Contactin-1 links autoimmune neuropathy and membranous glomerulonephritis
(2023) In PLoS ONE 18(3 March).- Abstract
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... (More)
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.
(Less)
- author
- organization
- publishing date
- 2023-03
- type
- Contribution to journal
- publication status
- published
- subject
- in
- PLoS ONE
- volume
- 18
- issue
- 3 March
- article number
- e0281156
- publisher
- Public Library of Science (PLoS)
- external identifiers
-
- pmid:36893151
- scopus:85149719443
- ISSN
- 1932-6203
- DOI
- 10.1371/journal.pone.0281156
- language
- English
- LU publication?
- yes
- id
- 9ea5c728-c160-4130-860d-114b0f366567
- date added to LUP
- 2023-06-09 14:18:33
- date last changed
- 2024-04-19 22:42:07
@article{9ea5c728-c160-4130-860d-114b0f366567,
abstract = {{<p>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.</p>}},
author = {{Fehmi, Janev and Davies, Alexander J. and Antonelou, Marilina and Keddie, Stephen and Pikkupeura, Sonja and Querol, Luis and Delmont, Emilien and Cortese, Andrea and Franciotta, Diego and Persson, Staffan and Barratt, Jonathan and Pepper, Ruth and Farinha, Filipa and Rahman, Anisur and Canetti, Diana and Gilbertson, Janet A. and Rendell, Nigel B. and Radunovic, Aleksandar and Minton, Thomas and Fuller, Geraint and Murphy, Sinead M. and Carr, Aisling S. and Reilly, Mary R. and Eftimov, Filip and Wieske, Luuk and Teunissen, Charlotte E. and Roberts, Ian S.D. and Ashman, Neil and Salama, Alan D. and Rinaldi, Simon}},
issn = {{1932-6203}},
language = {{eng}},
number = {{3 March}},
publisher = {{Public Library of Science (PLoS)}},
series = {{PLoS ONE}},
title = {{Contactin-1 links autoimmune neuropathy and membranous glomerulonephritis}},
url = {{http://dx.doi.org/10.1371/journal.pone.0281156}},
doi = {{10.1371/journal.pone.0281156}},
volume = {{18}},
year = {{2023}},
}