一般來說,，當(dāng)病毒或細(xì)菌侵入人體后,，免疫系統(tǒng)會加速運(yùn)轉(zhuǎn),，與入侵者戰(zhàn)斗以將它們驅(qū)逐出去,。當(dāng)入侵者被消滅后,，身體會啟動“剎車”裝置，停止免疫反應(yīng),。然而美國,、英國及加拿大科學(xué)家近日研究發(fā)現(xiàn)，一種名為TNFAIP3的特殊基因突變可能會導(dǎo)致免疫系統(tǒng)在“危險(xiǎn)”解除后仍舊保持很長時(shí)間的全速運(yùn)轉(zhuǎn),，從而對機(jī)體造成損害,。相關(guān)論文8月1日在線發(fā)表于《自然—遺傳學(xué)》（Nature Genetics）上。
論文高級作者、美國俄克拉荷馬醫(yī)學(xué)研究基金會的Patrick Gaffney說：“TNFAIP3可看作是免疫系統(tǒng)的一個(gè)緊急剎車機(jī)制,。當(dāng)它的功能發(fā)揮出現(xiàn)故障時(shí),，免疫系統(tǒng)就會高速運(yùn)轉(zhuǎn)不止。”
狼瘡（lupus）就是一個(gè)典型的例子,。它是一種慢性自體免疫性疾病,，患者的免疫系統(tǒng)會攻擊健康的組織和器官。癥狀有皮疹,、關(guān)節(jié)痛,、中風(fēng)以及器官衰竭等。Gaffney表示,，在健康個(gè)體身上,，正常版本的TNFAIP3會產(chǎn)生一種名為A20的蛋白，它能調(diào)控關(guān)閉免疫反應(yīng),；而狼瘡患者攜帶的是該基因的突變體,，導(dǎo)致免疫系統(tǒng)無法關(guān)閉自身。
Gaffney說：“我們推測,，該突變體要么是產(chǎn)生的A20蛋白量不夠,，要么是它產(chǎn)生了另一種低效的蛋白。”狼瘡是一種受多基因控制的疾病,，意味著單一基因并不會導(dǎo)致該病,。不過TNFAIP3突變有可能與其它突變基因協(xié)同作用，在一些患者身上導(dǎo)致狼瘡,。
論文另一作者Kathy Moser說：“我們發(fā)現(xiàn)的每個(gè)與狼瘡有關(guān)的基因都與其它的一樣重要,，你永遠(yuǎn)不知道哪個(gè)基因會給你提供最好的機(jī)會，去開發(fā)新的治療手段或更好的診斷方法,。”（生物谷Bioon.com）
生物谷推薦原始出處：
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.
