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狼疮性肾炎患者尿液中铜蓝蛋白和单核细胞趋化蛋白-1的水平与毛细血管外增生及慢性损伤相关。

Urinary levels of ceruloplasmin and monocyte chemoattractant protein-1 correlate with extra-capillary proliferation and chronic damage in patients with lupus nephritis.

作者信息

Urrego-Callejas Tomás, Álvarez Simón Sandoval, Arias Luis F, Reyes Blanca Ortiz, Vanegas-García Adriana L, González Luis A, Muñoz-Vahos Carlos H, Vásquez Gloria, Quintana Luis F, Gómez-Puerta José A

机构信息

Grupo de Inmunología Celular e Inmunogenética, Universidad de Antioquia, Medellín, Colombia.

Departamento de Patología, Universidad de Antioquia y Hospital Universitario de San Vicente Fundación, Medellín, Colombia.

出版信息

Clin Rheumatol. 2021 May;40(5):1853-1859. doi: 10.1007/s10067-020-05454-0. Epub 2020 Oct 20.

DOI:10.1007/s10067-020-05454-0
PMID:33079302
Abstract

BACKGROUND AND AIM

There are few studies of urinary biomarkers and histopathologic features in lupus nephritis (LN). The aim was to analyze the correlation between a wide panel of urinary biomarkers and serum concentrations of anti C1q antibodies with histological items of activity and chronicity on kidney biopsy in LN patients.

METHODS

Patients with systemic lupus erythematosus (SLE) according to American College of Rheumatology (ACR) criteria were included. LN diagnosis was based on ACR criteria. Histologic features of activity and chronicity indices were analyzed according to the Austin classification. Serum Anti C1q levels were determined by commercial ELISA. Urinary levels of transferrin, ceruloplasmin (CP), VCAM-1, TWEAK, monocyte chemoattractant protein-1 (MCP-1), neutrophil gelatinase-associated lipocalin (NGAL), and alpha-1-acid glycoprotein were measured by commercial ELISA.

RESULTS

We included 120 SLE patients (81% female, mean age 33.1 ± 9.3 years, 59.4% Mestizo, 37.8% Afro-Latin American): 64% had LN. Kidney biopsy was performed in 55 patients, but only 37 were made in our center. Anti C1q antibodies were associated with endocapillary proliferation. In patients with cellular crescents, urinary concentrations of CP were significantly higher. In patients with a chronicity index (CI) ≥ 4, fibrous crescents, tubular atrophy, and interstitial fibrosis, urinary MCP-1 levels were higher.

CONCLUSIONS

In SLE patients, serum anti C1q antibodies and urinary CP were associated with activity on kidney biopsy and MCP-1 with chronic damage. This panel of biomarkers could be validated in larger, multi-ethnic population as a complementary tool for better stratification of LN patients. Key Points • Urinary biomarkers are complementary useful tools for the assessment of SLE patients. • Urinary levels of CP correlated with activity findings on kidney biopsy in LN patients. • Urinary levels of MCP-1 correlated with chronic damage, especially with fibrous crescents, tubular atrophy, and interstitial fibrosis.

摘要

背景与目的

关于狼疮性肾炎(LN)患者尿液生物标志物和组织病理学特征的研究较少。本研究旨在分析一组广泛的尿液生物标志物以及抗C1q抗体血清浓度与LN患者肾活检组织学活动和慢性病变指标之间的相关性。

方法

纳入符合美国风湿病学会(ACR)标准的系统性红斑狼疮(SLE)患者。LN的诊断基于ACR标准。根据奥斯汀分类法分析活动和慢性病变指标的组织学特征。采用商用酶联免疫吸附测定法(ELISA)测定血清抗C1q水平。通过商用ELISA检测尿液中转铁蛋白、铜蓝蛋白(CP)、血管细胞黏附分子-1(VCAM-1)、肿瘤坏死因子样弱凋亡诱导因子(TWEAK)、单核细胞趋化蛋白-1(MCP-1)、中性粒细胞明胶酶相关脂质运载蛋白(NGAL)和α-1-酸性糖蛋白的水平。

结果

我们纳入了120例SLE患者(81%为女性,平均年龄33.1±9.3岁,59.4%为混血人种,37.8%为非洲裔拉丁美洲人):64%患有LN。55例患者进行了肾活检,但只有37例在我们中心进行。抗C1q抗体与毛细血管内增生相关。在有细胞性新月体的患者中,尿液中CP浓度显著升高。在慢性病变指数(CI)≥4、有纤维性新月体、肾小管萎缩和间质纤维化的患者中,尿液MCP-1水平较高。

结论

在SLE患者中,血清抗C1q抗体和尿液CP与肾活检的活动病变相关,而MCP-1与慢性损伤相关。这组生物标志物可在更大规模的多民族人群中进行验证,作为更好地对LN患者进行分层的辅助工具。要点•尿液生物标志物是评估SLE患者的有用辅助工具。•LN患者尿液中CP水平与肾活检的活动病变结果相关。•尿液中MCP-1水平与慢性损伤相关,尤其是与纤维性新月体、肾小管萎缩和间质纤维化相关。

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