European multicentre study validates enhanced liver fibrosis test as biomarker of fibrosis in systemic sclerosis
European multicentre study validates enhanced liver fibrosis test as biomarker of fibrosis in systemic sclerosis
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DOI：
10.1093/rheumatology/key271
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发表时间：
2019-02-01
期刊：
影响因子：
5.5
通讯作者：
Del Galdo, Francesco
中科院分区：
文献类型：
--
作者：
Abignano, Giuseppina;Blagojevic, Jelena;Del Galdo, Francesco
目标.在一个独立的、国际性的、多中心的队列中验证增强型肝纤维化（ELF）试验及其组分--Ⅲ型前胶原氨基末端前肽（PIIINP）、基质金属蛋白酶组织抑制剂-1（TIMP-1）和HA--作为SSc纤维化的生物标志物。254例SSc患者来自6个风湿病中心。根据EUSTAR生物库建议收集和储存血清，并通过自动高通量诊断进行分析。采用SPSS软件进行统计学分析。分析了247例SSc患者（平均年龄55.7 ± 13.9岁，202例女性）。ELF评分、TIMP-1和PIIINP水平在男性（分别为P = 0.0197、P = 0.0107、P = 0.0108）和dcSSc（分别为P = 0.001、P = 0.0008、P < 0.0001）中较高。ELF评分及单项标志物与改良Rodnan皮肤评分显著相关（r = 0.37，P < 0.0001），疾病活动性和严重程度（除HA P = 0.0001外，所有标志物均P <0.0001），与用力肺活量（FVC）%成反比（TIMP-1，r =-0.21，P = 0.0012; PIIINP，r =-0.26，P = 0.0001），TLC%（ELF评分，r =-0.20，P = 0.0036; TIMP-1，r =-0.32，P < 0.0001; PIIINP，r =-0.28，P < 0.0001），肺一氧化碳弥散量（DLCO）%（除HA P = 0.0115外，所有标志物P < 0.0001）。多因素分析显示年龄（P < 0.001）、改良Rodnan皮肤评分（P < 0.001）和DLCO%（P = 0.005）是ELF评分的独立相关因素。在第一次和本验证研究之间，ELF评分作为SSc皮肤和肺受累的独立标志物的价值在457例患者中得到证实。正在进行一项纵向研究，以确定对皮肤和肺部进展具有预测价值的SSc特异性算法。
Objectives. To validate enhanced liver fibrosis (ELF) test and its components-amino-terminal propeptide of procollagen type III (PIIINP), tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) and HA-as biomarkers of fibrosis in SSc in an independent, international, multicentre cohort.Methods. Two hundred and fifty-four SSc patients from six Rheumatology Centres were included. Sera were collected and stored according to EUSTAR biobanking recommendations and analysed through automated high throughput diagnostics. Statistical analysis was performed with SPSS software.Results. Two hundred and forty-seven SSc patients (mean age 55.7 +/- 13.9 years, 202 F) were analysed. ELF score, TIMP-1 and PIIINP levels were higher in males (P = 0.0197, P = 0.0107, P = 0.0108 respectively) and in dcSSc (P = 0.001, P = 0.0008, P < 0.0001 respectively). ELF score and the single markers significantly correlated with modified Rodnan skin score (r = 0.37, P < 0.0001), disease activity and severity (P < 0.0001 for all markers, except for HA P = 0.0001) and inversely with forced vital capacity, (FVC) % (TIMP-1, r = -0.21, P = 0.0012; PIIINP, r = -0.26, P = 0.0001), TLC% (ELF score, r = -0.20, P = 0.0036; TIMP-1, r = -0.32, P < 0.0001; PIIINP, r = -0.28, P < 0.0001), diffusion capacity of the lung for carbon monoxide (DLCO) % (P < 0.0001 for all markers, except for HA P = 0.0115). Multivariate analysis indicated that age (P < 0.001), modified Rodnan skin score (P < 0.001) and DLCO% (P = 0.005) were independently associated with ELF score.Conclusion. Between the first and this validation studies, the value of the ELF score as independent marker of skin and lung involvement in SSc is confirmed in 457 patients. A longitudinal study is on-going to identify an SSc specific algorithm with predictive value for skin and lung progression.