Conrad Karsten, Bartsch Holger, Canzler Ulrich, Pilarsky Christian, Grützmann Robert, Bachmann Michael
Institute for Immunology, Technical University Dresden, Dresden, Germany.
Methods Mol Biol. 2010;576:213-30. doi: 10.1007/978-1-59745-545-9_12.
During the development of tumors, autoantibodies against aberrant or overexpressed autoantigens can be induced. Several hundreds of tumor-associated autoantibodies (TAAB) with more or less specificity for tumors have been found until now by molecular cloning and proteomics technologies. Many TAAB are detectable in preclinical stages of the disease and may be indicators of tumor development. The screening for autoantibody responses in tumor patients may lead to new diagnostic tumor markers and may be a simple and effective way to identify concomitantly cytotoxic T-lymphocyte (CTL) reactivity. However, most of the TAAB lack sufficient sensitivity and specificity for use as biomarkers in the clinical practice. For further use TAAB should be selected for their specificity regarding malignancies and for their potential clinical application. If selected for high specificity, for the screening of risk groups the sensitivities of most TAAB are too low. A combined determination of two or more tumor-specific autoantibodies may overcome this problem. Therefore, a further evaluation of the relevance of known autoantibody specificities as well as the search for novel diagnostically relevant TAAB by different methodologies is necessary. An optimal combination of highly specific TAAB in multiparametric assays as well as the standardization of the autoantibody analysis is necessary to exhaust the potential of TAAB in the early (presymptomatic) diagnosis and monitoring of malignancies.
在肿瘤发生发展过程中,可诱导产生针对异常或过表达自身抗原的自身抗体。到目前为止,通过分子克隆和蛋白质组学技术已经发现了数百种对肿瘤具有或多或少特异性的肿瘤相关自身抗体(TAAB)。许多TAAB在疾病的临床前阶段即可检测到,可能是肿瘤发生发展的指标。对肿瘤患者自身抗体反应的筛查可能会产生新的诊断性肿瘤标志物,并且可能是一种识别细胞毒性T淋巴细胞(CTL)反应性的简单有效方法。然而,大多数TAAB在临床实践中用作生物标志物时缺乏足够的敏感性和特异性。为了进一步应用,应根据TAAB对恶性肿瘤的特异性及其潜在的临床应用来进行选择。如果选择具有高特异性的TAAB用于风险人群的筛查,大多数TAAB的敏感性太低。联合检测两种或更多种肿瘤特异性自身抗体可能会克服这个问题。因此,有必要进一步评估已知自身抗体特异性的相关性,并通过不同方法寻找新的具有诊断意义的TAAB。在多参数检测中,高度特异性TAAB的最佳组合以及自身抗体分析的标准化对于充分发挥TAAB在恶性肿瘤早期(症状前)诊断和监测中的潜力是必要的。