Serum protein profiling of systemic lupus erythematosus and systemic sclerosis using recombinant antibody microarrays.
Serum protein profiling of systemic lupus erythematosus and systemic sclerosis using recombinant antibody microarrays.
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DOI：
10.1074/mcp.m110.005033
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发表时间：
2011-05
期刊：
影响因子：
--
通讯作者：
Wingren C
中科院分区：
文献类型：
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作者：
Carlsson A;Wuttge DM;Ingvarsson J;Bengtsson AA;Sturfelt G;Borrebaeck CA;Wingren C
系统性红斑狼疮（SLE）和系统性硬化症（SSc）是两种严重的自身免疫性结缔组织病。关于其病因的基础知识是有限的，条件显示复杂的发病机制，多方面的介绍，和不可预测的课程。尽管做出了重大努力，但缺乏能够诊断、分类和监测疾病活动的充分验证的生物标志物代表了显著未满足的临床需求。在这项发现研究中，我们首次使用重组抗体微阵列进行SLE和SSc的小型化、多重血清蛋白质谱分析，主要靶向免疫调节蛋白。数据显示，描述了几种候选SLE相关多重血清生物标志物特征，反映了疾病（诊断）、疾病严重程度（表型子集）和疾病活动性。使用正交试验和第二个独立的患者队列验证选择的差异表达标志物。此外，证明了区分SLE与SSc的生物标志物特征，并且观察到的差异随着SLE的严重程度而增加。相比之下，数据显示SSc与健康对照的血清谱更相似。因此，我们已经表明，亲和蛋白质组学可用于去卷积粗，未分级的血清蛋白质组，提取SLE和SSc的分子画像，进一步增强我们对这些复杂的自身免疫性疾病的基本理解。
Systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) are two severe autoimmune connective tissue diseases. The fundamental knowledge about their etiology is limited and the conditions display complex pathogenesis, multifaceted presentations, and unpredictable courses. Despite significant efforts, the lack of fully validated biomarkers enabling diagnosis, classification, and monitoring of disease activity represents significant unmet clinical needs. In this discovery study, we have for the first time used recombinant antibody microarrays for miniaturized, multiplexed serum protein profiling of SLE and SSc, targeting mainly immunoregulatory proteins. The data showed that several candidate SLE-associated multiplexed serum biomarker signatures were delineated, reflecting disease (diagnosis), disease severity (phenotypic subsets), and disease activity. Selected differentially expressed markers were validated using orthogonal assays and a second, independent patient cohort. Further, biomarker signatures differentiating SLE versus SSc were demonstrated, and the observed differences increased with severity of SLE. In contrast, the data showed that the serum profiles of SSc versus healthy controls were more similar. Hence, we have shown that affinity proteomics could be used to de-convolute crude, nonfractionated serum proteomes, extracting molecular portraits of SLE and SSc, further enhancing our fundamental understanding of these complex autoimmune conditions.