Contactin-1 is a novel target antigen in membranous nephropathy associated with chronic inflammatory demyelinating polyneuropathy

Quintrec, Moglie Le; Teisseyre, Maxime; Bec, Nicole; Delmont, Émilien; Szwarc, Ilan; Perrochia, Hélène; Machet, M.C.; Chauvin, Anthony; Mavroudakis, Nicolas; Taïeb, Guillaume; Lanfranco, Luca; Rigothier, Claire; Boucraut, José; Catalano, Concetta; Geneste, Claire; Pernin, Vincent; Larroque, Christian; Devaux, Jérôme; Beyze, Anaïs

doi:10.1016/j.kint.2021.08.014

Cited by 63 publications

(55 citation statements)

References 24 publications

(36 reference statements)

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“…Serologic assays established for both PLA2R and THSD7A show that circulating autoAb levels correlate to disease activity, are useful for therapeutic monitoring, and inform prognosis (5)(6)(7)(8). Recent studies have identified additional autoantigens or biomarkers implicated in MN, including neural epidermal growth factor-like 1 (9), exostosin 1/2 (10), serine protease HTRA1 (11), neural cell adhesion molecule-1 (12), semaphorin 3B (13), protocadherin 7 (14), transforming growth factor beta receptor 3 (15), and contactin (16).…”

Section: Introductionmentioning

confidence: 99%

The Alternative Pathway Is Necessary and Sufficient for Complement Activation by Anti-THSD7A Autoantibodies, Which Are Predominantly IgG4 in Membranous Nephropathy

Manral

Caza²,

Storey³

et al. 2022

Front. Immunol.

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Membranous nephropathy (MN) is an immune kidney disease characterized by glomerular subepithelial immune complexes (ICs) containing antigen, IgG, and products of complement activation. Whereas proteinuria is caused by complement-mediated podocyte injury, the pathways of complement activation remain controversial due to the predominance of IgG4 in ICs, an IgG subclass considered unable to activate complement. THSD7A, a transmembrane protein expressed on podocytes, is the target autoantigen in ~3% of cases of primary MN. In this study, we analyzed sera from 16 patients with THSD7A-associated MN with regard to the anti-THSD7A IgG subclasses and their ability to fix complement in vitro. The serum concentration of anti-THSD7A IgG varied over two orders of magnitude (1.3-243 μg/mL). As a relative proportion of all IgG anti-THSD7A, IgG4 was by far the most abundant subclass (median 79%), followed by IgG1 (median 11%). IgG4 was the dominant subclass of anti-THSD7A antibodies in 14 sera, while IgG1 was dominant in one and co-dominant in another. One quarter of MN sera additionally contained low levels of anti-THSD7A IgA1. ICs formed by predominantly IgG4 anti-THSD7A autoantibodies with immobilized THSD7A were relatively weak activators of complement in vitro, compared to human IgG1 and IgG3 mAbs used as positive control. Complement deposition on THSD7A ICs was dose-dependent and occurred to a significant extent only at relatively high concentration of anti-THSD7A IgG. C3b fixation by THSD7A ICs was completely abolished in factor B-depleted sera, partially inhibited in C4-depleted sera, unchanged in C1q-depleted sera, and also occurred in Mg-EGTA buffer. These results imply that THSD7A ICs predominantly containing IgG4 activate complement at high IgG4 density, which strictly requires a functional alternative pathway, whereas the classical and lectin pathways are dispensable. These findings advance our understanding of how IgG4 antibodies activate complement.

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Section: Introductionmentioning

confidence: 99%

The Alternative Pathway Is Necessary and Sufficient for Complement Activation by Anti-THSD7A Autoantibodies, Which Are Predominantly IgG4 in Membranous Nephropathy

Manral

Caza²,

Storey³

et al. 2022

Front. Immunol.

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“…In addition to PLA2R1 (60-70% of all MN patients) ( 2 ), the list includes other podocyte antigens such as THSD7A (2-4% of patients) ( 3 ), HTRA1 ( 6 ) and SEMA3B ( 12 ), as well as NELL1 and PCDH7 ( 5 ), which are not expressed by normal podocyes. Finally, a few new antigens are associated with other clinical conditions, such as EXT1/2 ( 13 ), NCAM1 ( 10 ) and TGFBR3 ( 9 ) with lupus nephritis, or CTNTI ( 7 ) with demyelinating polyneuropathy and myositis. The authors also discussed in detail medications, infectious triggers and malignancies and finally suggested the implementation of an antigen-based classification in place of the simplified distinction between primary and secondary MN.…”

Section: Membranous Nephropathymentioning

confidence: 99%

Editorial: Immune dysfunction in nephrotic syndrome - recent advances and new roads ahead

et al. 2022

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“…NCAM-1-related MN mainly manifests as GBM thickening and mesangial proliferation ( Sethi, 2021 ). CNTN1 is a common target antigen with peripheral nerves and podocytes of patients with neurological diseases and MN, and the antibody is mainly immunoglobulin G4 ( Le Quintrec et al, 2021 ). CNTN1 disrupts the adhesion function and normal structure of podocytes by affecting the Notch1 signaling pathway ( Debiec and Ronco, 2021 ).…”

Section: Factors Of Podocyte Injurymentioning

confidence: 99%

Traditional Chinese Medicine in Treating Primary Podocytosis: From Fundamental Science to Clinical Research

Tian

Ren

et al. 2022

Front. Pharmacol.

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Podocytes form a key component of the glomerular filtration barrier. Damage to podocytes is referred to as “podocyte disease.” There are many causes of podocyte injury, including primary injury, secondary injury, and gene mutations. Primary podocytosis mostly manifests as nephrotic syndrome. At present, first-line treatment is based on glucocorticoid administration combined with immunosuppressive therapy, but some patients still progress to end-stage renal disease. In Asia, especially in China, traditional Chinese medicine (TCM) still plays an important role in the treatment of kidney diseases. This study summarizes the potential mechanism of TCM and its active components in protecting podocytes, such as repairing podocyte injury, inhibiting podocyte proliferation, reducing podocyte apoptosis and excretion, maintaining podocyte skeleton structure, and upregulating podocyte-related protein expression. At the same time, the clinical efficacy of TCM in the treatment of primary podocytosis (including idiopathic membranous nephropathy, minimal change disease, and focal segmental glomerulosclerosis) is summarized to support the development of new treatment strategies for primary podocytosis.

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Contactin-1 is a novel target antigen in membranous nephropathy associated with chronic inflammatory demyelinating polyneuropathy

Cited by 63 publications

References 24 publications

The Alternative Pathway Is Necessary and Sufficient for Complement Activation by Anti-THSD7A Autoantibodies, Which Are Predominantly IgG4 in Membranous Nephropathy

The Alternative Pathway Is Necessary and Sufficient for Complement Activation by Anti-THSD7A Autoantibodies, Which Are Predominantly IgG4 in Membranous Nephropathy

Editorial: Immune dysfunction in nephrotic syndrome - recent advances and new roads ahead

Traditional Chinese Medicine in Treating Primary Podocytosis: From Fundamental Science to Clinical Research

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