de Seny Dominique, Fillet Marianne, Ribbens Clio, Marée Raphaël, Meuwis Marie-Alice, Lutteri Laurence, Chapelle Jean-Paul, Wehenkel Louis, Louis Edouard, Merville Marie-Paule, Malaise Michel
Laboratory of Rheumatology, GIGA Research, CHU, University of Liège, Liège, Belgium.
Clin Chem. 2008 Jun;54(6):1066-75. doi: 10.1373/clinchem.2007.099549. Epub 2008 Apr 24.
SELDI-TOF mass spectrometry (MS) is a high-throughput proteomic approach with potential for identifying novel forms of serum biomarkers of arthritis.
We used SELDI-TOF MS to analyze serum samples from patients with various forms of inflammatory arthritis. Several protein profiles were collected on different Bio-Rad Laboratories ProteinChip arrays (CM10 and IMAC-Cu(2+)) and were evaluated statistically to select potential biomarkers.
SELDI-TOF MS analyses identified several calgranulin proteins [S100A8 (calgranulin A), S100A9 (calgranulin B), S100A9*, and S100A12 (calgranulin C)], serum amyloid A (SAA), SAA des-Arg (SAA-R), and SAA des-Arg/des-Ser (SAA-RS) as biomarkers and confirmed the results with other techniques, such as western blotting, immunoprecipitation, and nano-LC-MS/MS. The S100 proteins were all able to significantly differentiate samples from patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS) from those of patients with inflammatory bowel diseases used as an inflammatory control (IC) group, whereas the SAA, SAA-R, and SAA-RS proteins were not, with the exception of AS. The 4 S100 proteins were coproduced in all of the pathologies and were significantly correlated with the plasma calprotectin concentration; however, these S100 proteins were correlated with the SAA peak intensities only in the RA and IC patient groups. In RA, these S100 proteins (except for S100A12) were significantly correlated with the serum concentrations of C-reactive protein, matrix metalloproteinase 3, and anti-cyclic citrullinated peptide and with the Disease Activity Score (DAS(28)).
The SELDI-TOF MS technology is a powerful approach for analyzing the status of monomeric, truncated, or posttranslationally modified forms of arthritis biomarkers, such as the S100A8, S100A9, S100A12, and SAA proteins. The fact that the SELDI-TOF MS data were correlated with results obtained with the classic calprotectin ELISA test supports the reliability of this new proteomic technique.
表面增强激光解吸/电离飞行时间质谱（SELDI-TOF MS）是一种高通量蛋白质组学方法，具有识别关节炎血清生物标志物新形式的潜力。
我们使用SELDI-TOF MS分析各种炎症性关节炎患者的血清样本。在不同的伯乐公司蛋白质芯片阵列（CM10和IMAC-Cu(2+)）上收集了几种蛋白质谱，并进行统计学评估以选择潜在的生物标志物。
SELDI-TOF MS分析鉴定出几种钙粒蛋白 [S100A8（钙粒蛋白A）、S100A9（钙粒蛋白B）、S100A9* 和 S100A12（钙粒蛋白C）]、血清淀粉样蛋白A（SAA）、SAA去精氨酸（SAA-R）和SAA去精氨酸/去丝氨酸（SAA-RS）作为生物标志物，并用其他技术（如蛋白质免疫印迹、免疫沉淀和纳升液相色谱-串联质谱）证实了结果。S100蛋白均能够显著区分类风湿关节炎（RA）、银屑病关节炎（PsA）和强直性脊柱炎（AS）患者的样本与用作炎症对照（IC）组的炎症性肠病患者的样本，而SAA、SAA-R和SAA-RS蛋白则不能，AS患者除外。这4种S100蛋白在所有疾病中均共同产生，且与血浆钙卫蛋白浓度显著相关；然而，这些S100蛋白仅在RA和IC患者组中与SAA峰强度相关。在RA中，这些S100蛋白（S100A12除外）与C反应蛋白、基质金属蛋白酶3和抗环瓜氨酸肽的血清浓度以及疾病活动评分（DAS(28)）显著相关。
SELDI-TOF MS技术是分析关节炎生物标志物（如S100A8、S100A9、S100A12和SAA蛋白）的单体、截短或翻译后修饰形式状态的有力方法。SELDI-TOF MS数据与经典钙卫蛋白ELISA检测结果相关这一事实支持了这种新蛋白质组学技术的可靠性。
