The important roles and molecular mechanisms of annexin A <sub>2</sub> autoantibody in children with nephrotic syndrome

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Background

In recent years, B-cell dysfunction has been found to play an important role in the pathogenesis of primary nephrotic syndrome (PNS). B cells play a pathogenic role by secreting antibodies against their target antigens after transforming into plasma cells. Therefore, this study aimed to screen the autoantibodies that cause PNS and explore their pathogenic mechanisms.

Methods

Western blotting and mass spectrometry were employed to screen and identify autoantibodies against podocytes in children with PNS. Both in vivo and in vitro experiments were used to study the pathogenic mechanism of PNS. The results were confirmed in a large multicenter clinical study in children.

Results

Annexin A ₂ autoantibody was highly expressed in children with PNS with a pathological type of minimal change disease (MCD) or focal segmental glomerulosclerosis without genetic factors. The mouse model showed that anti-Annexin A ₂ antibody could induce proteinuria in vivo. Mechanistically, the effect of Annexin A ₂ antibody on the Rho signaling pathway was realized through promoting the phosphorylation of Annexin A ₂ at Tyr24 on podocytes by reducing its binding to PTP1B, which led to the cytoskeletal rearrangement and damage of podocytes, eventually causing proteinuria and PNS.

Conclusions

Annexin A ₂ autoantibody may be responsible for some cases of PNS with MCD/FSGS in children.

Related collections

Most cited references 39

Record: found
Abstract: found
Article: not found

Minimal Change Disease.

Marina Vivarelli, Laura Massella, Barbara Ruggiero … (2017)

Minimal change disease (MCD) is a major cause of idiopathic nephrotic syndrome (NS), characterized by intense proteinuria leading to edema and intravascular volume depletion. In adults, it accounts for approximately 15% of patients with idiopathic NS, reaching a much higher percentage at younger ages, up to 70%-90% in children >1 year of age. In the pediatric setting, a renal biopsy is usually not performed if presentation is typical and the patient responds to therapy with oral prednisone at conventional doses. Therefore, in this setting steroid-sensitive NS can be considered synonymous with MCD. The pathologic hallmark of disease is absence of visible alterations by light microscopy and effacement of foot processes by electron microscopy. Although the cause is unknown and it is likely that different subgroups of disease recognize a different pathogenesis, immunologic dysregulation and modifications of the podocyte are thought to synergize in altering the integrity of the glomerular basement membrane and therefore determining proteinuria. The mainstay of therapy is prednisone, but steroid-sensitive forms frequently relapse and this leads to a percentage of patients requiring second-line steroid-sparing immunosuppression. The outcome is variable, but forms of MCD that respond to steroids usually do not lead to chronic renal damage, whereas forms that are unresponsive to steroids may subsequently reveal themselves as FSGS. However, in a substantial number of patients the disease is recurrent and requires long-term immunosuppression, with significant morbidity because of side effects. Recent therapeutic advances, such as the use of anti-CD20 antibodies, have provided long-term remission off-therapy and suggest new hypotheses for disease pathogenesis.

0 comments Cited 174 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Idiopathic nephrotic syndrome in children

Kazumoto Iijima, Damien G. Noone, Rulan Parekh (2018)

The incidence of idiopathic nephrotic syndrome (NS) is 1·15-16·9 per 100 000 children, varying by ethnicity and region. The cause remains unknown but the pathogenesis of idiopathic NS is thought to involve immune dysregulation, systemic circulating factors, or inherited structural abnormalities of the podocyte. Genetic risk is more commonly described among children with steroid-resistant disease. The mainstay of therapy is prednisone for the vast majority of patients who are steroid responsive; however, the disease can run a frequently relapsing course, necessitating the need for alternative immunosuppressive agents. Infection and venous thromboembolism are the main complications of NS with also increased risk of acute kidney injury. Prognosis in terms of long-term kidney outcome overall is excellent for steroid-responsive disease, and steroid resistance is an important determinant of future risk of chronic or end-stage kidney disease.

0 comments Cited 168 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: not found
Article: not found

Podocyte biology and response to injury.

Stuart Shankland, Peter Mundel (2002)

0 comments Cited 164 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

Journal ID (nlm-ta): Ann Transl Med

Journal ID (iso-abbrev): Ann Transl Med

Journal ID (publisher-id): ATM

Title: Annals of Translational Medicine

Publisher: AME Publishing Company

ISSN (Print): 2305-5839

ISSN (Electronic): 2305-5847

Publication date (Print and electronic): September 2021

Publication date (Print): September 2021

Volume: 9

Issue: 18

Electronic Location Identifier: 1452

Affiliations

[1 ]Department of Clinical Laboratory, The Children’s Hospital of Zhejiang University School of Medicine , deptNational Clinical Research Center for Child Health , Hangzhou, China;

[2 ]Department of Nephrology, The Children’s Hospital of Zhejiang University School of Medicine , deptNational Clinical Research Center for Child Health , Hangzhou, China;

[3 ]deptDepartment of Pediatric Nephrology , The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University , Wenzhou, China;

[4 ]Department of Nephrology, Children’s Hospital of Fudan University , deptNational Pediatric Medical Center of China , Shanghai, China;

[5 ]Department of Pathology, The Children’s Hospital of Zhejiang University School of Medicine , deptNational Clinical Research Center for Child Health , Hangzhou, China;

[6 ]deptDepartment of Nephrology , Children’s Hospital of Nanjing Medical University , Nanjing, China;

[7 ]deptDepartment of Pediatrics , First Affiliated Hospital of Zhengzhou University , Zhengzhou, China;

[8 ]deptDepartment of Pediatric Nephrology , The First Affiliated Hospital of Guangxi Medical University , Nanning, China;

[9 ]Department of Thoracic and Cardiovascular Surgery, The Children’s Hospital of Zhejiang University School of Medicine , deptNational Clinical Research Center for Child Health , Hangzhou, China

Author notes

Contributions: (I) Conception and design: J Mao, Q Shu; (II) Administrative support: J Mao, Q Shu; (III) Provision of study materials or patients: Q Ye; (IV) Collection and assembly of data: Q Ye, Y Zhang, J Zhuang, Y Bi, H Xu, Q Shen, J Liu, H Fu, J Wang, C Feng, X Tang, F Liu, W Gu, F Zhao, J Zhang, Y Qin, H Shen, A Liu, Y Xia, Z Lu; (V) Data analysis and interpretation: Q Ye, Y Zhang; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.

[#]

These authors contributed equally to this work.

Correspondence to: Jianhua Mao. Department of Nephrology, the Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou 310052, China. Email: maojh88@ 123456zju.edu.cn ; Qiang Shu. Department of Thoracic and Cardiovascular Surgery, the Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou 310052, China. Email: shuqiang@ 123456zju.edu.cn .

Article

Publisher ID: atm-09-18-1452

DOI: 10.21037/atm-21-3988

PMC ID: 8506724

PubMed ID: 34734004

SO-VID: bbfefdc5-fdcc-4f82-89e4-068bc626af30

License:

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0.

History

Date received : 23 July 2021

Date accepted : 01 September 2021

Comments

Comment on this article

scite_

Cited by 16

See all cited by

Most referenced authors 493

See all reference authors

- Version 1