TNF-α and plasma albumin as biomarkers of disease activity in systemic lupus erythematosus.
TNF-α and plasma albumin as biomarkers of disease activity in systemic lupus erythematosus.
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DOI：
10.1136/lupus-2018-000260
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发表时间：
2018
影响因子：
3.9
通讯作者：
Svenungsson E
中科院分区：
文献类型：
--
作者：
Idborg H;Eketjäll S;Pettersson S;Gustafsson JT;Zickert A;Kvarnström M;Oke V;Jakobsson PJ;Gunnarsson I;Svenungsson E
综合标准/指数目前用于诊断和监测系统性红斑狼疮（SLE）患者。用于这些目的的生物标志物将有助于临床实践。因此，我们评估了大量的细胞因子和基本的实验室检查，并研究了它们作为鉴别剂与对照和作为疾病活动性（DA）生物标志物的性能。我们检查了437例SLE患者，符合美国流变学学会的82项标准，并匹配了322名对照。根据SLE DA指数2000（SLEDAI-2K）和SLE活动性测量（SLAM）评估DA。采用不列颠群岛狼疮活动组（BILAG）评估肾DA。另外，132例患者自我评估其总体疾病活动度（PtGDA）。对空腹EDTA-血浆进行Mesoscale Discovery 30-plex细胞因子测定和常规血液化学。在26种检测的生物标志物中，我们确定TNF-α是SLE患者和对照组之间的上级生物标志物（中位数= 4.5 pg/mL，IQR = 3.1 - 6.2 vs中位数= 2.3 pg/mL，IQR = 2.0 - 2.8）。与SLEDAI-2K和SLAM相关性最强的是TNF-α（分别为斯皮尔曼rho（ρ）= 0.32和ρ = 0.34，部分由肾炎亚组驱动）和p-白蛋白（分别为ρ = − 0.33和ρ = − 0.31）。肾脏受累患者的P-白蛋白降低，TNF-α升高（肾脏BILAG A/B vs C/D/E，p分别为4 × 10 - 16和6 × 10 - 9）。IP-10在关节受累患者中升高（SLAM项目24 ≥ 2 vs ≤ 1，p = 0.0005），但在活动性/非活动性肾脏受累患者中无差异。观察到与PtGDA的最强相关性与p-白蛋白（ρ =-0.42）、IL-6（ρ = 0.30）和TNF-α（ρ = 0.29）有关。根据风湿病学家和患者的评估，TNF-α和p-白蛋白都可以很好地区分SLE患者和对照组，并作为DA的替代品。TNF-α能较好地反映肾DA。我们建议TNF-α和p-白蛋白作为SLE的临床有用的生物标志物值得进一步研究。我们还观察到激活的细胞因子的模式随器官受累而变化。
Composite criteria/indices are presently used to diagnose and monitor patients with systemic lupus erythematosus (SLE). Biomarkers for these purposes would be helpful in clinical practice. We therefore evaluated a large panel of cytokines and basic laboratory tests and investigated their performance as discriminators versus controls and as biomarkers of disease activity (DA). We examined 437 patients with SLE, fulfilling American College of Rheumatology-82 criteria, and 322 matched controls. DA was assessed according to both SLE DA Index 2000 (SLEDAI-2K) and SLE Activity Measure (SLAM). British Isles Lupus Activity Group (BILAG) was used to assess renal DA. Additionally, 132 patients self-assessed their Global Disease Activity (PtGDA). Mesoscale Discovery 30-plex cytokine assay and routine blood chemistry was performed on fasting EDTA-plasma. Of 26 tested biomarkers, we identified TNF-α as the superior discriminator between patients with SLE and controls (median=4.5 pg/mL, IQR=3.1–6.2 vs median=2.3 pg/mL, IQR=2.0–2.8). The strongest correlations to SLEDAI-2K and SLAM were obtained with TNF-α (Spearman rho (ρ)=0.32 and ρ=0.34, respectively), partly driven by the nephritis subgroup, and with p-albumin (ρ=−0.33 and ρ=−0.31, respectively). P-albumin was decreased and TNF-α was increased in patients with kidney involvement (renal BILAG A/B vs C/D/E, p=4×10–16 and p=6×10–9 respectively). IP-10 was increased in patients with joint involvement (SLAM item 24≥2 vs ≤1, p=0.0005) but did not differ when comparing patients with active/inactive kidney involvement. The most powerful correlations to PtGDA was observed with p-albumin (ρ=−0.42), IL-6 (ρ=0.30) and TNF-α (ρ=0.29). TNF-α and p-albumin both performed well as discriminators between patients with SLE and controls and as proxies for DA according to both rheumatologists’ and patients’ assessments. In particular, renal DA was well reflected by TNF-α. We propose that the TNF-α and p-albumin merit further investigations as clinically useful biomarkers in SLE. We also observed that the pattern of activated cytokines varies with organ involvement.
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影响因子：
4.6
作者：
Kong, K. O.;Tan, A. W.;Howe, H. S.
通讯作者：
Howe, H. S.
影响因子：
--
作者：
ADERKA, D;WYSENBEEK, A;WALLACH, D
通讯作者：
WALLACH, D
影响因子：
4.9
作者：
Aringer M;Smolen JS
通讯作者：
Smolen JS
影响因子：
4.9
作者：
Landolt-Marticorena C;Prokopec SD;Morrison S;Noamani B;Bonilla D;Reich H;Scholey J;Avila-Casado C;Fortin PR;Boutros PC;Wither J
通讯作者：
Wither J
影响因子：
13.6
作者：
Friedman, Allon N.;Fadem, Stephen Z.
通讯作者：
Fadem, Stephen Z.