Contactin-1 links autoimmune neuropathy and membranous glomerulonephritis
Fehmi, Janev (University of Oxford)
Davies, Alexander J. (University of Oxford)
Antonelou, Marilina (University College London)
Keddie, Stephen (National Hospital of Neurology and Neurosurgery (Regne Unit))
Pikkupeura, Sonja (University of Oxford)
Querol, Luis (Institut d'Investigació Biomèdica Sant Pau)
Delmont, Emilien (Hospital La Timone (França))
Cortese, Andrea (University of Pavia)
Franciotta, Diego (Mondino Foundation)
Persson, Staffan (Lund University)
Barratt, Jonathan (University of Leicester)
Pepper, Ruth (University College London)
Farinha, Filipa (University College London)
Rahman, Anisur (University College London)
Canetti, Diana (University College London)
Gilbertson, Janet A. (University College London)
Rendell, Nigel B. (University College London)
Radunovic, Aleksandar (Royal London Hospital)
Minton, Thomas (University of Bristol)
Fuller, Geraint (Gloucestershire Royal Hospital)
Murphy, Sinead M. (Tallaght University Hospital & Academic Unit of Neurology (Irlanda))
Carr, Aisling S. (UCL Institute of Neurology (Regne Unit))
Reilly, Mary R. (UCL Institute of Neurology (Regne Unit))
Eftimov, Filip (Amsterdam UMC)
Wieske, Luuk (Amsterdam UMC)
Teunissen, Charlotte E. (Amsterdam UMC)
Roberts, Ian S. D. (John Radcliffe Hospital (Regne Unit))
Ashman, Neil (The Royal London Hospital (Regne Unit))
Salama, Alan D. (University College London Department of Renal Medicine (Regne Unit))
Rinaldi, Simon (University of Oxford)
Universitat Autònoma de Barcelona

Fecha:	2023
Resumen:	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.
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Publicado en:	PloS one, Vol. 18 (march 2023) , ISSN 1932-6203

DOI: 10.1371/journal.pone.0281156
PMID: 36893151

15 p, 1.6 MB

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