粘病毒抗性蛋白A可用于评估干燥综合征患者的疾病活动性
发表者：李常虹
日期：2015-03-04
浏览次数：359
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摘要（芬兰）目的：旨在建立一种简便实用的检测原发性干燥综合征患者（pSS）中I型干扰素（IFN）的生物活性。一半以上的pSS患者中可检测到I型干扰素，且这类患者往往处于高疾病活动度状态。目前多通过检测多种I型IFN诱导基因的表达谱进行评估。
方法：试验的对象为35例pSS患者，应用酶免疫分析法检测粘病毒抗性蛋白A（MxA）水平，并作为评估I型IFN活性的潜在生物指标。应用流式细胞术分离CD14阳性的单核细胞，同时应用流式细胞术检测潜在生物标志分子，如CD64，CD169 和B细胞活化因子(BAFF)的表达情况。应用实时定量PCR的方法检测CD14阳性单核细胞中I型干扰素标志基因—IFI44, IFI44L, IFIT3, LY6E和MX1-表达，进而通过计算IFN评分评估I型干扰素总生物活性。
结果：INF评分与单核细胞和全血中MxA蛋白水平呈强相关(r=0.741, p<0.001)，与CD169 (r=0.495, p<0.001) 和 CD64 (r=0.436, p=0.007)呈弱相关，与BAFF蛋白水平不相关。尤其是全血MxA水平与EULAR的干燥综合征指数评分和多种pSS临床参数相一致。有意思的是部分pSS患者应用了羟氯喹之后出现了MxA水平的下降(EIA, p=0.04; FACS p=0.001)。
结论：MxA实验是一种很好的用于评估pSS患者中I型IFN活性的工具，酶免疫分析法检测MxA最为实用。MxA水平与疾病活动度相关，并且在应用羟氯喹的患者中MxA会下降，说明MxA在根据IFN活性进行分层治疗中的临床实用性。
附原文：ABSTRACT Objective To establish an easy and practical assay for identifying systemic interferon (IFN) type I bioactivity in patients with primary Sjögren’s syndrome ( pSS). The IFN type I signature is present in over half of the pSS patients and identifies a subgroup with a higher disease activity. This signature is currently assessed via laborious expression profiles of multiple IFN type I-inducible genes. Methods In a cohort of 35 pSS patients, myxovirusresistance protein A (MxA) was assessed as a potential biomarker for type I IFN activity, using an enzyme immunoassay (EIA) on whole-blood and flow cytometric analyses (fluorescence-activated cell sorting, FACS) of isolated CD14 monocytes. In addition, potential biomarkers such as CD64, CD169 and B cell-activating factor (BAFF) were simultaneously analysed in CD14 monocytes using FACS. The IFN score, a measure for total type I IFN bioactivity, was calculated using expression values of the IFN type I signature genes— IFI44, IFI44L, IFIT3, LY6E and MX1—in CD14 monocytes, determined by real-time quantitative PCR. Results IFNscores correlated the strongest with monocyte MxA protein (r=0.741, p<0.001) and wholeblood MxA levels (r=0.764, p<0.001), weaker with CD169 (r=0.495, p<0.001) and CD64 (r=0.436, p=0.007), and not at all with BAFF protein. In particular, whole blood MxA levels correlated with EULAR Sjögren’s Syndrome Disease Activity Index scores and numerous clinical pSS parameters. Interestingly, patients on hydroxychloroquine showed reduced MxA levels (EIA, p=0.04; FACS p=0.001). Conclusions The MxA assays were excellent tools to assess IFN type I activity in pSS, MxA-EIA being the most practical. MxA levels associate with features of active disease and are reduced in hydroxychloroquine treated patients, suggesting the clinical applicability of MxA in stratifying patients according to IFN positivity.
引自：Maria NI, Brkic Z, Waris M, et al. MxA as a clinically applicable biomarker for identifying systemic interferon type I in primary Sjögren’s syndrome Ann Rheum Dis Published Online First: [ please include Day Month Year] doi:10.1136/annrheumdis-2012-202552 （注：干燥综合症病人或亲属可加QQ群交流，群号： 118194945 ，本网站站长私人微信号： ssgzz88 ）
方法：试验的对象为35例pSS患者，应用酶免疫分析法检测粘病毒抗性蛋白A（MxA）水平，并作为评估I型IFN活性的潜在生物指标。应用流式细胞术分离CD14阳性的单核细胞，同时应用流式细胞术检测潜在生物标志分子，如CD64，CD169 和B细胞活化因子(BAFF)的表达情况。应用实时定量PCR的方法检测CD14阳性单核细胞中I型干扰素标志基因—IFI44, IFI44L, IFIT3, LY6E和MX1-表达，进而通过计算IFN评分评估I型干扰素总生物活性。
结果：INF评分与单核细胞和全血中MxA蛋白水平呈强相关(r=0.741, p<0.001)，与CD169 (r=0.495, p<0.001) 和 CD64 (r=0.436, p=0.007)呈弱相关，与BAFF蛋白水平不相关。尤其是全血MxA水平与EULAR的干燥综合征指数评分和多种pSS临床参数相一致。有意思的是部分pSS患者应用了羟氯喹之后出现了MxA水平的下降(EIA, p=0.04; FACS p=0.001)。
结论：MxA实验是一种很好的用于评估pSS患者中I型IFN活性的工具，酶免疫分析法检测MxA最为实用。MxA水平与疾病活动度相关，并且在应用羟氯喹的患者中MxA会下降，说明MxA在根据IFN活性进行分层治疗中的临床实用性。
附原文：ABSTRACT Objective To establish an easy and practical assay for identifying systemic interferon (IFN) type I bioactivity in patients with primary Sjögren’s syndrome ( pSS). The IFN type I signature is present in over half of the pSS patients and identifies a subgroup with a higher disease activity. This signature is currently assessed via laborious expression profiles of multiple IFN type I-inducible genes. Methods In a cohort of 35 pSS patients, myxovirusresistance protein A (MxA) was assessed as a potential biomarker for type I IFN activity, using an enzyme immunoassay (EIA) on whole-blood and flow cytometric analyses (fluorescence-activated cell sorting, FACS) of isolated CD14 monocytes. In addition, potential biomarkers such as CD64, CD169 and B cell-activating factor (BAFF) were simultaneously analysed in CD14 monocytes using FACS. The IFN score, a measure for total type I IFN bioactivity, was calculated using expression values of the IFN type I signature genes— IFI44, IFI44L, IFIT3, LY6E and MX1—in CD14 monocytes, determined by real-time quantitative PCR. Results IFNscores correlated the strongest with monocyte MxA protein (r=0.741, p<0.001) and wholeblood MxA levels (r=0.764, p<0.001), weaker with CD169 (r=0.495, p<0.001) and CD64 (r=0.436, p=0.007), and not at all with BAFF protein. In particular, whole blood MxA levels correlated with EULAR Sjögren’s Syndrome Disease Activity Index scores and numerous clinical pSS parameters. Interestingly, patients on hydroxychloroquine showed reduced MxA levels (EIA, p=0.04; FACS p=0.001). Conclusions The MxA assays were excellent tools to assess IFN type I activity in pSS, MxA-EIA being the most practical. MxA levels associate with features of active disease and are reduced in hydroxychloroquine treated patients, suggesting the clinical applicability of MxA in stratifying patients according to IFN positivity.
引自：Maria NI, Brkic Z, Waris M, et al. MxA as a clinically applicable biomarker for identifying systemic interferon type I in primary Sjögren’s syndrome Ann Rheum Dis Published Online First: [ please include Day Month Year] doi:10.1136/annrheumdis-2012-202552 （注：干燥综合症病人或亲属可加QQ群交流，群号： 118194945 ，本网站站长私人微信号： ssgzz88 ）