Primary membranous nephropathy (MN) is an autoimmune glomerular disease in which autoantibodies are directed against podocyte proteins. In about 80% of cases the main targeted antigen is the phospholipase A2 receptor 1 (PLA2R1). Anti-PLA2R1 antibodies are mainly immunoglobulin G type 4 (IgG4). However, the antigenic target remains to be defined in 20% of cases. MN can be associated with chronic inflammatory demyelinating polyneuropathy, an autoimmune disease of the peripheral nervous system where a common antigenic target has yet to be identified. To ascertain a possible novel target antigen, we analyzed kidney biopsies from five patients positive for anti-contactin 1 antibodies and presenting with MN combined with chronic inflammatory demyelinating polyneuropathy. Eluted IgG from biopsy sections against contactin 1 and nerve tissue were screened. Western blot revealed contactin 1 expression in normal kidney glomeruli. Confocal microscopic analysis showed the presence and colocalization of contactin 1 and IgG4 on the glomerular basement membrane of these patients. Glomerular contactin 1 was absent in patients with anti–PLA2R1-associated MN or membranous lupus nephritis or a healthy control. The eluted IgG from contactin 1–positive biopsy sections but not the IgG eluted from patients with PLA2R1 MN bound contactin 1 with the main eluted subclass IgG4. Eluted IgG could bind paranodal tissue (myelinated axon) and colocalized with commercial anti-contactin 1 antibody. Thus, contactin 1 is a novel common antigenic target in MN associated with chronic inflammatory demyelinating polyneuropathy. However, the precise pathophysiology remains to be elucidated.

原发性膜性肾病 (MN) 是一种自身免疫性肾小球疾病，其中自身抗体针对足细胞蛋白。在大约 80% 的情况下，主要的靶向抗原是磷脂酶 A2 受体 1 (PLA2R1)。抗PLA2R1抗体主要是免疫球蛋白G 4型（IgG4）。然而，仍有 20% 的病例的抗原靶点有待确定。MN 可能与慢性炎症性脱髓鞘性多发性神经病有关，这是一种周围神经系统的自身免疫性疾病，其共同的抗原靶点尚未确定。为了确定可能的新靶抗原，我们分析了来自 5 名抗接触蛋白 1 抗体阳性并表现为 MN 合并慢性炎症性脱髓鞘性多发性神经病的患者的肾活检。筛选来自活检切片的针对接触蛋白 1 和神经组织的洗脱 IgG。Western印迹显示正常肾小球中的contactin 1表达。共聚焦显微镜分析显示这些患者的肾小球基底膜上存在接触蛋白 1 和 IgG4 并共定位。抗 PLA2R1 相关 MN 或膜性狼疮肾炎患者或健康对照患者中不存在肾小球接触蛋白 1。从接触蛋白 1 阳性活检切片中洗脱的 IgG 但不是从 PLA2R1 MN 患者中洗脱的 IgG 结合接触蛋白 1 与主要洗脱的 IgG4 亚类。洗脱的 IgG 可以结合结节旁组织（有髓轴突）并与商业抗接触蛋白 1 抗体共定位。因此，contactin 1 是与慢性炎症性脱髓鞘性多发性神经病相关的 MN 中一种新的常见抗原靶点。然而，确切的病理生理学仍有待阐明。