一项最新的蛋白质组研究在免疫细胞中发现了一种蛋白质，它有可能成为一种可靠的精神分裂症患病风险标记物。
精神分裂症是一种严重而又很复杂的精神疾病，大约有1%的人受到这种疾病困扰。目前的诊断依赖于临床面诊的主观判断以及对不明确症状的评估，这往往会造成诊断和治疗的延误。因此，生物标记物有可能成为指示精神分裂症患病风险和发病的有效诊断手段。
Sabine Bahn及其同事希望在血液中找到可以用于诊断精神分裂症的一种“蛋白质指纹印迹”。他们用质谱比较了精神分裂症患者和正常人的蛋白质谱，鉴定出两个发生显著变化的峰值。经过鉴定，这两种蛋白质都是α-防御素，这是一种先天免疫应答反应中用于杀灭微生物和病毒的蛋白质。
Sabine Bahn及其同事通过检测α-防御素在21对精神分裂症患者对比组（其中一个已经确诊患病而另一个没有）的血液中的水平来验证他们的发现。在这些对比组中，与对照者相比，所有确诊患者的α-防御素水平都有显著升高。在一些刚刚诊断出的患者中也发现了这种变化，这说明高水平的α-防御素不是由药物或疾病的发展进程引起的。
由于患者对比组中的两个人都有α-防御素升高的情况，所以这种蛋白质不能指示发病情况，但是研究者们认为，它们可以作为一种评价精神分裂症患病风险的有效而简易的标记物。他们认为，开发一种灵敏、特异的精神分裂症血液检测方法还需要更多的标记物。相关论文发表在《分子与细胞蛋白质组学》（Molecular & Cellular Proteomics）上。（生物谷Bioon.com）
生物谷推荐原始出处：
Molecular & Cellular Proteomics，7:1204-1213, 2008，Rachel M. Craddock，Sabine Bahn
Increased -Defensins as a Blood Marker for Schizophrenia Susceptibility*
Rachel M. Craddock, Jeffrey T. Huang, Edmund Jackson, Nathan Harris¶, E. Fuller Torrey||, Marlis Herberth and Sabine Bahn,**
From the Institute of Biotechnology, University of Cambridge, Cambridge CB2 1QT, United Kingdom, Department of Engineering, University of Cambridge, Cambridge CB2 1PZ, United Kingdom, ¶ Ciphergen Biosystems, Freemont, California 94555, and || Stanley Laboratory of Brain Research, Department of Psychiatry, Uniformed Services University for the Health Sciences, Bethesda, Maryland 20814
Schizophrenia is a severe psychotic illness affecting 1% of the general population. There are no consistent pathological features, and the disorder is defined by a complex symptomatology, which overlaps with other psychiatric illnesses. Diagnosis is based on a clinical interview, relying on the patient meeting criteria according to diagnosis manuals, including Diagnostic and Statistical Manual of Mental Disorders, 4th Ed. and International Statistical Classification of Diseases, 10th Revision. Because of the ambiguous symptoms, the diagnostic process can take many months and often years. Rapid and effective treatment has been shown to impact positively on disease progression and outcome, and it is therefore important to identify disease-associated biomarkers allowing early diagnosis. Reliable biomarkers can be used for the development of diagnostic tests and may also help us understand the underlying pathology of this disorder. In the present study, proteins from anti-CD3 stimulated and unstimulated peripheral blood T cell lysates from 15 minimally medicated and unmedicated patients and 15 age-, sex-, race-, and smoking-matched controls were profiled on cation exchange (CM10) chips using SELDI-TOF. Partial least squares discriminate analysis was used to separate patient and control groups according to the expression of 108 detected peaks, and two peaks of 3,374 and 3,450 Da, corresponding to -defensins based on masses and cationic properties, were found to contribute significantly to the separation of patient and control groups. Reduction of T cell lysates with DTT resulted in a 6-Da shift in the mass of these peaks consistent with the presence of three cysteine bonds in the structure, confirming them as -defensins. Quantification of -defensins in T cell lysates from six patients and 18 healthy controls was carried out by ELISA, which also showed that -defensin levels were significantly increased in patient lysates when compared with matched controls (p = 0.0197). Plasma from 21 monozygotic twins discordant for schizophrenia and eight healthy unaffected twin pairs was also analyzed for the expression of -defensins by ELISA. Notably both affected and unaffected twins were found to have significantly elevated -defensin levels compared with healthy control twin pairs (p = 0.0014 and p = 0.0115, respectively). Increased expression of -defensins in unaffected as well as affected discordant monozygotic twins is of particular interest as monozygotic twins share genes and usually environmental upbringing. The unaffected twin therefore represents the biological and environmental risk of developing schizophrenia in the absence of overt symptomatology and therapeutic medication. These findings suggest that -defensins could be an important early indicator of the risk of schizophrenia.
