.乳糜泻（麸质不适应症）

rack (up) v.积累；取得

autoantibody　n.自身抗体

ailment　n.疾病（尤指慢性病）

thereby　adv.因而

myasthenia gravis　n.重症肌无力

presage　v.预兆；预示

brew　v.酝酿；策划

lymphocyte　n.（出现在血液、淋巴液中的）淋巴细胞

macrophage　n.巨噬细胞

interplay　n.相互作用

susceptibility gene　n.易感基因（容易受到影响的基因）

predisposition　n.易患病的体质

insulin　n.胰岛素

hormone　n.（刺激生长的）荷尔蒙；激素

glucose　n.葡萄糖

kidney failure　n.肾功能衰竭

complication　n.并发症

islets of Langerhans　n.朗格罕氏症（胰岛）

infiltrate　v.使渗透

autoantigen　n.自身抗原

enzyme　n.（生化）酶

glutamic acid decarboxylase　n.谷氨酸脱羧酶（GAD）

protein　n.蛋白质

islet antigen-2　n.胰岛抗原2（IA-2）

debilitating　adj.使（人或人的身体）非常虚弱的

lining　n.组织；膜

1.type 1 diabetes：第一型糖尿病。又叫青年发病型糖尿病，常在35岁以前发病。第一型糖尿病是终身依赖胰岛素治疗的。原因在于第一型糖尿病病友体内胰腺产生胰岛素的细胞已经彻底破坏，从而完全失去了产生胰岛素的功能。

2.T lymphocyte：胸腺依赖淋巴细胞（thymus dependent lymphocyte）。来源于骨髓的多能干细胞（胚胎期则来源于卵黄囊和肝）。成熟的T细胞经血液分布至外周免疫器官的胸腺依赖区定居，并可经淋巴管、外周血和组织液等进行再循环，发挥细胞免疫及免疫调节等功能。

3.macrophage：巨噬细胞。由游出血管的单核细胞衍变而成的细胞。体积较大，形状不规则，常伸出短而钝的突起，做变形运动，能吞噬死亡的细胞和侵入体内的细菌，形成吞噬体，在免疫反应中起重要作用。

4.beta cell：β细胞。是含有碱性颗粒的腺细胞，存在于脑下垂体前叶和胰脏的胰岛内。脑下垂体前叶的β细胞分泌生殖腺刺激激素。胰岛中的β细胞分泌胰岛素。

1.【原文】In Anne’s case,her defensive system had begun to turn against her nerves,eroding her ability to move.

【译文】安妮的自身防御系统已经开始攻击她的神经，使她逐渐丧失活动能力。

【解析】翻译本句时，如果照原文将“In Anne’s case”直译为“在安妮的病例中”，将使译文显得累赘。因此，译文中省略了这个短语。

2.【原文】More than 40 autoimmune conditions have been identified,including such common examples as type 1 (insulin-dependent) diabetes,rheumatoid arthritis and celiac disease.

【译文】目前已经识别的自身免疫疾病有40余种，其中包括很常见的第一型（胰岛素依赖型）糖尿病、类风湿性关节炎以及乳糜泻。

【解析】本句为被动句。译文中将原文的被动句式处理为主动句式，更符合汉语习惯。

3.【原文】Together they constitute the third leading cause of sickness and death after heart disease and cancer.

【译文】它们紧随心脏病和癌症之后，是造成人类生病甚至死亡的第三大原因。

【解析】本句在翻译时，对原文语序进行了调整并进行了分句处理，“after heart disease and cancer”被提到了句首部分，译为“它们紧随心脏病和癌症之后”，这样读起来更加通顺，行文也更利索。

4.【原文】In the past 10 years a growing number of studies have revealed that the body makes certain antibodies directed against itself—otherwise known as autoantibodies—years,and sometimes a decade,before autoimmunity causes clinical disease,damaging tissues so much that people begin showing symptoms.

【译文】过去10年中，越来越多的研究发现人体会产生某些针对自身的抗体，称为自身抗体。这种抗体在自身免疫系统引发临床疾病，破坏人体组织，病人在发病前几年甚至十年就开始出现这些症状。

【解析】原文是一个结构较为复杂的长句。在翻译时，如果依照原文将译文处理为同样结构的长句，显然是不符合汉语表达习惯的。因此，在译文中，原文被分解为相对应的两句。

5.【原文】The answer is that most chronic diseases arise from a complex interplay between environmental influences and multiple genes (each of which makes but a small contribution to a disease).

【译文】原因是大多数慢性疾病是由环境以及多基因（尽管单个基因造成疾病的可能性小，每种基因都是形成疾病的原因）的相互作用产生的非常复杂的影响造成的。

【解析】原句定语性形容词“complex”，在译文中被处理为独立的分句“这种影响非常复杂”，置于句后。这样处理虽然加长了译文长度，却更加通顺流畅。

6.【原文】In this condition,which typically arises in children or teenagers,the immune system ambushes the beta cells in the pancreas.

【译文】患有这类疾病的人群主要为儿童或青少年，他们的免疫系统攻击胰腺内的β细胞。

【解析】原文非限制性定语从句“which typically arises in children and teenagers”，在译文中作为独立分句译出置于句首。

7.【原文】Today research laboratories use these tests to diagnose type 1 diabetes and distinguish it from type 2 diabetes,which usually arises in overweight adults and does not stem from autoimmunity.

【译文】今天，研究工作实验室利用这些测试来诊断第一型糖尿病，并用来区分第二型糖尿病。第二型糖尿病不是由自身免疫造成的，其患者常为体型超标的成年人。

【解析】本句涉及非限制性定语从句的翻译以及分句的技巧。原文“which usually arises in overweight adults and does not stem from autoimmunity”在译文中独立出现，其行文顺序亦发生改变，“第二型糖尿病不是由自身免疫造成的，其患者常为体型超标的成年人”。

8.【原文】One that has been the focus of especially intense research is rheumatoid arthritis,a debilitating condition that is highly prevalent,afflicting about 1 percent of the world’s population.

【译文】在目前进行的大量研究中，重点之一就是对于类风湿性关节炎的研究。类风湿性关节炎很常见，它会给病人带来极大痛苦。世界上约有1%的人患有这种疾病。

【解析】原文虽短，但句式结构较为复杂。主句为“One that has been the focus of especially intense research is rheumatoid arthritis”，同位语从句为“a debilitating condition that is highly prevalent,afflicting about 1 percent of the world’s population”，其中同位语从句中又包含一个定语从句“that is highly prevalent”以及一个伴随状语从句“afflicting about 1 percent of the world’s population”。翻译时，如果照原文直译出，其译文结构不但会冗长不堪，同时会影响读者的理解。所以，译文对原文进行了分句处理，打乱了原文顺序，重新按照汉语习惯进行组合。

一位中年妇女，我们叫她安妮吧，有一天突然发现自己的右手竟然拿不动笔了，这真让她吓了一跳。几周后，她的右脚也慢慢地跟不上左脚的速度了。随后几个月内，症状逐渐恶化。她只得去咨询神经科医师。原来，她得了一种叫做多发性硬化症的病。这是一种自身免疫疾病，有可能会造成身体残疾。人体免疫系统通常会对入侵的细菌和病毒采取突然行动，部署抗体、其他免疫分子和各种白血球细胞来辨识并消灭入侵者。但是自身免疫紊乱时，人体免疫系统就会攻击一个或多个人体自身组织。安妮的自身防御系统已经开始攻击她的神经，使她逐渐丧失活动能力。

每一例自身免疫疾病都让人痛心，但总体而言，这类疾病的后果令人吃惊。目前已经识别的自身免疫疾病有40余种，其中包括很常见的第一型（胰岛素依赖型）糖尿病、类风湿性关节炎以及乳糜泻。它们紧随心脏病和癌症之后，是造成人类生病甚至死亡的第三大原因。5%至8%的美国人被这些疾病所折磨，每年的医疗费用高达数百亿美元。

最新的一些发现可以改变这种让人沮丧的局面。在过去10年中，越来越多的研究发现人体会产生某些针对自身的抗体，称为自身抗体。这种抗体在自身免疫系统引发临床疾病，破坏人体组织，病人在发病前几年甚至十年就开始出现这些症状。这些发现意义重大，改变着医生和研究人员对于自身免疫疾病及其出现症状的时间的看法。它意味着也许有一天，医生们只要测验健康人血液中是否存在某种自身抗体，就可以预测其在将来几年中有无可能患上某种疾病。有了这样的预测，病人就可以开始服用药物或者采取其他可行的干预措施来对抗疾病，从而预防或者延迟症状的出现。

找到干预措施并不是件容易的事。最可能出现的情况是不同类型的病人必须采取不同的预防性治疗。在某些免疫紊乱疾病中，如重症肌无力，自身抗体参与到了疾病过程之中。因此，阻止某些发生故障的自身抗体的活动可以起到治疗作用。然而，预示其他疾病的自身抗体可能只是警报而非真的火灾，也就是说它们宣告具有免疫系统的其他成员，如T淋巴细胞和巨噬细胞，正策划疾病来捣乱。这时候，预防治疗需要针对的应该是致病细胞。

预防药物以及预防治疗领域的革命要想发挥作用还需要人们花费很多的时间和精力。目前已被发现的自身抗体有很多种，但是评估其预示疾病准确性的大型试验仅仅进行过几次。如果能够找到一种耗费较低的方式快速检验预示性自身抗体，这种检查极有可能成为常规体检的一部分，就像监测人体的胆固醇含量一样。

熟悉遗传学发展的人可能会感到疑惑，为什么在不久的将来，既然医生可以通过扫描某人的基因来判断此人是否有患病的危险，为什么研究人员还要开发预示性自身抗体试验呢？原因是大多数慢性疾病是由环境以及多种基因（尽管单个基因造成疾病的可能性小，每种基因都是形成疾病的原因）的相互作用产生的非常复杂的影响造成的。所以检测到易感基因，并不意味着可以准确预测人是否以及何时将患上某种自身免疫疾病。相反，检测某些自身抗体则能表明某种引起疾病的过程已经被启动。最终，对于遗传性易患病体质的基因筛查将有助于揭示哪些人需要做早期自身抗体检测。

基于第一型糖尿病病人的研究首次提供了一些证据，说明自身抗体有助于预测疾病。患有这类疾病的人群主要为儿童或青少年，他们的免疫系统攻击胰腺内的β细胞。这些细胞分泌胰岛素，促使细胞从血液中吸取必须的葡萄糖以获取能量。人体一旦缺少胰岛素，这些细胞就会衰竭，血液中的葡萄糖含量随之大幅增高，进而可能引起失明、肾功能衰竭以及大量并发症。40年前，人们尚未把第一型糖尿病看作自身免疫疾病，无人知道β细胞衰竭的原因。直到20世纪70年代，比利时布鲁塞尔自由大学的威利·杰普兹在研究死于该疾病的儿童胰腺后发现，β细胞所聚居的胰岛已经被淋巴细胞渗透。这一点说明自身免疫系统已经在发挥作用了。此后不久，伦敦米德尔塞克斯医学院的弗朗克·博塔佐证实第一型糖尿病病人的血液对胰岛有反应，而非糖尿病人的血液则没有。这说明病人身体流淌的血液中存在针对其自身β细胞的自身抗体。这一发现使研究人员开始在β细胞中寻找自身抗原（自身抗体的特定分子目标），因为研究人员希望通过自身抗原的发现来帮助搞清糖尿病的起因。

过去20年的大量研究促使人们发现了三种主要的胰腺自身抗原，这些抗原是在那些最近被诊断为患有第一型糖尿病的病人身上发现的，它们分别是：胰岛素本身，谷氨酸脱羧酶（GAD），以及一种叫做胰岛抗原2（IA-2）的蛋白质。这种叫做胰岛抗原2的蛋白质是我所在的国家卫生研究所的研究小组发现的。它是在β细胞内部运送胰岛素的微型液囊的组成部分。截至目前，专家们仍然无法确定凝固这些蛋白质的自身抗体是否在杀死β细胞的过程中发挥了作用。但通过精确度很高的检测测试可以确定的是，70%到90%患有第一型糖尿病的病人体内都存在一个或多个自身抗体。今天，很多研究实验室利用这些测试来诊断第一型糖尿病，并用来区分第二型糖尿病。第二型糖尿病不是由自身免疫造成的，其患者常为体重超标的成年人。（令人惊讶的是，在被诊断出患有第二型糖尿病的患者中，还有大约百分之五的人通过这些实验检测出带有自身抗体，这表明这些人可能是被错误诊断，也有可能他们同时患有第一型和第二型糖尿病。）

自身抗体通常是第一型糖尿病的前兆。这一发现促使科学家研究它是否也是其他自身免疫疾病的前兆。在目前进行的大量研究中，重点之一就是对于类风湿性关节炎的研究。类风湿性关节炎是一种很常见的疾病，它会给病人带来极大痛苦。世界上约有1%的人患有这种疾病。在患者体内，免疫系统攻击并破坏关节组织，引发肿胀、长期疼痛，并最终使患者失去活动能力。