Neural cell adhesion molecule 1 is a novel autoantigen in membranous lupus nephritis

Caza, Tiffany; Hassen, Samar; Kuperman, Michael; Sharma, Smriti; Dvanajscak, Zeljko; Arthur, John M.; Edmondson, Rick D.; Storey, Aaron J.; Herzog, Christian; Kenan, Daniel J.; Larsen, Christopher P.

doi:10.1016/j.kint.2020.09.016

Cited by 115 publications

(106 citation statements)

References 26 publications

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“…Neural cell adhesion molecule 1 has been detected in both primary MN and membranous lupus nephritis. 37 Our MS/MS data also confirms the finding of neural cell adhesion molecule 1 in approximately 2%-4% of patients with primary MN and membranous lupus nephritis (unpublished data). Another potential antigen, high temperature requirement protein A1 has also been recently described in MN.…”

Section: Other Potential Mn Antigenssupporting

confidence: 88%

New ‘Antigens’ in Membranous Nephropathy

Sethi

2020

JASN

173

128

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Membranous nephropathy (MN) occurs due to deposition of immune complexes along the subepithelial region of glomerular basement membrane. Two previously identified target antigens for the immune complexes, PLA2R (identified in 2009) and THSD7A (in 2014), account for approximately 60% of all MN, both primary and secondary. In the remaining MN, target antigens were unknown. Use of laser microdissection and mass spectrometry enabled identification of new “antigens.” This approach led to the identification of four novel types of MN: exotosin 1 (EXT1)– and exotosin 2 (EXT2)–associated MN, NELL1-associated MN, Sema3B-associated MN, and PCDH7-associated MN. Each of these represents a distinct disease entity, with different clinical and pathologic findings. In this review, the structure of the proteins and the clinical and pathologic findings of the new types of MN are discussed. The role of mass spectrometry for accurate diagnosis of MN cannot be overemphasized. Finally, any classification of MN should be made on the basis of the antigens that are detected. Further studies are required to understand the pathophysiology, response to treatment, and outcomes of these new MNs.

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Section: Other Potential Mn Antigenssupporting

confidence: 88%

New ‘Antigens’ in Membranous Nephropathy

Sethi

2020

JASN

173

128

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“…NCAM1, a member of the Ig superfamily of proteins (MW, 120 kDa), was identified by Larsen's group [ 13 ▪▪ ] using the same approach as Sethi et al but in addition they performed protein G immunoprecipitation studies from frozen biopsies. NCAM1 was found to colocalize with IgG within glomerular immune deposits.…”

Section: Neural Cell Adhesion Molecule 1: a ’New’ Antigen Also Associmentioning

confidence: 99%

“…Neuropsychiatric disease occurred in 8/20 (40%) patients possibly related to NCAM1 expression in the central nervous system [ 15 ]. Unexpectedly, it could not be detected in podocytes in normal kidney biopsies or non-NCAM1 membranous nephropathy [ 13 ▪▪ ].…”

Section: Neural Cell Adhesion Molecule 1: a ’New’ Antigen Also Associmentioning

confidence: 99%

Membranous nephropathy: current understanding of various causes in light of new target antigens

Ronco

Dębiec

2021

Current Opinion in Nephrology &Amp; Hypertension

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Purpose of review Membranous nephropathy is an autoimmune disease caused by antibodies mostly directed to podocyte antigens. PLA2R and THSD7A antigens were described in 2009 and 2014 using classical immunochemical techniques. In the last 2 years, thanks to the combination of laser microdissection of glomeruli and mass spectrometry of solubilized digested proteins, several antigens associated with various causes have been described in patients with membranous nephropathy. The purpose of this review is to report on those “new” antigens and to analyse the clinicopathological correlations that make each of this antigen unique. Recent findings This article covers the literature of the last 2 years devoted to the description of those new antigens and biomarkers including NELL-1 and Semaphorin 3B in primary membranous nephropathy, and exostosins 1 and 2 and NCAM in lupus class V membranous nephropathy, which will be compared with the previously described antigens. These findings will lead to propose a new classification of membranous nephropathy based on serology and tissue antigen identification that could/should substitute for the classical distinction between primary and secondary membranous nephropathy. Summary The discovery of the latest antigens has major implications for the care of patients with membranous nephropathy as they drive the etiologic investigations and provide invaluable markers for treatment monitoring.

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“…However, so far, circulating autoantibodies to exostosin1/exostosin2 have not been validated. Caza et al identified neural cell adhesion molecule 1 (NCAM1) as a membranous antigen by mass spectrometry analysis [ 17 ]. Patients with NCAM1-positive IMN were followed to identify whether they developed lupus, which is important in determining whether NCAM1-positive or anti-NCAM1 antibodies can be a precursor to SLE [ 17 ].…”

Section: New Diagnostic Biomarkersmentioning

confidence: 99%

“…Caza et al identified neural cell adhesion molecule 1 (NCAM1) as a membranous antigen by mass spectrometry analysis [ 17 ]. Patients with NCAM1-positive IMN were followed to identify whether they developed lupus, which is important in determining whether NCAM1-positive or anti-NCAM1 antibodies can be a precursor to SLE [ 17 ]. In recent years, increasing attention has been paid to the role of the complement system and its regulatory factors in the pathogenesis of IMN.…”

Section: New Diagnostic Biomarkersmentioning

confidence: 99%

A Review of the Current Practice of Diagnosis and Treatment of Idiopathic Membranous Nephropathy in China

Lai

Ling

et al. 2021

Med Sci Monit

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Idiopathic membranous nephropathy (IMN), a common pathological type of nephrotic syndrome, is one of the main causes of kidney failure. With an increasing prevalence, IMN has received considerable attention in China. Based on recent studies, we discuss advances in the diagnosis of IMN and the understanding of its genetic background. Although the pathogenesis of IMN remains unclear, our understanding has been substantially enhanced by the discovery of new antigens such as phospholipase A 2 receptor, thrombospondin type-1 domain-containing 7A, exostosin1/exostosin2, neural epidermal growth factor-like 1 protein, neural cell adhesion molecule 1, semaphorin 3B, and factor H autoantibody. However, due to ethnic, environmental, economic, and lifestyle differences and other factors, a consensus has not yet been reached regarding IMN treatment. In view of the differences between Eastern and Western populations, in-depth clinical evaluations of biomarkers for IMN diagnosis are necessary. This review details the current treatment strategies for IMN in China, including renin-angiotensin system inhibitors, corticosteroid monotherapy, cyclophosphamide, calcineurin inhibitors, mycophenolate mofetil, adrenocorticotropic hormone, and traditional Chinese medicine, as well as biological preparations such as rituximab. In terms of management, the 2012 Kidney Disease Improving Global Outcomes (KDIGO) clinical practice guidelines do not fully consider the characteristics of the Chinese population. Therefore, this review aims to present the current status of IMN diagnosis and treatment in Chinese patients, and includes a discussion of new approaches and remaining clinical challenges.

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Neural cell adhesion molecule 1 is a novel autoantigen in membranous lupus nephritis

Cited by 115 publications

References 26 publications

New ‘Antigens’ in Membranous Nephropathy

New ‘Antigens’ in Membranous Nephropathy

Membranous nephropathy: current understanding of various causes in light of new target antigens

A Review of the Current Practice of Diagnosis and Treatment of Idiopathic Membranous Nephropathy in China

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