CN117571991A - 一种评估aosd患者继发mas的生物标志物及其检测试剂盒 - Google Patents
一种评估aosd患者继发mas的生物标志物及其检测试剂盒 Download PDFInfo
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Abstract
本发明涉及一种评估AOSD患者继发MAS的生物标志物及其检测试剂盒，所述生物标志物为PTX3。本发明发现PTX3与AOSD患者疾病活动度呈正相关，对AOSD患者诊断、活动度评价、疗效评估起到标志物的作用，可以作为AOSD患者继发MAS诊断的生物标志物，具有良好的应用前景。
Description
技术领域
本发明属于风湿免疫领域，特别涉及一种评估AOSD患者继发MAS的生物标志物及其检测试剂盒。
背景技术
巨噬细胞激活综合征(MAS)是成人斯蒂尔病(AOSD)的危重并发症，目前缺乏早期识别的生物标志物，迫切需要一种具有高敏感性和特异性的新型生物标志物来改善AOSD继发MAS患者的诊断和评估。五聚体蛋白3(PTX3)是一种急性期蛋白，据报道与许多自身免疫性疾病相关，其血浆水平在炎症与免疫疾病病程早期迅速上升。但是目前还没有PTX3应用于成人斯蒂尔病(AOSD)的相关报道。
发明内容
本发明所要解决的技术问题是提供一种评估AOSD患者继发MAS的生物标志物及其检测试剂盒，PTX3与AOSD患者疾病活动度呈正相关，对AOSD患者诊断、活动度评价、疗效评估起到标志物的作用，可以作为AOSD患者继发MAS诊断的生物标志物，具有良好的应用前景。
本发明提供了一种评估AOSD患者继发MAS的生物标志物，所述生物标志物为PTX3。
所述PTX3与AOSD患者疾病活动度呈正相关。
本发明还提供了一种评估AOSD患者继发MAS的生物标志物的检测试剂盒。
进一步的，所述试剂盒包括用于检测上述生物标志物表达量的试剂。
进一步的，所述试剂盒针对的检测样品为来自受试者的血浆，进行AOSD诊断、活动度评价、疗效评估。
进一步的，所述试剂盒还包括标准品。
有益效果
本发明发现PTX3与AOSD患者疾病活动度呈正相关，对AOSD患者诊断、活动度评价、疗效评估起到标志物的作用，可以作为AOSD患者继发MAS诊断的生物标志物，具有良好的应用前景。
附图说明
图1为AOSD、系统性红斑狼疮、类风湿性关节炎、干燥综合征患者与健康对照的PTX3血浆水平比较；
图2为PTX3在AOSD患者治疗前后的血浆水平比较；
图3为PTX3区分AOSD患者与其他风湿疾病的ROC曲线；
图4为AOSD患者血浆PTX3水平与血沉的相关性；
图5为AOSD患者血浆PTX3水平与C反应蛋白的相关性；
图6为AOSD患者血浆PTX3水平与铁蛋白的相关性；
图7为AOSD患者血浆PTX3水平与系统性评分的相关性；
图8为AOSD患者血浆PTX3水平与HScore的相关性；
图9为AOSD患者未继发MAS与继发MAS血浆PTX3水平比较；
图10为AOSD患者继发MAS、淋巴瘤患者继发噬血细胞综合征、感染患者继发噬血细胞综合征、原发性噬血细胞综合征患者的PTX3血浆水平比较；
图11为PTX3、可溶性白细胞介素2受体、铁蛋白和C反应蛋白区分AOSD患者继发MAS与未继发MAS的ROC曲线比较。
具体实施方式
下面结合具体实施例，进一步阐述本发明。应理解，这些实施例仅用于说明本发明而不用于限制本发明的范围。此外应理解，在阅读了本发明讲授的内容之后，本领域技术人员可以对本发明作各种改动或修改，这些等价形式同样落于本申请所附权利要求书所限定的范围。
实施例1
1.实验方法
检测AOSD患者血浆中的PTX3水平后分析PTX3作为AOSD诊断、活动度评价、疗效评估标志物的作用。并且验证PTX3识别AOSD患者继发MAS的能力。
研究人群：入组152名AOSD患者，包括119名活动期和33名非活动期AOSD患者，144名对照组包括39名系统性红斑狼疮、24名类风湿性关节炎、24名干燥综合征患者和57名健康对照组。所有健康对照组受试者均来自年龄和性别匹配的志愿者，无风湿或其他疾病史。人口统计和临床数据的信息与实验室检查结果一起输入数据库。所有AOSD患者都符合Yamaguchi成人斯蒂尔病标准。AOSD患者的疾病活动性使用改良的Pouchot评分进行评估。如果患者发烧和/或关节痛/关节炎和/或皮肤损伤和/或喉咙痛，则被认为患有活动性AOSD。高疾病活动性患者定义为改良Pouchot评分≥6。患有巨噬细胞活化综合征(MAS)的AOSD患者使用2016年针对MAS合并系统性青少年特发性关节炎(sJIA)的EULAR/ACR/PRINTO分类标准(JIA-MAS标准)进行定义。每个AOSD患者的计算HScore。具有吞噬血淋巴组织细胞增多症(HLH)的淋巴瘤患者、HLH感染患者和原发性HLH患者被定义为符合HLH-2004标准的患者。这项研究是根据赫尔辛基宣言和良好临床实践原则进行的。生物样本是根据中国上海瑞金医院(ID:2016-62)机构研究伦理委员会批准的方案获得的。所有受试者均签署书面知情同意书。
血浆PTX3检测：血浆中的PTX3水平用ELISA试剂盒(购自R&D Systems公司，货号DY1826)进行检测。操作步骤严格按照试剂盒所附说明书执行，然后将检测结果用Rsoftware version 4.2.3软件做统计学分析，用GraphPad Prism 9.0.0软件作图。
2.实验结果
由图1可知，AOSD患者的血浆PTX3水平显着高于健康对照、系统性红斑狼疮、类风湿性关节炎和干燥综合征患者。
由图2-8可知，AOSD患者血浆PTX3水平与炎症标志物、系统性评分和用于评估MAS的评分HScore呈正相关，治疗后AOSD患者PTX3水平显著低于治疗前。
由图9-10可知，继发MAS的活动性AOSD患者PTX3水平升高，显著高于淋巴瘤、感染患者继发噬血细胞综合征以及原发性噬血细胞综合征患者的血浆PTX3水平。
由图11可知，用于识别MAS-AOSD的PTX3曲线下面积值高于噬血细胞综合征生物标志物-可溶性白细胞介素2受体、铁蛋白和C反应蛋白。
3.实验结论
PTX3与AOSD患者疾病活动度呈正相关，对AOSD患者诊断、活动度评价、疗效评估起到标志物的作用，并且可以作为AOSD患者继发MAS诊断的生物标志物。
Claims (6)
1.一种评估AOSD患者继发MAS的生物标志物，其特征在于：所述生物标志物为PTX3。
2.根据权利要求1所述的生物标志物，其特征在于：所述PTX3与AOSD患者疾病活动度呈正相关。
3.一种包含如权利要求1所述的评估AOSD患者继发MAS的生物标志物的检测试剂盒。
4.根据权利要求3所述的试剂盒，其特征在于：所述试剂盒包括用于检测上述生物标志物表达量的试剂。
5.根据权利要求3所述的试剂盒，其特征在于：所述试剂盒针对的检测样品为来自受试者的血浆，进行AOSD诊断、活动度评价、疗效评估。
6.根据权利要求3所述的试剂盒，其特征在于：所述试剂盒还包括标准品。
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