The important roles and molecular mechanisms of annexin A2 autoantibody in children with nephrotic syndrome
2021 Annals of Translational Medicine. All rights reserved..
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 A2 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 A2 antibody could induce proteinuria in vivo. Mechanistically, the effect of Annexin A2 antibody on the Rho signaling pathway was realized through promoting the phosphorylation of Annexin A2 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 A2 autoantibody may be responsible for some cases of PNS with MCD/FSGS in children.
| Errataetall: |
ErratumIn: Ann Transl Med. 2023 Oct 25;11(11):401. - PMID 37970603 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:9 |
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| Enthalten in: |
Annals of translational medicine - 9(2021), 18 vom: 29. Sept., Seite 1452 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Ye, Qing [VerfasserIn] |
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| Links: |
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| Themen: |
Chronic kidney disease |
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| Anmerkungen: |
Date Revised 16.11.2023 published: Print ErratumIn: Ann Transl Med. 2023 Oct 25;11(11):401. - PMID 37970603 Citation Status PubMed-not-MEDLINE |
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| doi: |
10.21037/atm-21-3988 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 4 | |a The important roles and molecular mechanisms of annexin A2 autoantibody in children with nephrotic syndrome |
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| 500 | |a Date Revised 16.11.2023 | ||
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| 500 | |a ErratumIn: Ann Transl Med. 2023 Oct 25;11(11):401. - PMID 37970603 | ||
| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a 2021 Annals of Translational Medicine. All rights reserved. | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a RESULTS: Annexin A2 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 A2 antibody could induce proteinuria in vivo. Mechanistically, the effect of Annexin A2 antibody on the Rho signaling pathway was realized through promoting the phosphorylation of Annexin A2 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 | ||
| 520 | |a CONCLUSIONS: Annexin A2 autoantibody may be responsible for some cases of PNS with MCD/FSGS in children | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Chronic kidney disease | |
| 650 | 4 | |a cytoskeleton | |
| 650 | 4 | |a nephrotic syndrome | |
| 650 | 4 | |a pediatric nephrology | |
| 650 | 4 | |a podocyte | |
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| 700 | 1 | |a Fu, Haidong |e verfasserin |4 aut | |
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