Neural cell adhesion molecule 1 is a novel autoantigen in membranous lupus nephritis.
Neural cell adhesion molecule 1 is a novel autoantigen in membranous lupus nephritis.
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DOI：
10.1016/j.kint.2020.09.016
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发表时间：
2021-07
影响因子：
19.6
通讯作者：
Larsen CP
中科院分区：
文献类型：
--
作者：
Caza TN;Hassen SI;Kuperman M;Sharma SG;Dvanajscak Z;Arthur J;Edmondson R;Storey A;Herzog C;Kenan DJ;Larsen CP
膜性狼疮性肾炎是系统性红斑狼疮患者肾病综合征的常见原因。在磷脂酶A2受体阳性膜性肾病中，已知抗体可在血清中检测到，靶自身抗原的测定可具有诊断意义，告知预后，并能够非侵入性监测疾病活动。在这里，我们利用质谱仪的抗原发现在激光捕获的显微切割肾小球福尔马林固定石蜡包埋组织和组织蛋白G免疫沉淀研究，询问免疫复合物从冷冻肾活检组织。我们确定神经细胞粘附分子1（NCAM 1）是膜性狼疮肾炎和罕见的原发性膜性肾病的靶抗原。NCAM 1相关性在膜性狼疮肾炎病例中的患病率为6.6%，在原发性膜性肾病病例中为2.0%。通过共聚焦显微镜发现NCAM 1与IgG在肾小球免疫沉积物内共定位。此外，来自NCAM 1相关膜性肾病患者的血清在Western印迹和间接免疫荧光测定中显示出对NCAM 1重组蛋白的反应性，表明存在循环抗体。因此，我们认为NCAM 1是膜性狼疮性肾炎患者的靶抗原。未来的研究需要确定抗NCAM 1抗体水平是否与疾病活动或对治疗的反应相关。
Membranous lupus nephritis is a frequent cause of nephrotic syndrome in patients with systemic lupus erythematosus. It has been shown in phospholipase A2 receptor positive membranous nephropathy that known antibodies can be detected within sera, determination of the target autoantigen can have diagnostic significance, inform prognosis, and enable non-invasive monitoring of disease activity. Here we utilized mass spectrometry for antigen discovery in laser captured microdissected glomeruli from formalin-fixed paraffin embedded tissue and tissue protein G immunoprecipitation studies to interrogate immune complexes from frozen kidney biopsy tissue. We identified neural cell adhesion molecule 1 (NCAM1) to be a target antigen in some cases of membranous lupus nephritis and within rare cases of primary membranous nephropathy. The prevalence of NCAM1 association was 6.6% of cases of membranous lupus nephritis and in 2.0% of primary membranous nephropathy cases. NCAM1 was found to colocalize with IgG within glomerular immune deposits by confocal microscopy. Additionally, serum from patients with NCAM1-associated membranous nephropathy showed reactivity to NCAM1 recombinant protein on Western blotting and by indirect immunofluorescence assay, demonstrating the presence of circulating antibodies. Thus, we propose that NCAM1 is a target autoantigen in a subset of patients with membranous lupus nephritis. Future studies are needed to determine whether anti-NCAM1 antibody levels correlate with disease activity or response to therapy.
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影响因子：
3.7
作者：
Marković-Lipkovski J;Životić M;Müller CA;Tampe B;Ćirović S;Vještica J;Tomanović N;Zeisberg M;Müller GA
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