Arkana Laboratories, Little Rock, Arkansas, USA.
Arkana Laboratories, Little Rock, Arkansas, USA.
Kidney Int. 2021 Jul;100(1):171-181. doi: 10.1016/j.kint.2020.09.016. Epub 2020 Oct 9.
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.
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病因。在磷脂酶 A2 受体阳性膜性肾病中已经表明，可以在血清中检测到已知的抗体，靶自身抗原的测定具有诊断意义，可以告知预后，并能够对疾病活动进行非侵入性监测。在这里，我们利用质谱法在福尔马林固定石蜡包埋组织的激光捕获微切割肾小球中进行抗原发现，并在冰冻肾活检组织中进行组织蛋白 G 免疫沉淀研究，以检测免疫复合物。我们发现神经细胞黏附分子 1（NCAM1）是一些膜性狼疮性肾炎病例和罕见的原发性膜性肾病病例的靶抗原。NCAM1 相关性的患病率为膜性狼疮性肾炎病例的 6.6%，原发性膜性肾病病例的 2.0%。通过共聚焦显微镜发现 NCAM1 与 IgG 一起在肾小球免疫沉积物中共定位。此外，来自 NCAM1 相关膜性肾病患者的血清在 Western blot 和间接免疫荧光测定中显示对 NCAM1 重组蛋白的反应性，证明存在循环抗体。因此，我们提出 NCAM1 是膜性狼疮性肾炎患者亚群的靶自身抗原。需要进一步研究以确定抗 NCAM1 抗体水平是否与疾病活动或对治疗的反应相关。
