Division of Rheumatology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
Arthritis Res Ther. 2009;11(5):R143. doi: 10.1186/ar2816. Epub 2009 Sep 28.
TNF-like weak inducer of apoptosis (TWEAK) has been implicated as a mediator of chronic inflammatory processes via prolonged activation of the NF-kappaB pathway in several tissues, including the kidney. Evidence for the importance of TWEAK in the pathogenesis of lupus nephritis (LN) has been recently introduced. Thus, TWEAK levels may serve as an indication of LN presence and activity.
Multicenter cohorts of systemic lupus erythematosus (SLE) patients and controls were recruited for cross-sectional and longitudinal analysis of urinary TWEAK (uTWEAK) and/or serum TWEAK (sTWEAK) levels as potential biomarkers of LN. The performance of TWEAK as a biomarker for nephritis was compared with routinely used laboratory tests in lupus patients, including anti-double stranded DNA antibodies and levels of C3 and C4.
uTWEAK levels were significantly higher in LN patients than in non-LN SLE patients and other disease control groups (P = 0.039). Furthermore, uTWEAK was better at distinguishing between LN and non-LN SLE patients than anti-DNA antibodies and complement levels, while high uTWEAK levels predicted LN in SLE patients with an odds ratio of 7.36 (95% confidence interval = 2.25 to 24.07; P = 0.001). uTWEAK levels peaked during LN flares, and were significantly higher during the flare than at 4 and 6 months prior to or following the flare event. A linear mixed-effects model showed a significant association between uTWEAK levels in SLE patients and their disease activity over time (P = 0.008). sTWEAK levels, however, were not found to correlate with the presence of LN or the degree of nephritis activity.
High uTWEAK levels are indicative of LN, as opposed to non-LN SLE and other healthy and disease control populations, and reflect renal disease activity in longitudinal follow-up. Thus, our study further supports a role for TWEAK in the pathogenesis of LN, and provides strong evidence for uTWEAK as a candidate clinical biomarker for LN.
TNF 样凋亡弱诱导物（TWEAK）已被证实可通过延长核因子-κB 通路的激活，在包括肾脏在内的多种组织中作为慢性炎症过程的介质。最近有证据表明 TWEAK 在狼疮肾炎（LN）的发病机制中很重要。因此，TWEAK 水平可作为 LN 存在和活动的指标。
为了进行横断面和纵向分析尿 TWEAK（uTWEAK）和/或血清 TWEAK（sTWEAK）水平作为 LN 的潜在生物标志物，我们招募了多个系统性红斑狼疮（SLE）患者和对照者的多中心队列。将 TWEAK 作为肾炎生物标志物的性能与狼疮患者中常规使用的实验室检测（包括抗双链 DNA 抗体和 C3 和 C4 水平）进行了比较。
LN 患者的 uTWEAK 水平明显高于非 LN SLE 患者和其他疾病对照组（P = 0.039）。此外，与抗 DNA 抗体和补体水平相比，uTWEAK 更能区分 LN 和非 LN SLE 患者，而高 uTWEAK 水平预测 SLE 患者发生 LN 的比值比为 7.36（95%置信区间为 2.25 至 24.07；P = 0.001）。uTWEAK 水平在 LN 发作期间达到峰值，且在发作期间明显高于发作前 4 个月和 6 个月以及发作后 4 个月和 6 个月。线性混合效应模型显示，SLE 患者的 uTWEAK 水平与疾病活动度随时间的变化显著相关（P = 0.008）。然而，sTWEAK 水平与 LN 的存在或肾炎活动程度无关。
高 uTWEAK 水平提示 LN，而不是非 LN SLE 和其他健康和疾病对照组，并在纵向随访中反映肾脏疾病的活动度。因此，我们的研究进一步支持 TWEAK 在 LN 发病机制中的作用，并为 uTWEAK 作为 LN 的候选临床生物标志物提供了有力证据。
