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