一般来说，当病毒或细菌侵入人体后，免疫系统会加速运转，与入侵者战斗以将它们驱逐出去。当入侵者被消灭后，身体会启动“刹车”装置，停止免疫反应。然而美国、英国及加拿大科学家近日研究发现，一种名为TNFAIP3的特殊基因突变可能会导致免疫系统在“危险”解除后仍旧保持很长时间的全速运转，从而对机体造成损害。相关论文8月1日在线发表于《自然—遗传学》（Nature Genetics）上。
论文高级作者、美国俄克拉荷马医学研究基金会的Patrick Gaffney说：“TNFAIP3可看作是免疫系统的一个紧急刹车机制。当它的功能发挥出现故障时，免疫系统就会高速运转不止。”
狼疮（lupus）就是一个典型的例子。它是一种慢性自体免疫性疾病，患者的免疫系统会攻击健康的组织和器官。症状有皮疹、关节痛、中风以及器官衰竭等。Gaffney表示，在健康个体身上，正常版本的TNFAIP3会产生一种名为A20的蛋白，它能调控关闭免疫反应；而狼疮患者携带的是该基因的突变体，导致免疫系统无法关闭自身。
Gaffney说：“我们推测，该突变体要么是产生的A20蛋白量不够，要么是它产生了另一种低效的蛋白。”狼疮是一种受多基因控制的疾病，意味着单一基因并不会导致该病。不过TNFAIP3突变有可能与其它突变基因协同作用，在一些患者身上导致狼疮。
论文另一作者Kathy Moser说：“我们发现的每个与狼疮有关的基因都与其它的一样重要，你永远不知道哪个基因会给你提供最好的机会，去开发新的治疗手段或更好的诊断方法。”（生物谷Bioon.com）
生物谷推荐原始出处：
Nature Genetics，doi:10.1038/ng.200，Robert R Graham，Patrick M Gaffney
Genetic variants near TNFAIP3 on 6q23 are associated with systemic lupus erythematosus
Robert R Graham1,11,12, Chris Cotsapas1,2,12, Leela Davies1, Rachel Hackett1, Christopher J Lessard3,4, Joanlise M Leon5, Noel P Burtt1, Candace Guiducci1, Melissa Parkin1, Casey Gates1, Robert M Plenge1, Timothy W Behrens6, Joan E Wither7, John D Rioux8, Paul R Fortin9, Deborah Cunninghame Graham10, Andrew K Wong10, Timothy J Vyse10, Mark J Daly1,2, David Altshuler1, Kathy L Moser4 & Patrick M Gaffney4
Systemic lupus erythematosus (SLE) is an autoimmune disease influenced by genetic and environmental factors. We carried out a genome-wide association scan and replication study and found an association between SLE and a variant in TNFAIP3 (rs5029939, meta-analysis P = 2.89 10-12, OR = 2.29). We also found evidence of two independent signals near TNFAIP3 associated with SLE, including one previously associated with rheumatoid arthritis (RA). These results establish that variants near TNFAIP3 contribute to differential risk of SLE and RA.
Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA.
Center for Human Genetic Research, Mass General Hospital, 185 Cambridge Street, and the Department of Medicine, Harvard Medical School, Boston, Massachusetts 02114, USA.
Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, USA.
Arthritis and Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104, USA.
Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, USA.
Arthritis Centre of Excellence; Division of Genetics and Development, Toronto Western Hospital Research Institute, University Health Network; Departments of Medicine and Immunology, University of Toronto, Toronto, Ontario, Canada.
Université de Montréal and the Montreal Heart Institute Research Center, Montreal, Quebec, Canada.
University of Toronto Lupus Clinic, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, University Health Network; Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
Molecular Genetics and Rheumatology Section, Imperial College Faculty of Medicine, Hammersmith Hospital, London, UK.
Present address: Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, USA.
These authors contributed equally to this work.
