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1
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Jayanatha K, Kumar A, Sapsford M, Simpson M. Idiopathic membranous nephropathy and synchronous mononeuritis multiplex secondary to idiopathic small vessel vasculitis. BMJ Case Rep 2024; 17:e257762. [PMID: 38423575 PMCID: PMC10910699 DOI: 10.1136/bcr-2023-257762] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/02/2024] Open
Abstract
Membranous nephropathy has been associated with demyelinating polyneuropathies and antiglomerular membrane disease; however, an association with vasculitic neuropathy has not been described. This case describes a patient with biopsy-proven idiopathic membranous nephropathy and synchronous mononeuritis multiplex secondary to idiopathic small vessel vasculitis, who presented with lower limb microvascular ischaemia, peripheral neuropathy and active urinary sediment. Her extensive non-invasive screening for immunological disease and radiological investigations for occult malignancy were unremarkable. The patient received intravenous methylprednisolone and intravenous rituximab induction therapy resulting in complete remission of both the idiopathic membranous nephropathy and small vessel vasculitis at 7 months post treatment.
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Affiliation(s)
- Kalpa Jayanatha
- Medicine, The University of Auckland, Auckland, New Zealand
- Renal Medicine, Middlemore Hospital, Auckland, New Zealand
| | - Ashutosh Kumar
- Renal Medicine, Middlemore Hospital, Auckland, New Zealand
| | - Mark Sapsford
- Rheumatology, Middlemore Hospital, Auckland, New Zealand
| | - Mark Simpson
- Neurology, Auckland City Hospital, Auckland, New Zealand
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Tang Y, Liu J, Gao F, Hao H, Jia Z, Zhang W, Shi X, Liang W, Yu M, Lv H, Tan Y, Li Z, Wang Y, Yuan Y, Meng L, Wang Z. CIDP/autoimmune nodopathies with nephropathy: a case series study. Ann Clin Transl Neurol 2023; 10:706-718. [PMID: 36932648 DOI: 10.1002/acn3.51754] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2022] [Revised: 02/12/2023] [Accepted: 02/16/2023] [Indexed: 03/19/2023] Open
Abstract
OBJECTIVE The co-morbidity of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP)/autoimmune nodopathies with nephropathy has been gradually known in recent years. This study was intended to explore the clinical, serological and neuropathological features of seven patients with CIDP/autoimmune nodopathies and nephropathy. METHODS Among 83 CIDP patients, seven were identified with nephropathy. Their clinical, electrophysiological and laboratory examination data were collected. The nodal/paranodal antibodies were tested. The sural biopsies were performed in all the patients, and renal biopsies were operated in 6 patients. RESULTS Six patients had chronic onsets and one had an acute onset. Four patients exhibited peripheral neuropathy preceding nephropathy while two showed concurrent onset of neuropathy and nephropathy, and one started with nephropathy. All the patients showed demyelination in electrophysiological examination. Nerve biopsies showed mild to moderate mixed neuropathies including demyelinating and axonal changes in all patients. Renal biopsies showed membranous nephropathy in all 6 patients. Immunotherapy was effective in all patients, with two patients showing good response to corticosteroid treatment alone. Four of the patients were positive to anti-CNTN1 antibody. Compared with anti-CNTN1 antibody-negative patients, antibody-positive patients had a higher proportion of ataxia (3/4 vs. 1/3), autonomic dysfunction (3/4 vs. 1/3), less frequent antecedent infections (1/4 vs. 2/3), higher cerebrospinal fluid proteins (3.2 g/L vs. 1.69 g/L), more frequent conduction block on electrophysiological examination (3/4 vs. 1/3), higher myelinated nerve fiber density, and positive CNTN1 expression in the glomeruli of kidney tissues. CONCLUSION Anti-CNTN1 antibody was the most frequent antibody in this group of patients with CIDP/autoimmune nodopathies and nephropathy. Our study suggested that there might be some clinical and pathological differences between the antibody positive and negative patients.
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Affiliation(s)
- Yuwei Tang
- Department of Neurology, Peking University First Hospital, 8 Xishiku Street, Xicheng District, Beijing, 100034, China
| | - Jing Liu
- Department of Neurology, Peking University First Hospital, 8 Xishiku Street, Xicheng District, Beijing, 100034, China
| | - Feng Gao
- Department of Neurology, Peking University First Hospital, 8 Xishiku Street, Xicheng District, Beijing, 100034, China
| | - Hongjun Hao
- Department of Neurology, Peking University First Hospital, 8 Xishiku Street, Xicheng District, Beijing, 100034, China
| | - Zhirong Jia
- Department of Neurology, Peking University First Hospital, 8 Xishiku Street, Xicheng District, Beijing, 100034, China
| | - Wei Zhang
- Department of Neurology, Peking University First Hospital, 8 Xishiku Street, Xicheng District, Beijing, 100034, China
| | - Xin Shi
- Department of Neurology, Peking University First Hospital, 8 Xishiku Street, Xicheng District, Beijing, 100034, China
| | - Wei Liang
- Department of Neurology, Peking University First Hospital, 8 Xishiku Street, Xicheng District, Beijing, 100034, China
| | - Meng Yu
- Department of Neurology, Peking University First Hospital, 8 Xishiku Street, Xicheng District, Beijing, 100034, China
| | - He Lv
- Department of Neurology, Peking University First Hospital, 8 Xishiku Street, Xicheng District, Beijing, 100034, China
| | - Ying Tan
- Department of Nephrology, Peking University First Hospital, 8 Xishiku Street, Xicheng District, Beijing, 100034, China
| | - Zhiying Li
- Department of Nephrology, Peking University First Hospital, 8 Xishiku Street, Xicheng District, Beijing, 100034, China
| | - Yu Wang
- Department of Nephrology, Peking University First Hospital, 8 Xishiku Street, Xicheng District, Beijing, 100034, China
| | - Yun Yuan
- Department of Neurology, Peking University First Hospital, 8 Xishiku Street, Xicheng District, Beijing, 100034, China.,Beijing Key Laboratory of Neurovascular Disease Discovery, Beijing, 100034, China
| | - Lingchao Meng
- Department of Neurology, Peking University First Hospital, 8 Xishiku Street, Xicheng District, Beijing, 100034, China.,Beijing Key Laboratory of Neurovascular Disease Discovery, Beijing, 100034, China
| | - Zhaoxia Wang
- Department of Neurology, Peking University First Hospital, 8 Xishiku Street, Xicheng District, Beijing, 100034, China.,Beijing Key Laboratory of Neurovascular Disease Discovery, Beijing, 100034, China
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3
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Chronic inflammatory demyelinating polyradiculoneuropathy concomitant with nephropathy. Neurol Sci 2022; 43:5885-5898. [DOI: 10.1007/s10072-022-06215-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2022] [Accepted: 06/12/2022] [Indexed: 10/17/2022]
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Salvadori M, Tsalouchos A. Update on New Antigens in the Pathogenesis of Membranous Nephropathy. EUROPEAN MEDICAL JOURNAL 2022. [DOI: 10.33590/emj/22-00130] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
Abstract
Previously, membranous nephropathies were divided into primary and secondary categories when the exact mechanism or pathogenetic factor were unknown.
Approximately 70% accounted for primary membranous nephropathies. The
remaining 30% were called secondary because they developed due to well-known
diseases such as autoimmune diseases, tumours, infections, or drug assumptions.
The discoveries of the M-type phospholipase A2 receptor and of thrombospondin
type 1 domain containing 7A as causative antigens in a part of the so-called primary
membranous nephropathies opened new knowledge on the effective causes of
a large part of these diseases. The availability of novel techniques such as laser
micro-dissection and tandem mass spectrometry, as well as immunochemistry with
antibodies directed against novel proteins, allowed the confirmation of new antigens
involved. The use of confocal microscopy and Western blot allowed detection of the
new antigen on glomerular membrane, and the same antigen and relative antibodies
have been detected in serum samples.
Through these techniques, four new antigens were first detected, including neural
epidermal growth factor 1 and semaphorin 3B in the so-called primary membranous
nephropathy, and exostosin 1 and 2 and neural cell adhesion molecule 1 in lupus
membranous nephropathy.
The aim of this study is to describe the characteristics of the new antigens
discovered and their association with other diseases. In addition, new antigens
are on the horizon, and the story of primary membranous nephropathy is still to be
completely written and understood.
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Affiliation(s)
| | - Aris Tsalouchos
- Division of Nephrology, Santa Maria Annunziata Hospital, Florence, Italy
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Salvadori M, Tsalouchos A. New antigens involved in membranous nephropathy beyond phospholipase A2 receptor. World J Nephrol 2022; 11:115-126. [PMID: 36161266 PMCID: PMC9353762 DOI: 10.5527/wjn.v11.i4.115] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2022] [Revised: 06/24/2022] [Accepted: 07/08/2022] [Indexed: 02/06/2023] Open
Abstract
When the physiopathology of membranous nephropathy was first described, almost 30% of cases were recognized to be secondary to well-known diseases such as autoimmune diseases, tumors or infections. The remaining 70% cases were called primary membranous nephropathy as the exact mechanism or pathogenic factor involved was unknown. The discovery of the M type phospholipase A2 receptor and thrombospondin type 1 domain containing 7A as causative antigens in these "so called" primary membranous nephropathies provided new insights into the effective causes of a large proportion of these cases. Novel techniques such as laser microdissection and tandem mass spectrometry as well as immunochemistry with antibodies directed against novel proteins allowed the confirmation of new involved antigens. Finally, using confocal microscopy to localize these new antigens and immunoglobulin G and Western blot analysis of serum samples, these new antigens were detected on the glomerular membrane, and the related antibodies were detected in serum samples. The same antigens have been recognized in some cases of secondary membranous disease due to autoimmune diseases, tumors and infections. This has allowed examination of the relationship between antigens in primary membranous nephropathy and their presence in some secondary nephropathies. The aim of this study is to describe the characteristics of the new antigens discovered and their association with other diseases.
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Affiliation(s)
- Maurizio Salvadori
- Department of Renal Transplantation, Careggi University Hospital, Florence 50139, Tuscany, Italy
| | - Aris Tsalouchos
- Division of Nephrology, Santa Maria Annunziata, Florence 50012, Tuscany, Italy
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Endmayr V, Tunc C, Ergin L, De Rosa A, Weng R, Wagner L, Yu TY, Fichtenbaum A, Perkmann T, Haslacher H, Kozakowski N, Schwaiger C, Ricken G, Hametner S, Klotz S, Dutra LA, Lechner C, de Simoni D, Poppert KN, Müller GJ, Pirker S, Pirker W, Angelovski A, Valach M, Maestri M, Guida M, Ricciardi R, Frommlet F, Sieghart D, Pinter M, Kircher K, Artacker G, Höftberger R, Koneczny I. Anti-Neuronal IgG4 Autoimmune Diseases and IgG4-Related Diseases May Not Be Part of the Same Spectrum: A Comparative Study. Front Immunol 2022; 12:785247. [PMID: 35095860 PMCID: PMC8795769 DOI: 10.3389/fimmu.2021.785247] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2021] [Accepted: 12/15/2021] [Indexed: 12/18/2022] Open
Abstract
Background IgG4 is associated with two emerging groups of rare diseases: 1) IgG4 autoimmune diseases (IgG4-AID) and 2) IgG4-related diseases (IgG4-RLD). Anti-neuronal IgG4-AID include MuSK myasthenia gravis, LGI1- and Caspr2-encephalitis and autoimmune nodo-/paranodopathies (CNTN1/Caspr1 or NF155 antibodies). IgG4-RLD is a multiorgan disease hallmarked by tissue-destructive fibrotic lesions with lymphocyte and IgG4 plasma cell infiltrates and increased serum IgG4 concentrations. It is unclear whether IgG4-AID and IgG4-RLD share relevant clinical and immunopathological features. Methods We collected and analyzed clinical, serological, and histopathological data in 50 patients with anti-neuronal IgG4-AID and 19 patients with IgG4-RLD. Results A significantly higher proportion of IgG4-RLD patients had serum IgG4 elevation when compared to IgG4-AID patients (52.63% vs. 16%, p = .004). Moreover, those IgG4-AID patients with elevated IgG4 did not meet the diagnostic criteria of IgG4-RLD, and their autoantibody titers did not correlate with their serum IgG4 concentrations. In addition, patients with IgG4-RLD were negative for anti-neuronal/neuromuscular autoantibodies and among these patients, men showed a significantly higher propensity for IgG4 elevation, when compared to women (p = .005). Last, a kidney biopsy from a patient with autoimmune paranodopathy due to CNTN1/Caspr1-complex IgG4 autoantibodies and concomitant nephrotic syndrome did not show fibrosis or IgG4+ plasma cells, which are diagnostic hallmarks of IgG4-RLD. Conclusion Our observations suggest that anti-neuronal IgG4-AID and IgG4-RLD are most likely distinct disease entities.
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Affiliation(s)
- Verena Endmayr
- Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, Vienna, Austria
| | - Cansu Tunc
- Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, Vienna, Austria
| | - Lara Ergin
- Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, Vienna, Austria
| | - Anna De Rosa
- Department of Clinical and Experimental Medicine, Neurology Unit, University of Pisa, Pisa, Italy
| | - Rosa Weng
- Department of Neurology, Medical University of Vienna, Vienna, Austria
| | - Lukas Wagner
- Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, Vienna, Austria
| | - Thin-Yau Yu
- Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, Vienna, Austria
| | - Andreas Fichtenbaum
- Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria
| | - Thomas Perkmann
- Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria
| | - Helmuth Haslacher
- Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria
| | | | - Carmen Schwaiger
- Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, Vienna, Austria
| | - Gerda Ricken
- Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, Vienna, Austria
| | - Simon Hametner
- Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, Vienna, Austria
| | - Sigrid Klotz
- Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, Vienna, Austria
| | - Lívia Almeida Dutra
- Department of Neurology and Neurosurgery, Hospital Israelita Albert Einstein, São Paulo, Brazil
| | - Christian Lechner
- Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, Vienna, Austria
- Pediatric Neurology, Department of Pediatric and Adolescent Medicine, Medical University of Innsbruck, Innsbruck, Austria
| | - Désirée de Simoni
- Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, Vienna, Austria
- Department of Neurology, University Hospital St. Poelten, St. Poelten, Austria
| | - Kai-Nicolas Poppert
- Department of Neurology, Christian Doppler University Hospital, Paracelsus Medical University, Salzburg, Austria
| | - Georg Johannes Müller
- Department of Neurology and Karl Landsteiner Institute for Neuroimmunological and Neurodegenerative Disorders, Klinik Donaustadt, Vienna, Austria
| | - Susanne Pirker
- Department of Neurology, Klinik Hietzing, Vienna, Austria
| | - Walter Pirker
- Department of Neurology, Klinik Ottakring, Vienna, Austria
| | | | - Matus Valach
- Department of Pathology, Klinik Landstrasse, Vienna, Austria
| | - Michelangelo Maestri
- Department of Clinical and Experimental Medicine, Neurology Unit, University of Pisa, Pisa, Italy
| | - Melania Guida
- Department of Clinical and Experimental Medicine, Neurology Unit, University of Pisa, Pisa, Italy
| | - Roberta Ricciardi
- Department of Clinical and Experimental Medicine, Neurology Unit, University of Pisa, Pisa, Italy
| | - Florian Frommlet
- Center for Medical Statistics, Informatics and Intelligent Systems, Section for Medical Statistics, Medical University of Vienna, Vienna, Austria
| | - Daniela Sieghart
- Division of Rheumatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Miklos Pinter
- Wiener Privatklinik – Health Center, Vienna, Austria
| | - Karl Kircher
- Department of Ophthalmology, Medical University of Vienna, Vienna, Austria
| | - Gottfried Artacker
- Department of Pediatrics and Adolescent Medicine, Klinik Donaustadt, Vienna, Austria
| | - Romana Höftberger
- Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, Vienna, Austria
| | - Inga Koneczny
- Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, Vienna, Austria
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Xu Q, Liu S, Zhang P, Wang Z, Chang X, Liu Y, Yan J, He R, Luo X, Zou LY, Chu X, Guo Y, Huang S, Fu X, Huang Y. Characteristics of Anti-Contactin1 Antibody-Associated Autoimmune Nodopathies With Concomitant Membranous Nephropathy. Front Immunol 2021; 12:759187. [PMID: 34675937 PMCID: PMC8523937 DOI: 10.3389/fimmu.2021.759187] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2021] [Accepted: 09/16/2021] [Indexed: 12/13/2022] Open
Abstract
Background The concurrence of anti-contactin 1 (CNTN1) antibody-associated chronic inflammatory demyelinating polyneuropathy (CIDP) and membranous nephropathy (MN) has previously been reported in the literature. CIDP with autoantibodies against paranodal proteins are defined as autoimmune nodopathies (AN) in the latest research. In view of the unclear relationship between CIDP and MN, we performed a case study and literature review to investigate the clinical characteristics of anti-CNTN antibody-associated AN with MN. Methods We detected antibodies against NF155, NF186, CNTN1, CNTN2, CASPR1 and PLA2R in blood samples of a patient with clinically manifested MN and concomitant peripheral neuropathy via double immunofluorescence staining and conducted a quantitative measurement of anti-PLA2R IgG antibodies via enzyme-linked immunosorbent assay (ELISA). Case reports of anti-CNTN1 antibody-associated AN, anti-CNTN1 antibody-associated AN with MN, and CIDP with MN were retrieved through a literature search for a comparative analysis of clinical characteristics. The cases were grouped according to the chronological order of CIDP and MN onset for the comparison of clinical characteristics. Results A 57-year-old man with anti-PLA2R positive MN was admitted to the hospital due to limb numbness, weakness, and proprioceptive sensory disorder. He was diagnosed with anti-CNTN1 antibody-associated AN and recovered well after immunotherapy. Our literature search returned 22 cases of CIDP with MN that occurred before, after, or concurrently with CIDP. Good responses were achieved with early single-agent or combination immunotherapy, but eight out of the 22 patients with CIDP and concomitant MN ultimately developed different motor sequelae. Five patients had anti-CNTN1 antibody-associated AN with MN. Among these patients, males accounted for the majority of cases (male:female=4:1), the mean age at onset was late (60.2 ± 15.7 years, range 43–78 years), and 40% had acute to subacute onset. Clinical manifestations included sensory-motor neuropathy, sensory ataxia caused by proprioceptive impairment, and elevated cerebrospinal fluid protein levels. Conclusion The age at onset of CIDP with MN was earlier than that of anti-CNTN1 antibody-associated AN. MN may occur before, after or concurrently with CIDP. The early detection and isotyping of anti-CNTN1 and anti-PLA2R antibodies and the monitoring of isotype switching may be essential for suspected CIDP patients.
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Affiliation(s)
- Qianhui Xu
- Department of Neurology, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, China
| | - Shuhu Liu
- Department of Research and Development, Guangzhou Weimi Bio-Tech Co., Ltd, Guangzhou, China
| | - Peng Zhang
- Department of Neurology, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, China
| | - Zhen Wang
- Department of Nephrology, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, China
| | - Xin Chang
- Department of Neurology, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, China
| | - Yulu Liu
- Department of Neurology, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, China
| | - Jiahe Yan
- Department of Neurology, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, China
| | - Ruirong He
- Department of Psychiatry, Third Affiliated Hospital of Southern University of Science and Technology, Shenzhen, China
| | - Xiaoguang Luo
- Department of Neurology, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, China
| | - Liang-Yu Zou
- Department of Neurology, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, China
| | - Xiaofan Chu
- Department of Neurology, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, China
| | - Yi Guo
- Department of Neurology, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, China
| | - Suli Huang
- Department of Environment and Health, Shenzhen Center for Disease Control and Prevention, Shenzhen, China
| | - Xuejun Fu
- Department of Neurology, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, China
| | - Ying Huang
- Department of Neurology, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, China
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Mechanisms of Primary Membranous Nephropathy. Biomolecules 2021; 11:biom11040513. [PMID: 33808418 PMCID: PMC8065962 DOI: 10.3390/biom11040513] [Citation(s) in RCA: 38] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2021] [Revised: 03/23/2021] [Accepted: 03/26/2021] [Indexed: 12/11/2022] Open
Abstract
Membranous nephropathy (MN) is an autoimmune disease of the kidney glomerulus and one of the leading causes of nephrotic syndrome. The disease exhibits heterogenous outcomes with approximately 30% of cases progressing to end-stage renal disease. The clinical management of MN has steadily advanced owing to the identification of autoantibodies to the phospholipase A2 receptor (PLA2R) in 2009 and thrombospondin domain-containing 7A (THSD7A) in 2014 on the podocyte surface. Approximately 50–80% and 3–5% of primary MN (PMN) cases are associated with either anti-PLA2R or anti-THSD7A antibodies, respectively. The presence of these autoantibodies is used for MN diagnosis; antibody levels correlate with disease severity and possess significant biomarker values in monitoring disease progression and treatment response. Importantly, both autoantibodies are causative to MN. Additionally, evidence is emerging that NELL-1 is associated with 5–10% of PMN cases that are PLA2R- and THSD7A-negative, which moves us one step closer to mapping out the full spectrum of PMN antigens. Recent developments suggest exostosin 1 (EXT1), EXT2, NELL-1, and contactin 1 (CNTN1) are associated with MN. Genetic factors and other mechanisms are in place to regulate these factors and may contribute to MN pathogenesis. This review will discuss recent developments over the past 5 years.
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Alpaydın Baslo S, İdrisoğlu HA, Aral O, Öge AE. CIDP and membranous nephropathy: a case with limited electrophysiological findings and a rare association. Neurol Sci 2020; 42:367-371. [PMID: 32705488 DOI: 10.1007/s10072-020-04612-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2020] [Accepted: 07/18/2020] [Indexed: 11/24/2022]
Affiliation(s)
- Sezin Alpaydın Baslo
- Department of Neurology, University of Health Sciences Bakirkoy Prof. Dr. Mazhar Osman Training and Research Hospital for Psychiatric, Neurologic, and Neurosurgical Diseases, İstanbul, Turkey.
| | - Halil Atilla İdrisoğlu
- Department of Neurology, Istanbul University Istanbul Faculty of Medicine, Istanbul, Turkey
| | - Orhan Aral
- Department of Internal Medicine, Division of Rheumatology, Istanbul University Istanbul Faculty of Medicine, Istanbul, Turkey
| | - Ali Emre Öge
- Department of Neurology and Neurophysiology, Istanbul University Istanbul Faculty of Medicine, Istanbul, Turkey
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Hashimoto Y, Ogata H, Yamasaki R, Sasaguri T, Ko S, Yamashita K, Xu Z, Matsushita T, Tateishi T, Akiyama S, Maruyama S, Yamamoto A, Kira JI. Chronic Inflammatory Demyelinating Polyneuropathy With Concurrent Membranous Nephropathy: An Anti-paranode and Podocyte Protein Antibody Study and Literature Survey. Front Neurol 2018; 9:997. [PMID: 30538665 PMCID: PMC6277699 DOI: 10.3389/fneur.2018.00997] [Citation(s) in RCA: 44] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2018] [Accepted: 11/05/2018] [Indexed: 12/13/2022] Open
Abstract
Background: Several case reports have described the concurrence of chronic inflammatory demyelinating polyneuropathy (CIDP) and membranous nephropathy (MN). The presence of autoantibodies against podocyte antigens phospholipase A2 receptor (PLA2R) and thrombospondin type 1 domain containing 7A (THSD7A) in MN suggests an autoimmune mechanism. Some CIDP patients also harbor autoantibodies against paranodal proteins such as neurofascin 155 (NF155) and contactin-1 (CNTN1). We investigated the relationship between CIDP and MN by assaying autoantibodies against paranodal and podocyte antigens in a CIDP patient with MN, and by a literature survey on the clinical features of CIDP with MN. Methods: Anti-CNTN1 and NF155 antibodies were measured by flow cytometry using HEK293 cell lines stably expressing human CNTN1 or NF155. Binding capacity of antibodies was validated by immunostaining mouse teased sciatic nerve fibers. Anti-PLA2R antibodies were measured by enzyme-linked sorbent assay and anti-THSD7A antibodies by indirect immunofluorescence assay. Clinical features between 14 CIDP with MN cases including two with anti-CNTN1 antibodies and 20 anti-CNTN1 antibody-positive CIDP cases were compared. Results: A patient whose ages was in the late 70 s complained of progressive weakness and superficial and deep sensory impairment in four extremities over 6 months. Nerve conduction studies showed prominent demyelination patterns. The patient presented with nephrotic syndrome. Renal biopsy disclosed basement membrane thickening with local subepithelial projections and glomerular deposits of IgG4, compatible with MN. Autoantibody assays revealed the presence of IgG4 and IgG1 anti-CNTN1 antibodies, but an absence of anti-NF155, anti-PLA2R, and anti-THSD7A antibodies. The patient's serum stained paranodes of teased sciatic nerves. CIDP with MN and anti-CNTN1 antibody-positive CIDP commonly showed male preponderance, relatively higher age of onset, acute to subacute onset in 35–50% of cases, distal dominant sensorimotor neuropathy, proprioceptive impairment leading to sensory ataxia, and very high cerebrospinal fluid protein levels. However, 11 of 13 CIDP patients with MN had a favorable response to mono- or combined immunotherapies whereas anti-CNTN1 antibody-positive CIDP was frequently refractory to corticosteroids and intravenous immunoglobulin administration. Conclusion: CIDP with MN and anti-CNTN1 antibody-positive CIDP show considerable overlap but are not identical. CIDP with MN is probably heterogeneous and some cases harbor anti-CNTN1 antibodies.
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Affiliation(s)
- Yu Hashimoto
- Department of Neurology, Japan Community Health Care Organization Kyushu Hospital, Fukuoka, Japan
| | - Hidenori Ogata
- Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Ryo Yamasaki
- Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Takakazu Sasaguri
- Department of Pathology, Japan Community Health Care Organization Kyushu Hospital, Fukuoka, Japan
| | - Senri Ko
- Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Kenichiro Yamashita
- Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Zhang Xu
- Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Takuya Matsushita
- Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Takahisa Tateishi
- Department of Neurology, Japan Community Health Care Organization Kyushu Hospital, Fukuoka, Japan
| | - Shin'ichi Akiyama
- Division of Nephrology, Department of Internal Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Shoichi Maruyama
- Division of Nephrology, Department of Internal Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Akifumi Yamamoto
- Department of Neurology, Japan Community Health Care Organization Kyushu Hospital, Fukuoka, Japan
| | - Jun-Ichi Kira
- Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
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11
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Wong AHY, Kokubun N, Fukami Y, Miyaji K, Yuki N. Chronic inflammatory demyelinating polyneuropathy with membranous nephropathy. J Peripher Nerv Syst 2016; 20:63-6. [PMID: 25977098 DOI: 10.1111/jns.12113] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2015] [Revised: 04/12/2015] [Accepted: 04/17/2015] [Indexed: 12/29/2022]
Affiliation(s)
- Anna Hiu Yi Wong
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Norito Kokubun
- Department of Neurology, Dokkyo Medical University, Tochigi, Japan
| | - Yuki Fukami
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Kazuki Miyaji
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Nobuhiro Yuki
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.,Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.,Brain & Mind Research Institute, University of Sydney, Sydney, Sydney, New South Wales, Australia
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12
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Quek AML, Soon D, Chan YC, Thamboo TP, Yuki N. Acute-onset chronic inflammatory demyelinating polyneuropathy with focal segmental glomerulosclerosis. J Neurol Sci 2014; 341:139-43. [PMID: 24726719 DOI: 10.1016/j.jns.2014.03.040] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2013] [Revised: 03/17/2014] [Accepted: 03/20/2014] [Indexed: 12/19/2022]
Abstract
Inflammatory neuropathies have been reported to occur in association with nephrotic syndrome. Their underlying immuno-pathogenic mechanisms remain unknown. A 50-year-old woman concurrently presented with acute-onset chronic inflammatory demyelinating polyneuropathy and nephrotic syndrome secondary to focal segmental glomerulosclerosis. Both neuropathy and proteinuria improved after plasma exchange and steroids. Literature review of cases of concurrent inflammatory neuropathies and nephrotic syndrome revealed similar neuro-renal presentations. This neuro-renal condition may be mediated by autoantibodies targeting myelin and podocytes.
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Affiliation(s)
- Amy May Lin Quek
- Department of Medicine, National University Health System, Singapore
| | - Derek Soon
- Department of Medicine, National University Health System, Singapore
| | - Yee Cheun Chan
- Department of Medicine, National University Health System, Singapore
| | | | - Nobuhiro Yuki
- Department of Medicine, National University Health System, Singapore.
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13
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Filippone EJ, Kanzaria M, Bell R, Newman E, L Farber J. Secondary membranous nephropathy associated with guillain-barré syndrome. CASE REPORTS IN NEPHROLOGY AND UROLOGY 2013; 3:34-9. [PMID: 23626596 PMCID: PMC3636961 DOI: 10.1159/000350903] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
Membranous nephropathy (MN) is one of the most common causes of nephrotic syndrome (NS) in adults. It may be primary, usually mediated by IgG4 anti-phospholipase A2 autoantibodies or secondary to various other conditions. Guillain- Barré syndrome (GBS) has been associated with MN, but a cause and effect relation has not been proven. We present a case of concurrent development of GBS and severe NS, with renal biopsy demonstrating MN. IgG4 stain was negative, indicating that most likely, the MN was secondary and probably caused by the underlying GBS.
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Affiliation(s)
- Edward J Filippone
- Department of Medicine, Thomas Jefferson University, Philadelphia, Pa., USA ; Division of Nephrology, Thomas Jefferson University, Philadelphia, Pa., USA
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14
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Chronic inflammatory demyelinating polyneuropathy and membranous glomerulonephropathy: report of two cases. J Clin Neuromuscul Dis 2012; 3:70-4. [PMID: 19078657 DOI: 10.1097/00131402-200112000-00004] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Chronic inflammatory demyelinating polyneuropathy (CIDP) may develop as an isolated, idiopathic disorder or may occur with a temporal relationship to other systemic disorders. We report two cases of chronic inflammatory demyelinating polyneuropathy and membranous glomerulonephropathy (MGN) occurring in the same patients. In each case, the two disorders manifested in close proximity to each other. These two cases supplement previously reported cases of MGN as a coincident and potentially causally related comorbidity to CIDP. We review previous reports of MGN associated with the full spectrum of inflammatory demyelinating polyneuropathies (IDP).
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15
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Smyth S, Menkes DL. Coincident membranous glomerulonephritis and chronic inflammatory demyelinating polyradiculoneuropathy: Questioning the autoimmunity hypothesis. Muscle Nerve 2008; 37:130-5. [PMID: 17614320 DOI: 10.1002/mus.20841] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Abstract
Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and membranous glomerulonephritis (MGN) are both autoimmune disorders that are rarely observed concurrently. We describe a patient who developed MGN nearly 20 years after the onset of CIDP, resulting in a secondary progression of his neuropathy. He responded dramatically to a novel regimen of plasma exchange and methotrexate. We propose a mechanism other than autoimmunity for the coincidence of these disorders and discuss the theoretical superiority of the treatment regimen that he received.
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Affiliation(s)
- Shane Smyth
- Department of Neurology, University of Tennessee Health Sciences Center at Memphis, 855 Monroe Avenue, Link 415, Memphis, Tennessee 38163, USA
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16
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Chen KH, Chang CT, Hung CC. Glomerulonephritis associated with chronic inflammatory demyelinating polyneuropathy. Ren Fail 2006; 28:255-9. [PMID: 16703799 DOI: 10.1080/08860220600580415] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022] Open
Abstract
Inflammatory polyneuropathies represent an important group of neurological disorders. Review of the literature disclosed that glomerulonephritis seems to be not uncommon in acute inflammatory demyelinating polyneuropathy. On the other hand, glomerulonephritis associated with chronic inflammatory demyelinating polyneuropathy (CIDP) appears to be rare. We herein report a 60-year-old man with a clinical history, physical examination and laboratory investigations consistent with CIDP, who also had severe lower limb edema and proteinuria resistant to medical therapy. Renal biopsy showed features consistent with membranous glomerulonephritis. We review the related literature, and the immunological implications are discussed.
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Affiliation(s)
- Kuan-Hsing Chen
- Department of Nephrology, Chang-Gung Memorial Hospital, Chang-Gung University, Taipei, Taiwan
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17
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Delval A, Stojkovic T, Vermersch P. Relapsing sensorimotor neuropathy with ophthalmoplegia, antidisialosyl antibodies, and extramembranous glomerulonephritis. Muscle Nerve 2006; 33:274-7. [PMID: 16258949 DOI: 10.1002/mus.20452] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
A 72-year-old man presented with oculomotor dysfunction, subacute relapsing sensorimotor neuropathy, elevated erythrocyte sedimentation rate, IgM monoclonal paraprotein, cold agglutinins, and antidisialosyl IgM antibodies, features previously described by the acronym CANOMAD (chronic ataxic neuropathy with ophthalmoplegia, M protein, agglutination, and disialosyl antibodies). The patient also had extramembranous glomerulopathy associated with this syndrome. Treatment with corticosteroids improved both the neuropathy and glomerulopathy. This case suggests that the spectrum of neuropathy associated with monoclonal gammopathy may be broader than originally believed.
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18
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Emsley HCA, Molloy J. Inflammatory demyelinating polyradiculoneuropathy associated with membranous glomerulonephritis and thrombocytopaenia. Clin Neurol Neurosurg 2002; 105:23-6. [PMID: 12445919 DOI: 10.1016/s0303-8467(02)00087-2] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Abstract
A 66-year-old man with secondary progressive multiple sclerosis presented with a flaccid areflexic tetraparesis evolving over a 6-week period. Clinical examination and subsequent investigation confirmed a diagnosis of sub-acute inflammatory demyelinating polyradiculoneuropathy (sub-acute IDP). Nephrotic-range proteinuria and thrombocytopaenia were also noted at the time of presentation-histopathological investigation of the former showed membranous glomerulonephritis as the basis for the protein loss. The IDP, glomerulonephritis and thrombocytopaenia recovered over the same time course. There have been previous reports of either glomerulonephritis or thrombocytopaenia occurring in association with IDP-there are no such reports of all three conditions occurring and resolving simultaneously.
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19
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Henderson RD, Healy HG, McCombe PA, Lander CM. Chronic inflammatory demyelinating polyradiculoneuropathy and severe peripheral oedema: a renal explanation. J Clin Neurosci 2000; 7:148-9. [PMID: 10844803 DOI: 10.1054/jocn.1999.0170] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
Inflammatory demyelinating neuropathies have been associated with membranous and focal sclerosing glomerulonephritis. Here we describe a 58 year old man with a clinical history, physical examination and laboratory investigations consistent with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), who also had severe lower limb and sacral oedema resistant to medical therapy. Mild proteinuria was present and a renal biopsy showed features consistent with focal sclerosing glomerulonephritis (FSGN). The patient's weakness and oedema did not respond to i.v. immunoglobulin or plasmapheresis but responded to high dose oral prednisone. The oedema was not explained by immobility, hypoproteinaemia or local factors. The occurrence of the oedema in a person with CIDP and FSGN and its improvement with prednisone, together with improvement in CIDP and FSGN, suggests that it was immune mediated, possibly due to increased capillary permeability. The presence of renal disease in patients with inflammatory demyelinating neuropathies may be more common than currently realised.
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Affiliation(s)
- R D Henderson
- Department of Neurology, Mayo Clinic, Rochester, USA.
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20
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Panjwani M, Truong LD, Eknoyan G. Membranous glomerulonephritis associated with inflammatory demyelinating peripheral neuropathies. Am J Kidney Dis 1996; 27:279-83. [PMID: 8659507 DOI: 10.1016/s0272-6386(96)90554-5] [Citation(s) in RCA: 26] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
A 55-year-old man with chronic inflammatory demyelinating polyradiculoneuropathy developed the nephrotic syndrome. Renal biopsy showed stage I membranous glomerulonephritis. Review of the literature revealed the association of these two rare syndromes, considered to be due to immunologic dysfunction, in two other cases, as well as several cases of the acute form of demyelinating peripheral polyradiculoneuropathy. The nephrotic syndrome appears to be persistent in the chronic form of the peripheral neuropathy but reversible in its acute form following immunosuppressive therapy. The possibility of a common immunopathogenesis in the association of membranous glomerulonephritis and inflammatory demyelinating peripheral neuropathies deserves further scrutiny.
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Affiliation(s)
- M Panjwani
- Department of Medicine, Baylor College of Medicine, Houston, TX 77030-3498, USA
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21
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Abstract
Membranous nephropathy and multiple sclerosis are believed to be mediated by immune mechanisms. A patient is reported with the first described association of membranous nephropathy and multiple sclerosis. Its significance and possible pathogenetic mechanisms are discussed.
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Affiliation(s)
- A Campos
- Department of Pediatrics, University of South Florida, Tampa 33606
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22
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Fève AP, Smadja D, Rancurel G, Lèger JM. Chronic inflammatory polyneuropathy associated with nephropathy and antifactor VIII antibody: improvement with intravenous immunoglobulin. J Neurol Neurosurg Psychiatry 1992; 55:975-6. [PMID: 1431966 PMCID: PMC1015205 DOI: 10.1136/jnnp.55.10.975-a] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
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23
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Romanick-Schmiedl S, Kiprov DD, Chalmers AC, Miller RG. Extraneural manifestations of chronic inflammatory demyelinating polyradiculoneuropathy. Am J Med 1990; 89:531-4. [PMID: 2220888 DOI: 10.1016/0002-9343(90)90388-t] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Affiliation(s)
- S Romanick-Schmiedl
- Department of Internal Medicine, Children's Hospital of San Francisco, California 94118
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24
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25
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Affiliation(s)
- S B Prusiner
- Department of Neurology, University of California, San Francisco 94143-0518
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