胰岛素样生长因子结合蛋白-2 作为狼疮肾炎的生物标志物。

Insulin-like growth factor binding protein-2 as a biomarker for lupus nephritis.

机构信息

Hanoi Medical University, Hanoi, Vietnam.

Vietnam National Children's Hospital, Hanoi, Vietnam.

出版信息

Pediatr Int. 2023 Jan-Dec;65(1):e15613. doi: 10.1111/ped.15613.

DOI:10.1111/ped.15613

PMID:37698235

Abstract

BACKGROUND

Lupus nephritis (LN) is a serious manifestation of systemic lupus erythematosus (SLE). The aim of this study was to identify serum insulin-like growth factor binding protein-2 (IGFBP-2) as a novel non-invasive biomarker for clinical disease and renal pathology in pediatric LN.

METHODS

A cross-sectional study on 93 newly diagnosed LN children who were biopsy-proven, 35 SLE children with no renal involvement as disease controls, and 30 healthy controls (HC) with age and gender-matched. All children were ELISA tested for serum IGFBP-2 levels. Clinical, laboratory, histopathological features of LN patients were collected.

RESULTS

Compared to SLE or HC, serum IGFBP-2 levels were significantly elevated in LN patients. Serum IGFBP-2 could distinguish LN patients from two others (AUC = 0.937, p < 0.001 for LN vs. HC; 0.897, p < 0.0001 for LN vs. SLE). In ROC analysis, IGFBP-2 had a higher ability to differentiate between LN and SLE than anti-dsDNA with AUC values of 0.895 and 0.643, respectively. LN children with systemic lupus erythematosus disease activity index (SLEDAI) in high activity had significantly higher IGFBP-2 concentration than the others with SLEDAI in moderate activity. Serum IGFBP-2 correlated with albuminemia levels (r = 0.415, p < 0.001), urine protein-to-creatinine levels (r = 0.316, p = 0.002), estimated glomerular filtration rate (r = 0.438, p < 0.001), complement C3 (r = 0.333, p = 0.001). More importantly, serum IGFBP-2 correlated with the activity index of renal pathology (r = 0.312, p = 0.007, n = 75).

CONCLUSIONS

Serum IGFBP-2 is a promising biomarker for pediatric lupus nephritis, reflective of disease activity and activity index in renal patients.

摘要

背景

狼疮肾炎 (LN) 是系统性红斑狼疮 (SLE) 的一种严重表现。本研究旨在确定血清胰岛素样生长因子结合蛋白-2 (IGFBP-2) 作为一种新的非侵入性生物标志物，用于儿童 LN 的临床疾病和肾脏病理学。

方法

对 93 例经活检证实的新诊断 LN 儿童进行横断面研究，其中 35 例 SLE 儿童无肾脏受累作为疾病对照，30 例健康对照者与年龄和性别匹配。所有儿童均采用 ELISA 法检测血清 IGFBP-2 水平。收集 LN 患者的临床、实验室、组织病理学特征。

结果

与 SLE 或 HC 相比，LN 患者的血清 IGFBP-2 水平显著升高。血清 IGFBP-2 可将 LN 患者与其他两者区分开（AUC=0.937，p<0.001，LN 与 HC 相比；0.897，p<0.0001，LN 与 SLE 相比）。在 ROC 分析中，IGFBP-2 区分 LN 和 SLE 的能力高于抗 dsDNA，AUC 值分别为 0.895 和 0.643。SLE 疾病活动指数（SLEDAI）高活动的 LN 患儿 IGFBP-2 浓度明显高于 SLEDAI 中活动度中等的患儿。血清 IGFBP-2 与白蛋白水平呈正相关（r=0.415，p<0.001），与尿蛋白/肌酐水平呈正相关（r=0.316，p=0.002），与估算肾小球滤过率呈正相关（r=0.438，p<0.001），与补体 C3 呈正相关（r=0.333，p=0.001）。更重要的是，血清 IGFBP-2 与肾组织病理学活动指数相关（r=0.312，p=0.007，n=75）。