Contactin-1 links autoimmune neuropathy and membranous glomerulonephritis.
Contactin-1 links autoimmune neuropathy and membranous glomerulonephritis.
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DOI：
10.1371/journal.pone.0281156
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发表时间：
2023
期刊：
影响因子：
3.7
通讯作者：
Rinaldi, Simon
中科院分区：
文献类型：
--
作者：
Fehmi, Janev;Davies, Alexander;Antonelou, Marilina;Keddie, Stephen;Pikkupeura, Sonja;Querol, Luis;Delmont, Emilien;Cortese, Andrea;Franciotta, Diego;Persson, Staffan;Barratt, Jonathan;Pepper, Ruth;Farinha, Filipa;Rahman, Anisur A.;Canetti, Diana B.;Gilbertson, Janet;Rendell, Nigel;Radunovic, Aleksandar;Minton, Thomas M.;Fuller, Geraint S.;Murphy, Sinead R.;Carr, Aisling;Reilly, Mary;Eftimov, Filip E.;Wieske, Luuk;Teunissen, Charlotte;Roberts, Ian S. D. D.;Ashman, Neil;Salama, Alan;Rinaldi, Simon
膜性肾小球肾炎（MGN）是成人肾病综合征的常见原因，由肾小球抗体沉积到越来越多的新识别的抗原介导。以前的病例报告表明，抗接触蛋白-1（CNTN 1）介导的神经病变患者与MGN之间存在关联。在一项观察性研究中，我们通过检查CNTN 1抗体与468例疑似免疫介导的神经病变患者、295例特发性MGN患者和256例对照患者的临床特征之间的关系，研究了MGN的病理生物学和这种潜在病因的程度。测定患者IgG、血清CNTN 1抗体和蛋白水平以及免疫复合物沉积的神经元和肾小球结合。我们确定了15例免疫介导的神经病变和并发肾病综合征患者（12/12例活检证实为MGN），以及4例来自特发性MGN队列的分离性MGN患者，所有患者的IgG 4 CNTN 1抗体血清阳性。CNTN 1抗体的患者的肾小球中发现了CNTN 1免疫复合物，但在对照肾脏中没有。通过质谱法在肾小球中鉴定CNTN 1肽。CNTN 1血清阳性患者在很大程度上对一线神经病治疗具有耐药性，但通过递增治疗获得了良好的结局。神经功能和肾功能改善与抑制抗体滴度平行。孤立性MGN无临床神经病变的原因尚不清楚。我们发现，CNTN 1，发现在周围神经和肾小球，是一个共同的目标，自身抗体介导的病理，并可能占1和2%的特发性MGN病例。提高对这种跨系统综合征的认识应有助于早期诊断和更及时地使用有效的治疗。
Membranous glomerulonephritis (MGN) is a common cause of nephrotic syndrome in adults, mediated by glomerular antibody deposition to an increasing number of newly recognised antigens. Previous case reports have suggested an association between patients with anti-contactin-1 (CNTN1)-mediated neuropathies and MGN. In an observational study we investigated the pathobiology and extent of this potential cause of MGN by examining the association of antibodies against CNTN1 with the clinical features of a cohort of 468 patients with suspected immune-mediated neuropathies, 295 with idiopathic MGN, and 256 controls. Neuronal and glomerular binding of patient IgG, serum CNTN1 antibody and protein levels, as well as immune-complex deposition were determined. We identified 15 patients with immune-mediated neuropathy and concurrent nephrotic syndrome (biopsy proven MGN in 12/12), and 4 patients with isolated MGN from an idiopathic MGN cohort, all seropositive for IgG4 CNTN1 antibodies. CNTN1-containing immune complexes were found in the renal glomeruli of patients with CNTN1 antibodies, but not in control kidneys. CNTN1 peptides were identified in glomeruli by mass spectroscopy. CNTN1 seropositive patients were largely resistant to first-line neuropathy treatments but achieved a good outcome with escalation therapies. Neurological and renal function improved in parallel with suppressed antibody titres. The reason for isolated MGN without clinical neuropathy is unclear. We show that CNTN1, found in peripheral nerves and kidney glomeruli, is a common target for autoantibody-mediated pathology and may account for between 1 and 2% of idiopathic MGN cases. Greater awareness of this cross-system syndrome should facilitate earlier diagnosis and more timely use of effective treatment.
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影响因子：
1.6
作者：
Arnold R;Issar T;Krishnan AV;Pussell BA
通讯作者：
Pussell BA
影响因子：
13.6
作者：
Burbelo, Peter D.;Joshi, Megha;Olson, Stephen W.
通讯作者：
Olson, Stephen W.
影响因子：
4.4
作者：
Lux, Anja;Yu, Xiaojie;Nimmerjahn, Falk
通讯作者：
Nimmerjahn, Falk
影响因子：
--
作者：
Jain, Gaurav;Warnock, David G.
通讯作者：
Warnock, David G.
DOI：
10.1093/brain/awx012
发表时间：
2017-04-01
期刊：
Brain : a journal of neurology
影响因子：
--
作者：
Clark AJ;Kaller MS;Galino J;Willison HJ;Rinaldi S;Bennett DLH
通讯作者：
Bennett DLH