Suttichet Thitima Benjachat, Kittanamongkolchai Wonngarm, Phromjeen Chutipha, Anutrakulchai Sirirat, Panaput Thanachai, Ingsathit Atiporn, Kamanamool Nanticha, Ophascharoensuk Vuddhidej, Sumethakul Vasant, Avihingsanon Yingyos
Department of Medicine, Faculty of Medicine, Center of Excellence in Immunology and Immune-mediated Diseases, Chulalongkorn University, Bangkok, Thailand.
Chula Clinical Research Center and Renal Immunology and Transplantation Research Unit, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Lupus Sci Med. 2019 Apr 9;6(1):e000298. doi: 10.1136/lupus-2018-000298. eCollection 2019.
TNF-like weak inducer of apoptosis (TWEAK) is a proinflammatory molecule that plays a key role in active inflammation of lupus nephritis (LN). Urine TWEAK (uTWEAK) levels were found to be associated with renal disease activity among patients with LN. Here, we determined whether serial measurements of uTWEAK during induction therapy could predict treatment response or not.
Spot urine samples were collected from patients with biopsy-proven active LN at time of flare, and 3 and 6 months after flare to assess the uTWEAK levels. All patients received standard immunosuppressive therapy and treatment response was evaluated at 6 months. The performance of uTWEAK as a predictor for treatment response was compared with clinically used biomarkers for patients with LN.
Among 110 patients with LN, there were 29% complete responders (CR), 34% partial responders (PR) and 37% non-responders (NR). On average, uTWEAK level was consistently low in CR, trended down by 3 months in PR and persistently elevated in NR. uTWEAK levels at month 3 were able to predict complete response at month 6 (OR adjusted for age, sex and creatinine=0.34 [95% CI 0.15 to 0.80], the area under the receiver operating characteristic curve [ROC-AUC]=0.68, p=0.02). The optimal threshold for uTWEAK level at month 3 was 0.46 pg/mgCr, discriminating complete response with 70% sensitivity and 63% specificity. Combining uTWEAK and urine protein at month 3 improved predictive performance for complete response at 6 months (ROC-AUC 0.83, p<0.001).
In addition to urine protein, uTWEAK level at 3 months after flare can improve the accuracy in predicting complete response at 6 months of induction therapy.
肿瘤坏死因子样凋亡微弱诱导剂（TWEAK）是一种促炎分子，在狼疮性肾炎（LN）的活动性炎症中起关键作用。研究发现，LN患者的尿TWEAK（uTWEAK）水平与肾脏疾病活动度相关。在此，我们确定诱导治疗期间对uTWEAK进行连续测量是否能够预测治疗反应。
在病情复发时、复发后3个月和6个月，收集经活检证实为活动性LN患者的随机尿样，以评估uTWEAK水平。所有患者均接受标准免疫抑制治疗，并在6个月时评估治疗反应。将uTWEAK作为治疗反应预测指标的性能与LN患者临床使用的生物标志物进行比较。
110例LN患者中，完全缓解者（CR）占29%，部分缓解者（PR）占34%，无反应者（NR）占37%。平均而言，CR患者的uTWEAK水平始终较低，PR患者在3个月时呈下降趋势，NR患者则持续升高。3个月时的uTWEAK水平能够预测6个月时的完全缓解（校正年龄、性别和肌酐后的OR=0.34[95%CI 0.15至0.80]，受试者工作特征曲线下面积[ROC-AUC]=0.68，p=0.02）。3个月时uTWEAK水平的最佳阈值为0.46 pg/mgCr，区分完全缓解的灵敏度为70%，特异度为63%。将3个月时的uTWEAK和尿蛋白相结合可提高对6个月时完全缓解的预测性能（ROC-AUC 0.83，p<0.001）。
除尿蛋白外，复发后3个月的uTWEAK水平可提高诱导治疗6个月时完全缓解预测的准确性。
