Urine ALCAM, PF4 and VCAM-1 Surpass Conventional Metrics in Identifying Nephritis Disease Activity in Childhood-Onset Systemic Lupus Erythematosus.
Urine ALCAM, PF4 and VCAM-1 Surpass Conventional Metrics in Identifying Nephritis Disease Activity in Childhood-Onset Systemic Lupus Erythematosus.
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DOI：
10.3389/fimmu.2022.885307
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发表时间：
2022
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
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作者：
儿童期系统性红斑狼疮（cSLE）患者的连续肾活检重复评估和监测狼疮性肾炎（LN）仍然具有挑战性，因此需要非侵入性生物标志物。在这里，我们评估了10种不同性质的尿蛋白标志物，包括细胞因子，趋化因子和粘附分子在区分cSLE疾病活动中的表现。前瞻性入组了84例符合≥4项ACR SLE标准的儿童患者，通过ELISA法对10种蛋白质标志物（即ALCAM、胱抑素-C、血红素结合蛋白、KIM-1、MCP-1、NGAL、PF-4、Timp-1、TWEAK和VCAM-1）进行尿液检测，这些蛋白质标志物标准化为尿肌酐。在免疫抑制开始/递增之前，从活动性肾脏（LN）和活动性非肾脏SLE患者中采集样本。使用SLEDAI-2000评估SLE疾病活动性。59例患者患有临床活动性SLE（SLEDAI评分≥4或有发作），其中29例患者（34.5%）被归类为活动性肾脏，30例患者（35.7%）被归类为活动性非肾脏。25名健康受试者作为对照。活动性LN患者尿ALCAM、KIM-1、PF 4和VCAM-1浓度显著高于活动性非肾性SLE、非活动性SLE和健康对照组。5种尿蛋白仅在2组（血红素结合素、NGAL、MCP 1）或3组（胱抑素-C、TWEAK）之间存在显著差异，在活动性LN患者中检测到最高水平。尿液ALCAM、VCAM-1、PF 4和血液结合素与SLEDAI总评分以及肾脏SLEDAI评分相关性最好（p < 0.05）。尿ALCAM、VCAM-1和血红素结合蛋白优于常规实验室测量（抗dsDNA、补体C3和C4）在确定患者中并发SLE疾病活动性中的作用尿ALCAM、VCAM-1和PF 4是判断cSLE肾脏疾病活动性的最佳指标（AUC分别为0.83、0.88、0.78），超过了常规生物标志物，包括蛋白尿。基于条件概率的无监督贝叶斯网络分析再次证实尿ALCAM是cSLE患者活动性LN的最佳预测因子。尿ALCAM、PF 4和VCAM-1是预测cSLE肾脏疾病活动性的潜在生物标志物，并有可能作为这些患者肾炎发作的替代标志物。
Serial kidney biopsy for repeat evaluation and monitoring of lupus nephritis (LN) in childhood-onset Systemic Lupus Erythematosus (cSLE) remains challenging, thus non-invasive biomarkers are needed. Here, we evaluate the performance of ten urine protein markers of diverse nature including cytokines, chemokines, and adhesion molecules in distinguishing disease activity in cSLE. Eighty-four pediatric patients meeting ≥4 ACR criteria for SLE were prospectively enrolled for urine assay of 10 protein markers normalized to urine creatinine, namely ALCAM, cystatin-C, hemopexin, KIM-1, MCP-1, NGAL, PF-4, Timp-1, TWEAK, and VCAM-1 by ELISA. Samples from active renal (LN) and active non-renal SLE patients were obtained prior to onset/escalation of immunosuppression. SLE disease activity was evaluated using SLEDAI-2000. 59 patients had clinically-active SLE (SLEDAI score ≥4 or having a flare), of whom 29 patients (34.5%) were classified as active renal, and 30 patients (35.7%) were active non-renal. Twenty-five healthy subjects were recruited as controls. Urine concentrations of ALCAM, KIM-1, PF4 and VCAM-1 were significantly increased in active LN patients versus active non-renal SLE, inactive SLE and healthy controls. Five urine proteins differed significantly between 2 (hemopexin, NGAL, MCP1) or 3 (Cystatin-C, TWEAK) groups only, with the highest levels detected in active LN patients. Urine ALCAM, VCAM-1, PF4 and hemopexin correlated best with total SLEDAI as well as renal-SLEDAI scores (p < 0.05). Urine ALCAM, VCAM-1 and hemopexin outperformed conventional laboratory measures (anti-dsDNA, complement C3 and C4) in identifying concurrent SLE disease activity among patients (AUCs 0.75, 0.81, 0.81 respectively), while urine ALCAM, VCAM-1 and PF4 were the best discriminators of renal disease activity in cSLE (AUCs 0.83, 0.88, 0.78 respectively), surpassing conventional biomarkers, including proteinuria. Unsupervised Bayesian network analysis based on conditional probabilities re-affirmed urine ALCAM as being most predictive of active LN in cSLE patients. Urinary ALCAM, PF4, and VCAM-1 are potential biomarkers for predicting kidney disease activity in cSLE and hold potential as surrogate markers of nephritis flares in these patients.
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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：
2.6
作者：
Balbi, Verena Andrade;Silva, Clovis Artur;Aikawa, Nadia Emi
通讯作者：
Aikawa, Nadia Emi
DOI：
10.1172/jci147334
发表时间：
2022-01-04
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
Chalmers SA;Ayilam Ramachandran R;Garcia SJ;Der E;Herlitz L;Ampudia J;Chu D;Jordan N;Zhang T;Parodis I;Gunnarsson I;Ding H;Shen N;Petri M;Mok CC;Saxena R;Polu KR;Connelly S;Ng CT;Mohan C;Putterman C
通讯作者：
Putterman C
影响因子：
4.9
作者：
Mok CC;Soliman S;Ho LY;Mohamed FA;Mohamed FI;Mohan C
通讯作者：
Mohan C
DOI：
10.1016/j.rdc.2013.05.001
发表时间：
2013-11
期刊：
Rheumatic diseases clinics of North America
影响因子：
--
作者：
Bennett M;Brunner HI
通讯作者：
Brunner HI