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尿半乳糖凝集素 3 结合蛋白(G3BP)作为狼疮性肾炎疾病活动和肾脏病理特征的生物标志物。

Urinary galectin-3 binding protein (G3BP) as a biomarker for disease activity and renal pathology characteristics in lupus nephritis.

机构信息

Department of Rheumatology, Shanghai Institute of Rheumatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University School of Medicine, 145 Shandong (M) Rd, Shanghai, 200001, China.

State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.

出版信息

Arthritis Res Ther. 2022 Mar 28;24(1):77. doi: 10.1186/s13075-022-02763-4.

Abstract

OBJECTIVE

There is an urgent need to identify novel biomarkers of LN to reflect renal histological changes. This study aims to investigate urinary G3BP levels in LN patients and their association with renal disease activity both clinically and pathologically.

METHODS

This is a cross-sectional study. A total of 119 lupus nephritis patients were recruited. Thirty patients with chronic kidney diseases (CKD) and 27 healthy volunteers were also recruited as controls. Urinary G3BP was tested by ELISA. Renal histopathology was reviewed by an experienced renal pathologist. Other clinical variables were collected through chart review.

RESULTS

The levels of uG3BP were significantly increased in active LN patients compared to those in inactive LN (p<0.001), CKD patients (p=0.01), and healthy controls (p<0.001). ROC analysis indicated a good discrimination ability of uG3BP to differentiate active LN from CKD patients (AUC=0.7), inactive LN (AUC=0.76), or healthy controls (AUC=0.87). uG3BP was positively correlated with SLEDAI (ρ=0.352, p<0.001), rSLEDAI (ρ=0.302, p<0.001), and SLICC RAS (ρ=0.465, p<0.001), indicating a role as a biomarker of disease activity. It also correlated with clinical parameters, including 24-h urine protein, ESR, and serum C3 levels. In patients with 24-h urine protein > 3.0 g/24h, uG3BP levels were higher in proliferative LN than in membranous LN (p=0.04). They could discriminate the two pathogenic types of LN (AUC=0.72), and they also positively correlated with AI (ρ=0.389, p=0.008) and scores of hyaline deposits (ρ=0.418, p=0.006). While in patients with 24-h urine protein ≤ 3.0 g/24h, uG3BP levels were not significantly different between proliferative and membranous LN, and there was no apparent relationship between uG3BP levels with AI or with scores of hyaline deposits, but they correlated positively with scores of cellular/fibrocellular crescents (ρ=0.328, p=0.04).

CONCLUSION

uG3BP is a non-invasive biomarker for clinically and histologically reflecting disease activity. It is associated with active histological changes and can be used as a surrogate biomarker when the renal biopsy is impractical.

摘要

目的

迫切需要确定 LN 的新型生物标志物,以反映肾组织学变化。本研究旨在探讨 LN 患者尿液 G3BP 水平及其与临床和病理肾疾病活动的关系。

方法

这是一项横断面研究。共招募了 119 例狼疮肾炎患者。还招募了 30 例慢性肾脏病 (CKD) 患者和 27 名健康志愿者作为对照。通过 ELISA 检测尿 G3BP。由经验丰富的肾脏病理学家对肾组织病理学进行回顾。通过图表回顾收集其他临床变量。

结果

与非活动性 LN 患者 (p<0.001)、CKD 患者 (p=0.01) 和健康对照组 (p<0.001) 相比,活动性 LN 患者的 uG3BP 水平显著升高。ROC 分析表明,uG3BP 区分活动性 LN 与 CKD 患者 (AUC=0.7)、非活动性 LN (AUC=0.76) 或健康对照组 (AUC=0.87) 的能力良好。uG3BP 与 SLEDAI (ρ=0.352,p<0.001)、rSLEDAI (ρ=0.302,p<0.001) 和 SLICC RAS (ρ=0.465,p<0.001) 呈正相关,表明其具有疾病活动的生物标志物作用。它还与包括 24 小时尿蛋白、ESR 和血清 C3 水平在内的临床参数相关。在 24 小时尿蛋白 > 3.0 g/24h 的患者中,增殖性 LN 患者的 uG3BP 水平高于膜性 LN(p=0.04)。它们可以区分两种致病性 LN 类型 (AUC=0.72),并且与 AI(ρ=0.389,p=0.008) 和透明质沉积物评分 (ρ=0.418,p=0.006) 呈正相关。然而,在 24 小时尿蛋白≤3.0 g/24h 的患者中,增殖性和膜性 LN 之间的 uG3BP 水平没有显著差异,uG3BP 水平与 AI 或透明质沉积物评分之间没有明显关系,但与细胞/纤维细胞新月体评分呈正相关 (ρ=0.328,p=0.04)。

结论

uG3BP 是一种非侵入性生物标志物,可用于临床和组织学上反映疾病活动度。它与活跃的组织学变化有关,在进行肾活检不切实际时可用作替代生物标志物。

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