Auto-antibodies to β-F1-ATPase and vimentin in malignant mesothelioma.
Auto-antibodies to β-F1-ATPase and vimentin in malignant mesothelioma.
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DOI：
10.1371/journal.pone.0026515
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Robinson BW
中科院分区：
文献类型：
--
作者：
Creaney J;Dick IM;Yeoman D;Wong S;Robinson BW
恶性间皮瘤(MM)患者产生对MM肿瘤抗原的不明自身抗体。本研究旨在确定多发性骨髓瘤患者自身抗体的靶点，以进一步了解其抗肿瘤反应，并确定这些抗体是否有助于诊断或预测。在免疫印迹筛选策略中使用多发性骨髓瘤患者血清，没有发现共同的免疫反应蛋白。一名长期幸存者的血清识别了五个被测试的MM细胞系中四个的细胞裂解物中存在的50-60 kDa的蛋白质带。对MM细胞系蛋白裂解物进行2D电泳法分离，然后用MALDI TOF质谱仪和多肽质量指纹图分析提取的免疫反应蛋白，鉴定该条带中的免疫活性蛋白。鉴定的免疫反应蛋白是波形蛋白(登录号gi55977767)和三磷酸腺苷合成酶(F1-ATPase)β链(登录号gi114549和gi47606749)。建立了检测这些蛋白抗体的酶联免疫吸附试验。波形蛋白(中位数和95%CI为0.346；MM患者为0.32~0.468，0.327；对照组为0.308~0.428)和肌动蛋白-F1-ATPase(0.257；MM患者为0.221~0.453，0.263；对照组为0.22~0.35)自身抗体水平在MM组和对照组之间均无显著差异。对这些靶点使用二分法抗体水平(高、低)，我们证明了波形蛋白抗体水平与生存无关。相反，与低抗体水平(9个月；p = 0.049)相比，高抗体水平与中位生存期(18个月)显著相关。MM组织芯片免疫组织化学分析显示，33例标本中有28例胞浆表达波形蛋白，14例胞浆表达较强，16例表达较弱。因此，抗波形蛋白抗体和抗-F1-ATPase抗体均不能用于MM的鉴别诊断，但抗-F1-ATPase抗体水平高可能与生存期延长有关，值得进一步研究。
Patients with Malignant Mesothelioma (MM) develop unidentified auto-antibodies to MM tumour antigens. This study was conducted to identify the targets of MM patient auto-antibodies in order to try to understand more of the anti-tumour response and to determine if these antibodies might be helpful for diagnosis or prognostication. Using MM patient sera in a Western immunoblott screening strategy, no common immunoreactive proteins were identified. The sera from one long-term survivor recognised a protein band of 50–60 kDa present in cell lysates from four of five MM cell lines tested. The immunoreactive proteins in this band were identified by 2D electrophoretic separation of a MM cell line protein lysate, followed by analysis of excised immunoreactive proteins on a MALDI TOF mass spectrometer and peptide mass fingerprinting. The immunoreactive proteins identified were vimentin (accession gi55977767) and the ATP synthase (F1-ATPase) beta chain (accession gi114549 and gi47606749). ELISA assays were developed for antibodies to these proteins. Neither vimentin (median and 95% CI 0.346; 0.32–0.468 for MM patients, 0.327; 0.308–0.428 for controls) nor ß-F1-ATPase (0.257; 0.221–0.453 for MM patients, 0.263; 0.22–0.35 for controls) showed significant differences in autoantibody levels between a group of MM patients and controls. Using a dichotomized antibody level (high, low) for these targets we demonstrated that vimentin antibody levels were not associated with survival. In contrast, high ß-F1-ATPase antibody levels were significantly associated with increased median survival (18 months) compared to low ß F1 ATPase antibody levels (9 months; p = 0.049). Immunohistochemical analysis on a MM tissue microarray showed cytoplasmic staining in 28 of 33 samples for vimentin and strong cytoplasmic staining in14 and weak in 16 samples for ß-F1-ATPase. Therefore antibodies to neither vimentin nor ß-F1-ATPase are useful for differential diagnosis of MM, however high antibody levels to ß-F1-ATPase may be associated with increased survival and this warrants further investigation.
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影响因子：
4.7
作者：
Isidoro, A;Casado, E;Cuezva, JM
通讯作者：
Cuezva, JM
DOI：
10.1164/rccm.200907-1020oc
发表时间：
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24.7
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影响因子：
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作者：
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