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200 例系统性红斑狼疮患者(无论是否合并狼疮肾炎)中抗肾小球基底膜抗体的缺失:GOODLUPUS 研究结果。

Absence of Anti-Glomerular Basement Membrane Antibodies in 200 Patients With Systemic Lupus Erythematosus With or Without Lupus Nephritis: Results of the GOODLUPUS Study.

机构信息

Département de médecine interne, Centre Hospitalier Universitaire de Reims, Reims, France.

Département d'immunologie biologique (laboratoire d'immunologie), Centre Hospitalier Universitaire de Reims, Reims, France.

出版信息

Front Immunol. 2020 Dec 14;11:597863. doi: 10.3389/fimmu.2020.597863. eCollection 2020.

Abstract

INTRODUCTION

Anti-glomerular basement membrane (GBM) antibodies are pathogenic antibodies first detected in renal-limited anti-GBM disease and in Goodpasture disease, the latter characterized by rapidly progressive crescentic glomerulonephritis combined with intra-alveolar hemorrhage. Studies have suggested that anti-GBM antibody positivity may be of interest in lupus nephritis (LN). Moreover, severe anti-GBM vasculitis cases in patients with systemic lupus erythematosus (SLE) have been described in the literature, but few studies have assessed the incidence of anti-GBM antibodies in SLE patients.

OBJECTIVE

The main study objective was to determine if positive anti-GBM antibodies were present in the serum of SLE patients with or without proliferative renal damage and compared to a healthy control group.

METHODOLOGY

This retrospective study was performed on SLE patients' sera from a Franco-German European biobank, developed between 2011 and 2014, from 17 hospital centers in the Haut-Rhin region. Patients were selected according to their renal involvement, and matched by age and gender. The serum from healthy voluntary blood donors was also tested. Anti-GBM were screened by fluorescence enzyme immunoassay (FEIA), and then by indirect immunofluorescence (IIF) in case of low reactivity detection (titer >6 U/ml).

RESULTS

The cohort was composed of 100 SLE patients with proliferative LN (27% with class III, 67% with class IV, and 6% with class V), compared to 100 SLE patients without LN and 100 controls. Patients were mostly Caucasian and met the ACR 1997 criteria and/or the SLICC 2012 criteria. Among the 300 tested sera, no significant levels of anti-GBM antibodies were detected (>10 U/ml) by the automated technique, three sera were found "ambivalent" (>7 U/ml): one in the SLE with LN group and two in the SLE without LN group. Subsequent IIF assays did not detect anti-GBM antibodies.

CONCLUSION

Anti-GBM antibodies were not detected in the serum of Caucasian patients with SLE, even in case of renal involvement, a situation favoring the antigenic exposure of glomerular basement membranes. Our results reaffirm the central role of anti-GBM antibodies as a specific diagnostic biomarker for Goodpasture vasculitis and therefore confirm that anti-GBM antibody must not be carried out in patients with SLE (with or without LN) in the absence of disease-suggestive symptoms.

摘要

简介

抗肾小球基底膜(GBM)抗体是首先在肾脏局限性抗 GBM 疾病和 Goodpasture 病中检测到的致病性抗体,后者的特征是快速进行性新月体性肾小球肾炎合并肺泡内出血。研究表明,抗 GBM 抗体阳性可能与狼疮性肾炎(LN)有关。此外,文献中已描述了系统性红斑狼疮(SLE)患者中严重的抗 GBM 血管炎病例,但很少有研究评估 SLE 患者中抗 GBM 抗体的发生率。

目的

本研究的主要目的是确定是否存在抗 GBM 抗体在有或无增殖性肾损害的 SLE 患者的血清中,并与健康对照组进行比较。

方法

这项回顾性研究是在 2011 年至 2014 年期间在法国-德国欧洲生物库中进行的,来自 Haut-Rhin 地区的 17 家医院中心的 SLE 患者血清中进行的。根据肾脏受累情况选择患者,并按年龄和性别进行匹配。还测试了健康志愿者的血清。通过荧光酶免疫测定(FEIA)筛选抗 GBM,然后在低反应性检测(滴度>6 U/ml)时通过间接免疫荧光(IIF)进行检测。

结果

该队列由 100 例有增殖性 LN 的 SLE 患者组成(27%为 III 级,67%为 IV 级,6%为 V 级),与 100 例无 LN 的 SLE 患者和 100 例对照者进行比较。患者主要为白种人,符合 ACR 1997 标准和/或 SLICC 2012 标准。在 300 例测试血清中,自动化技术未检测到明显水平的抗 GBM 抗体(>10 U/ml),三种血清呈“双阳性”(>7 U/ml):一种在有 LN 的 SLE 组中,两种在无 LN 的 SLE 组中。随后的 IIF 检测未检测到抗 GBM 抗体。

结论

在高加索人 SLE 患者的血清中未检测到抗 GBM 抗体,即使有肾脏受累,这也有利于肾小球基底膜的抗原暴露。我们的结果再次证实了抗 GBM 抗体作为 Goodpasture 血管炎的特异性诊断生物标志物的核心作用,因此证实了在没有疾病提示症状的情况下,抗 GBM 抗体不应该在 SLE 患者(有或无 LN)中进行检测。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a24/7768036/e5a24389851e/fimmu-11-597863-g001.jpg

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