?皮肤是我们抵抗感染的第一门户。当人们感染一种罕见的威胁生命的自身免疫病（称作寻常型天疱疮）时候，由于患者自身免疫系统攻击控制皮肤细胞聚集的蛋白而导致他们缺失这种保护，最终进展为严重的大水疱和绽开的溃疡使得其顶层与皮肤剥离，留下暴露的创伤口极容易导致严重的感染。
??那些能抑止免疫系统药物的发现是寻常型天疱疮和其他自身免疫疾病的患者的福音，可是这些药物自身对患者也是致死性的，通常引起严重的副作用。现在来自查佩尔希尔的北卡罗来纳大学的研究人员已经发现种更安全有效的方法治疗寻常型天疱疮患者。研究人员在小鼠模型上使用一种化合物，且已经明确这种化合物可以关闭激发皮肤损伤的信号而不遏制自身的免疫系统。
??该研究结果发表在今年8月份第22期《美国科学院院报》上。此项目获得了国立卫生机构的资助。来自北卡罗莱纳大学医学院皮肤与病理学系的副教授，北卡罗莱纳大学 Lineberger 癌症综合研究中心的成员，David S. Rubenstein博士认为：“即使我们不能阻止其免疫反应，但如果熟知由它所引起损伤背后的机制，我们就可以阻止这种损伤。针对在细胞中发生的特发事件可以使我们能更安全有效地治疗这类病人。”
??Rubenstein先前已经发现P38的酶是导致PV患者自身抗体引起损伤机制的组份。
??在PV的小鼠模型中，研究人员通过注射能抑止p38酶的药物来阻止起泡和发病的其他信号。试验显示抑止p38的药物不能阻止自身抗体结合到皮肤细胞。替代的是它能象发挥正常功能一样可以阻止损伤皮肤。这种药物终止一系列的细胞信号事件，这些信号导致皮肤细胞间黏附能力的散失。因此它能终止这种疾病而不影响其自身的免疫系统。
??Rubenstein认为：“现在有很多公司正在开发用于治疗类风湿关节炎以及银屑病的p38抑止剂，根据我们的研究结果建议那些药物可能在治疗pv病方面也有价值”。
??在该研究中用到的48只小鼠，其中24只小鼠被注射高剂量自身抗体来导致类似与人PV的大疱疹。另一组24只小鼠接受低剂量自身抗体导致不太严重的疱疹。每组一半的小鼠同时也接受p38抑止剂的治疗。
??在两组接受p38抑止剂处理的小鼠中，基本上没有小鼠呈现PV的临床前兆。例如在高剂量自身抗体处理组中，其中12只没有用p38抑止剂处理的有11只小鼠出现疱疹，而另12只用p38 抑止剂处理的仅有一只出现疱疹。
英文原文：
Scientists stop autoimmune disease without shutting off immune system
Skin is our first line of defense against infection. But people with a rare, life-threatening autoimmune disease called pemphigus vulgaris lack that protection because their immune system attacks the proteins that hold skin cells together. They develop severe blisters and raw sores as the top layer of their skin falls apart, leaving them extremely vulnerable to infection.
The development of drugs that completely suppress the immune system offered a lifeline to patients with pemphigus vulgaris (PV) and other autoimmune disorders, but the drugs themselves can be lethal and often cause serious side effects.
Now, researchers at the University of North Carolina at Chapel Hill have found a safer, more effective way to treat PV patients. In mice, the researchers used a known compound to turn off the signals that trigger skin damage without suppressing the immune system. Similar drugs being developed for human use could offer a potential treatment for PV, the researchers said.
The results appear in the Aug. 22 issue of Proceedings of the National Academy of Sciences. The research was funded the National Institutes of Health.
"Even if we can't block the immune response, if we can understand the mechanisms behind the damage it causes, we can block that damage," said Dr. David S. Rubenstein, associate professor in the department of dermatology in the UNC School of Medicine and a member of the UNC Lineberger Comprehensive Cancer Center. "Targeting these specific events in the cell could enable us to more effectively and safely treat patients."
Rubenstein has previously shown an enzyme called p38 is part of the mechanism by which pemphigus vulgaris autoantibodies cause damage. Autoantibodies are immune-system cells that attack the body's own tissues.
In a mouse model of pemphigus vulgaris, the researchers prevented blistering and other signs of the disease by injecting a drug that inhibits the p38 enzyme. Tests showed that the p38 inhibitor drug didn't prevent autoantibodies from binding to the skin cells. Instead, it prevented them from damaging the skin as they normally do. The drug stopped a series of cell-signaling events that lead to the loss of adhesion or "stickiness" between skin cells. Thus, it stops the disease without affecting the immune system.
"There are a number of companies developing inhibitors of the p38 enzyme for treating rheumatoid arthritis and psoriasis," Rubenstein said. "Our study suggests that those same drugs might be valuable in treating pemphigus vulgaris."
Of the 48 mice used in the study, 24 received a high dose of autoantibody which causes gross blistering akin to human PV. The other group of 24 received a lower dose that would cause less severe blistering. Half of each group also received treatment with a p38 inhibitor.
In the two groups that received p38 inhibitor treatment, almost no mice showed clinical signs of pemphigus vulgaris. For instance, in the group that received the high dose of pemphigus vulgaris antibody, 11 out of 12 mice showed blistering, but of the 12 mice that received also received the p38 inhibitor, only one showed blistering.
