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Contactin-1 links autoimmune neuropathy and membranous glomerulonephritis
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 neuropat...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9997925/ https://www.ncbi.nlm.nih.gov/pubmed/36893151 http://dx.doi.org/10.1371/journal.pone.0281156 |
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author | Fehmi, Janev Davies, Alexander J. Antonelou, Marilina Keddie, Stephen Pikkupeura, Sonja Querol, Luis Delmont, Emilien Cortese, Andrea Franciotta, Diego Persson, Staffan Barratt, Jonathan Pepper, Ruth Farinha, Filipa Rahman, Anisur Canetti, Diana Gilbertson, Janet A. Rendell, Nigel B. Radunovic, Aleksandar Minton, Thomas Fuller, Geraint Murphy, Sinead M. Carr, Aisling S. Reilly, Mary R. Eftimov, Filip Wieske, Luuk Teunissen, Charlotte E. Roberts, Ian S. D. Ashman, Neil Salama, Alan D. Rinaldi, Simon |
author_facet | Fehmi, Janev Davies, Alexander J. Antonelou, Marilina Keddie, Stephen Pikkupeura, Sonja Querol, Luis Delmont, Emilien Cortese, Andrea Franciotta, Diego Persson, Staffan Barratt, Jonathan Pepper, Ruth Farinha, Filipa Rahman, Anisur Canetti, Diana Gilbertson, Janet A. Rendell, Nigel B. Radunovic, Aleksandar Minton, Thomas Fuller, Geraint Murphy, Sinead M. Carr, Aisling S. Reilly, Mary R. Eftimov, Filip Wieske, Luuk Teunissen, Charlotte E. Roberts, Ian S. D. Ashman, Neil Salama, Alan D. Rinaldi, Simon |
author_sort | Fehmi, Janev |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-9997925 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-99979252023-03-10 Contactin-1 links autoimmune neuropathy and membranous glomerulonephritis Fehmi, Janev Davies, Alexander J. Antonelou, Marilina Keddie, Stephen Pikkupeura, Sonja Querol, Luis Delmont, Emilien Cortese, Andrea Franciotta, Diego Persson, Staffan Barratt, Jonathan Pepper, Ruth Farinha, Filipa Rahman, Anisur Canetti, Diana Gilbertson, Janet A. Rendell, Nigel B. Radunovic, Aleksandar Minton, Thomas Fuller, Geraint Murphy, Sinead M. Carr, Aisling S. Reilly, Mary R. Eftimov, Filip Wieske, Luuk Teunissen, Charlotte E. Roberts, Ian S. D. Ashman, Neil Salama, Alan D. Rinaldi, Simon PLoS One Research Article 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. Public Library of Science 2023-03-09 /pmc/articles/PMC9997925/ /pubmed/36893151 http://dx.doi.org/10.1371/journal.pone.0281156 Text en © 2023 Fehmi et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Fehmi, Janev Davies, Alexander J. Antonelou, Marilina Keddie, Stephen Pikkupeura, Sonja Querol, Luis Delmont, Emilien Cortese, Andrea Franciotta, Diego Persson, Staffan Barratt, Jonathan Pepper, Ruth Farinha, Filipa Rahman, Anisur Canetti, Diana Gilbertson, Janet A. Rendell, Nigel B. Radunovic, Aleksandar Minton, Thomas Fuller, Geraint Murphy, Sinead M. Carr, Aisling S. Reilly, Mary R. Eftimov, Filip Wieske, Luuk Teunissen, Charlotte E. Roberts, Ian S. D. Ashman, Neil Salama, Alan D. Rinaldi, Simon Contactin-1 links autoimmune neuropathy and membranous glomerulonephritis |
title | Contactin-1 links autoimmune neuropathy and membranous glomerulonephritis |
title_full | Contactin-1 links autoimmune neuropathy and membranous glomerulonephritis |
title_fullStr | Contactin-1 links autoimmune neuropathy and membranous glomerulonephritis |
title_full_unstemmed | Contactin-1 links autoimmune neuropathy and membranous glomerulonephritis |
title_short | Contactin-1 links autoimmune neuropathy and membranous glomerulonephritis |
title_sort | contactin-1 links autoimmune neuropathy and membranous glomerulonephritis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9997925/ https://www.ncbi.nlm.nih.gov/pubmed/36893151 http://dx.doi.org/10.1371/journal.pone.0281156 |
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