A discrete cluster of urinary biomarkers discriminates between active systemic lupus erythematosus patients with and without glomerulonephritis.
A discrete cluster of urinary biomarkers discriminates between active systemic lupus erythematosus patients with and without glomerulonephritis.
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DOI：
10.1186/s13075-016-1120-0
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发表时间：
2016-10-04
影响因子：
4.9
通讯作者：
Wither J
中科院分区：
文献类型：
--
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
狼疮性肾炎（LN）的管理将大大有助于生物标志物的发现，准确地反映疾病活动的变化。在这里，我们使用蛋白质组学的方法来确定潜在的尿生物标志物与LN。尿液取自60例LN患者配对肾活检，25例活动性非LN SLE患者，24例健康对照。使用Luminex，对128种分析物进行定量并归一化为尿肌酐水平。通过线性建模和非参数统计分析数据，并进行多重比较校正。第二组33例活动性LN、16例活动性非LN和30例缓解期LN SLE患者用于验证结果。与活动性非LN相比，44种分析物在活动性LN中显著增加。这包括许多独特的蛋白质（例如，TIMP-1、派-1、PF 4、vWF和IL-15）以及已知的候选LN生物标志物（例如，脂联素、sVCAM-1和IL-6），其在活动性LN和非LN之间有显著差异（>4倍），所有这些都在验证组中得到证实，并在缓解期LN患者中标准化。这些蛋白质表现出比先前报道的几种生物标志物更强的区分活动性LN和非LN患者的能力。发现10种蛋白质与肾活检的活动评分显著相关，其中8种蛋白质强烈区分活动性增殖性和非增殖性/慢性肾脏病变。确定了许多与活动性肾脏疾病和/或肾活检变化相关的有前景的尿液生物标志物，并且似乎优于许多现有的拟定生物标志物。本文的在线版本（doi：10.1186/s13075-016-1120-0）包含补充材料，可供授权用户使用。
Management of lupus nephritis (LN) would be greatly aided by the discovery of biomarkers that accurately reflect changes in disease activity. Here, we used a proteomics approach to identify potential urinary biomarkers associated with LN. Urine was obtained from 60 LN patients with paired renal biopsies, 25 active non-LN SLE patients, and 24 healthy controls. Using Luminex, 128 analytes were quantified and normalized to urinary creatinine levels. Data were analyzed by linear modeling and non-parametric statistics, with corrections for multiple comparisons. A second cohort of 33 active LN, 16 active non-LN, and 30 remission LN SLE patients was used to validate the results. Forty-four analytes were identified that were significantly increased in active LN as compared to active non-LN. This included a number of unique proteins (e.g., TIMP-1, PAI-1, PF4, vWF, and IL-15) as well as known candidate LN biomarkers (e.g., adiponectin, sVCAM-1, and IL-6), that differed markedly (>4-fold) between active LN and non-LN, all of which were confirmed in the validation cohort and normalized in remission LN patients. These proteins demonstrated an enhanced ability to discriminate between active LN and non-LN patients over several previously reported biomarkers. Ten proteins were found to significantly correlate with the activity score on renal biopsy, eight of which strongly discriminated between active proliferative and non-proliferative/chronic renal lesions. A number of promising urinary biomarkers that correlate with the presence of active renal disease and/or renal biopsy changes were identified and appear to outperform many of the existing proposed biomarkers. The online version of this article (doi:10.1186/s13075-016-1120-0) contains supplementary material, which is available to authorized users.
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影响因子：
--
作者：
Brunner, Hermine I.;Mueller, Michelle;Devarajan, Prasad
通讯作者：
Devarajan, Prasad
影响因子：
2.6
作者：
Abujam, B.;Cheekatla, S. S.;Aggarwal, A.
通讯作者：
Aggarwal, A.
影响因子：
--
作者：
Brunner, Hermine I.;Bennett, Michael R.;Mina, Rina;Suzuki, Michiko;Petri, Michelle;Kiani, Adnan N.;Pendl, Joshua;Witte, David;Ying, Jun;Rovin, Brad H.;Devarajan, Prasad
通讯作者：
Devarajan, Prasad
影响因子：
2.5
作者：
Ayodele, Olugbenga Edward;Okpechi, Ikechi G.;Swanepoel, Charles R.
通讯作者：
Swanepoel, Charles R.
影响因子：
2.5
作者：
MEZZANO, S;BURGOS, ME;MEZZANO, D
通讯作者：
MEZZANO, D