一項(xiàng)最新的蛋白質(zhì)組研究在免疫細(xì)胞中發(fā)現(xiàn)了一種蛋白質(zhì),，它有可能成為一種可靠的精神分裂癥患病風(fēng)險(xiǎn)標(biāo)記物。
精神分裂癥是一種嚴(yán)重而又很復(fù)雜的精神疾病,，大約有1%的人受到這種疾病困擾,。目前的診斷依賴于臨床面診的主觀判斷以及對不明確癥狀的評估，這往往會造成診斷和治療的延誤,。因此,，生物標(biāo)記物有可能成為指示精神分裂癥患病風(fēng)險(xiǎn)和發(fā)病的有效診斷手段。
Sabine Bahn及其同事希望在血液中找到可以用于診斷精神分裂癥的一種“蛋白質(zhì)指紋印跡”,。他們用質(zhì)譜比較了精神分裂癥患者和正常人的蛋白質(zhì)譜,，鑒定出兩個(gè)發(fā)生顯著變化的峰值。經(jīng)過鑒定,，這兩種蛋白質(zhì)都是α-防御素,，這是一種先天免疫應(yīng)答反應(yīng)中用于殺滅微生物和病毒的蛋白質(zhì)。
Sabine Bahn及其同事通過檢測α-防御素在21對精神分裂癥患者對比組（其中一個(gè)已經(jīng)確診患病而另一個(gè)沒有）的血液中的水平來驗(yàn)證他們的發(fā)現(xiàn),。在這些對比組中,，與對照者相比，所有確診患者的α-防御素水平都有顯著升高,。在一些剛剛診斷出的患者中也發(fā)現(xiàn)了這種變化，這說明高水平的α-防御素不是由藥物或疾病的發(fā)展進(jìn)程引起的,。
由于患者對比組中的兩個(gè)人都有α-防御素升高的情況,，所以這種蛋白質(zhì)不能指示發(fā)病情況，但是研究者們認(rèn)為,，它們可以作為一種評價(jià)精神分裂癥患病風(fēng)險(xiǎn)的有效而簡易的標(biāo)記物,。他們認(rèn)為，開發(fā)一種靈敏,、特異的精神分裂癥血液檢測方法還需要更多的標(biāo)記物,。相關(guān)論文發(fā)表在《分子與細(xì)胞蛋白質(zhì)組學(xué)》（Molecular & Cellular Proteomics）上。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
