{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:17:47Z","timestamp":1787030267320,"version":"build-2736575974"},"reference-count":31,"publisher":"American Association for the Advancement of Science (AAAS)","funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82270741"],"award-info":[{"award-number":["82270741"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017623","name":"Zhejiang Provincial Outstanding Youth Science Foundation","doi-asserted-by":"publisher","award":["LR24H200001"],"award-info":[{"award-number":["LR24H200001"]}],"id":[{"id":"10.13039\/501100017623","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Central Government Guides Local Science and Technology Development Funds","award":["2024ZY01007"],"award-info":[{"award-number":["2024ZY01007"]}]},{"DOI":"10.13039\/501100012279","name":"Zhejiang Xinmiao Talents Program","doi-asserted-by":"publisher","award":["2023R401208"],"award-info":[{"award-number":["2023R401208"]}],"id":[{"id":"10.13039\/501100012279","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Children's Hospital of Zhejiang University School of Medicine Pre Research Fund","award":["CHZJU2024YY005"],"award-info":[{"award-number":["CHZJU2024YY005"]}]}],"content-domain":{"domain":["spj.science.org"],"crossmark-restriction":true},"short-container-title":["Research"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:p>\n                    <jats:bold>Background:<\/jats:bold>\n                    Emerging evidence suggests that autoantibodies targeting podocytes are potential contributors to idiopathic nephrotic syndrome (INS); however, the specific mechanisms remain unclear. This study aims to explore the pathogenic role and underlying mechanisms of anti-vinculin autoantibodies in INS.\n                    <jats:bold>Methods:<\/jats:bold>\n                    Serum anti-vinculin autoantibody levels detected by protein microarray and clinical data were compared among INS patients (\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    = 147), healthy individuals (\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    = 84), and patients with other kidney or immune diseases (\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    = 100 of each disease). Immune-mediated mouse models were established to verify the pathogenicity of anti-vinculin autoantibodies. Mouse urine was monitored for urine protein levels, while immunofluorescence, pathological staining, and electron microscopy assessed kidney pathological and ultrastructural changes. Transcriptome sequencing of mouse kidney tissues was performed to investigate the key molecular mechanisms and signaling pathways involved in kidney injury post-immunization.\n                    <jats:bold>Results:<\/jats:bold>\n                    Anti-vinculin autoantibody levels were specifically elevated in INS patients, with a 54.42% positivity rate, correlating with urinary albumin, serum albumin, cholesterol, and CD19 levels. The average anti-vinculin autoantibody levels dropped markedly in pediatric INS patients during remission. Mouse experiments revealed that injecting anti-vinculin antibodies or recombinant vinculin protein induced proteinuria and podocyte injury in the immunized mice, and the renal phenotype closely resembled the pathological characteristics of minimal change disease. Transcriptome sequencing of renal tissues revealed up-regulation of inflammation, immune responses, cytokine activities, and B cell activation pathways in the immunized mice, while cytoskeleton-related functions were down-regulated.\n                    <jats:bold>Conclusions:<\/jats:bold>\n                    Autoantibodies targeting vinculin act as pathogenic autoantibodies in INS and hold potential value for diagnosing and monitoring INS progression.\n                  <\/jats:p>","DOI":"10.34133\/research.0722","type":"journal-article","created":{"date-parts":[[2025,5,12]],"date-time":"2025-05-12T16:28:33Z","timestamp":1747067313000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark_01","source":"Crossref","is-referenced-by-count":5,"title":["Autoantibodies Targeting Vinculin Reveal Novel Insight into the Mechanisms of Autoimmune Podocytopathies"],"prefix":"10.34133","volume":"8","author":[{"given":"Hanyan","family":"Meng","sequence":"first","affiliation":[{"name":"Department of Nephrology, Children\u2019s Hospital, \rZhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children\u2019s Regional Medical Center, Hangzhou 310052, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongjie","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Children\u2019s Hospital, \rZhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children\u2019s Regional Medical Center, Hangzhou 310052, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Children\u2019s Hospital, \rZhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children\u2019s Regional Medical Center, Hangzhou 310052, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Children\u2019s Hospital, \rZhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children\u2019s Regional Medical Center, Hangzhou 310052, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinrui","family":"Mao","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Children\u2019s Hospital, \rZhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children\u2019s Regional Medical Center, Hangzhou 310052, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinglan","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Children\u2019s Hospital, \rZhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children\u2019s Regional Medical Center, Hangzhou 310052, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohui","family":"Qiao","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Women and Children\u2019s Hospital of Ningbo University","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Children\u2019s Hospital, \rZhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children\u2019s Regional Medical Center, Hangzhou 310052, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjing","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Children\u2019s Hospital, \rZhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children\u2019s Regional Medical Center, Hangzhou 310052, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haidong","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Children\u2019s Hospital, \rZhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children\u2019s Regional Medical Center, Hangzhou 310052, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianhua","family":"Mao","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Children\u2019s Hospital, \rZhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children\u2019s Regional Medical Center, Hangzhou 310052, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6756-0630","authenticated-orcid":true,"given":"Qing","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Children\u2019s Hospital, \rZhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children\u2019s Regional Medical Center, Hangzhou 310052, China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","published-online":{"date-parts":[[2025,6,3]]},"reference":[{"issue":"2","key":"e_1_3_4_2_2","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.kint.2024.10.027","article-title":"The autoimmune architecture of childhood idiopathic nephrotic syndrome","volume":"107","author":"Al-Aubodah TA","year":"2024","unstructured":"Al-Aubodah TA, Piccirillo CA, Trachtman H, Takano T. The autoimmune architecture of childhood idiopathic nephrotic syndrome. Kidney Int. 2024;107(2):271\u2013279.","journal-title":"Kidney Int"},{"issue":"5","key":"e_1_3_4_3_2","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1056\/NEJMoa2314471","article-title":"Autoantibodies targeting nephrin in podocytopathies","volume":"391","author":"Hengel FE","year":"2024","unstructured":"Hengel FE, Dehde S, Lass\u00e9 M, Zahner G, Seifert L, Schnarre A, Kretz O, Demir F, Pinnschmidt HO, Grahammer F, et al. Autoantibodies targeting nephrin in podocytopathies. N Engl J Med. 2024;391(5):422\u2013433.","journal-title":"N Engl J Med"},{"issue":"1","key":"e_1_3_4_4_2","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1053\/j.akdh.2024.10.004","article-title":"Podocytopathies","volume":"32","author":"Navarro-Torres M","year":"2025","unstructured":"Navarro-Torres M, Wooden B, Santoriello D, Radhakrishnan J, Bomback AS. Podocytopathies. Adv Kidney Dis Health. 2025;32(1):2\u201311.","journal-title":"Adv Kidney Dis Health"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25115613"},{"issue":"2","key":"e_1_3_4_6_2","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1080\/01913123.2023.2292590","article-title":"Punctate IgG staining particles localize in the budding ballooning clusters of reactive foot processes in minimal change disease","volume":"48","author":"Zhang PL","year":"2023","unstructured":"Zhang PL, Mahalingam VD, Metcalf BD, Al-Othman YA, Li W, Kanaan HD, Herrera GA. Punctate IgG staining particles localize in the budding ballooning clusters of reactive foot processes in minimal change disease. Ultrastruct Pathol. 2023;48(2):121\u2013127.","journal-title":"Ultrastruct Pathol"},{"issue":"6","key":"e_1_3_4_7_2","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1016\/j.kint.2024.09.006","article-title":"Anti-slit diaphragm antibodies on kidney biopsy identify pediatric patients with steroid-resistant nephrotic syndrome responsive to second-line immunosuppressants","volume":"106","author":"Raglianti V","year":"2024","unstructured":"Raglianti V, Angelotti ML, Cirillo L, Ravaglia F, Landini S, Palazzo V, Melica ME, Antonelli G, Conte C, Buti E, et al. Anti-slit diaphragm antibodies on kidney biopsy identify pediatric patients with steroid-resistant nephrotic syndrome responsive to second-line immunosuppressants. Kidney Int. 2024;106(6):1124\u20131134.","journal-title":"Kidney Int"},{"issue":"1","key":"e_1_3_4_8_2","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1681\/ASN.2021060794","article-title":"Discovery of autoantibodies targeting nephrin in minimal change disease supports a novel autoimmune etiology","volume":"33","author":"Watts AJB","year":"2022","unstructured":"Watts AJB, Keller KH, Lerner G, Rosales I, Collins AB, Sekulic M, Waikar SS, Chandraker A, Riella LV, Alexander MP, et al. Discovery of autoantibodies targeting nephrin in minimal change disease supports a novel autoimmune etiology. J Am Soc Nephrol. 2022;33(1):238\u2013252.","journal-title":"J Am Soc Nephrol."},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2017.12.014"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2022010070"},{"issue":"11","key":"e_1_3_4_11_2","doi-asserted-by":"crossref","first-page":"3332","DOI":"10.1016\/j.ekir.2024.08.021","article-title":"Efficacy and safety of subcutaneous rituximab in idiopathic nephrotic syndrome","volume":"9","author":"Cravedi P","year":"2024","unstructured":"Cravedi P, Bigatti C, Kajana X, Verrina EE, Caridi G, Bruschi M, Ghiggeri GM, Angeletti A. Efficacy and safety of subcutaneous rituximab in idiopathic nephrotic syndrome. Kidney Int Rep. 2024;9(11):3332\u20133334.","journal-title":"Kidney Int Rep"},{"key":"e_1_3_4_12_2","doi-asserted-by":"crossref","first-page":"205435811769866","DOI":"10.1177\/2054358117698667","article-title":"Rituximab in minimal change disease: Mechanisms of action and hypotheses for future studies","volume":"4","author":"Madanchi N","year":"2017","unstructured":"Madanchi N, Bitzan M, Takano T. Rituximab in minimal change disease: Mechanisms of action and hypotheses for future studies. Can J Kidney Health Dis. 2017;4:2054358117698667.","journal-title":"Can J Kidney Health Dis"},{"issue":"3","key":"e_1_3_4_13_2","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1016\/j.kint.2023.11.022","article-title":"A multi-institutional study found a possible role of anti-nephrin antibodies in post-transplant focal segmental glomerulosclerosis recurrence","volume":"105","author":"Shirai Y","year":"2023","unstructured":"Shirai Y, Miura K, Ishizuka K, Ando T, Kanda S, Hashimoto J, Hamasaki Y, Hotta K, Ito N, Honda K, et al. A multi-institutional study found a possible role of anti-nephrin antibodies in post-transplant focal segmental glomerulosclerosis recurrence. Kidney Int. 2023;105(3):608\u2013617.","journal-title":"Kidney Int"},{"issue":"4","key":"e_1_3_4_14_2","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1681\/ASN.0000000642","article-title":"Anti-slit antibodies against Podocin and Kirrel1 in pediatric and adult podocytopathies","volume":"36","author":"Raglianti V","year":"2025","unstructured":"Raglianti V, Angelotti ML, De Chiara L, Allinovi M, Cirillo L, Manonelles A, Cruzado JM, Melica ME, Antonelli G, Conte C, et al. Anti-slit antibodies against Podocin and Kirrel1 in pediatric and adult podocytopathies. J Am Soc Nephrol. 2025;36(4):702\u2013705.","journal-title":"J Am Soc Nephrol"},{"issue":"2","key":"e_1_3_4_15_2","doi-asserted-by":"crossref","DOI":"10.1002\/ctm2.1177","article-title":"Comprehensive mapping of B lymphocyte immune dysfunction in idiopathic nephrotic syndrome children","volume":"13","author":"Ye Q","year":"2023","unstructured":"Ye Q, Liu H, Wang D, Mao J. Comprehensive mapping of B lymphocyte immune dysfunction in idiopathic nephrotic syndrome children. Clin Transl Med. 2023;13(2): Article e1177.","journal-title":"Clin Transl Med"},{"issue":"3","key":"e_1_3_4_16_2","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1007\/s12519-022-00640-3","article-title":"T-cell and B-cell repertoire diversity are selectively skewed in children with idiopathic nephrotic syndrome revealed by high-throughput sequencing","volume":"19","author":"Ye Q","year":"2023","unstructured":"Ye Q, Wang DJ, Lan B, Mao JH. T-cell and B-cell repertoire diversity are selectively skewed in children with idiopathic nephrotic syndrome revealed by high-throughput sequencing. World J Pediatr. 2023;19(3):273\u2013282.","journal-title":"World J Pediatr"},{"issue":"18","key":"e_1_3_4_17_2","doi-asserted-by":"crossref","first-page":"1452","DOI":"10.21037\/atm-21-3988","article-title":"The important roles and molecular mechanisms of annexin A2 autoantibody in children with nephrotic syndrome","volume":"9","author":"Ye Q","year":"2021","unstructured":"Ye Q, Zhang Y, Zhuang J, Bi Y, Xu H, Shen Q, Liu J, Fu H, Wang J, Feng C, et al. The important roles and molecular mechanisms of annexin A2 autoantibody in children with nephrotic syndrome. Ann Transl Med. 2021;9(18):1452.","journal-title":"Ann Transl Med"},{"key":"e_1_3_4_18_2","doi-asserted-by":"crossref","first-page":"108869","DOI":"10.1016\/j.clim.2021.108869","article-title":"Seven novel podocyte autoantibodies were identified to diagnosis a new disease subgroup-autoimmune podocytopathies","volume":"232","author":"Ye Q","year":"2021","unstructured":"Ye Q, Zhou C, Wang D, Fu H, Wang J, Mao J. Seven novel podocyte autoantibodies were identified to diagnosis a new disease subgroup-autoimmune podocytopathies. Clin Immunol. 2021;232:108869.","journal-title":"Clin Immunol"},{"issue":"3","key":"e_1_3_4_19_2","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1681\/ASN.0000000525","article-title":"Autoantibodies targeting proteasome subunit alpha type 1 in autoimmune podocytopathies","volume":"36","author":"Liu H","year":"2024","unstructured":"Liu H, Zhou C, Wang D, Meng H, Zhu S, Zhang J, Mao J, Ye Q. Autoantibodies targeting proteasome subunit alpha type 1 in autoimmune podocytopathies. J Am Soc Nephrol. 2024;36(3):406\u2013419.","journal-title":"J Am Soc Nephrol"},{"issue":"3","key":"e_1_3_4_20_2","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1681\/ASN.2021111469","article-title":"Autoimmune podocytopathies: A novel sub-group of diseases from childhood idiopathic nephrotic syndrome","volume":"33","author":"Ye Q","year":"2022","unstructured":"Ye Q, Chen A, Lai EY, Mao J. Autoimmune podocytopathies: A novel sub-group of diseases from childhood idiopathic nephrotic syndrome. J Am Soc Nephrol. 2022;33(3):653\u2013654.","journal-title":"J Am Soc Nephrol"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.34133\/research.0270"},{"issue":"1","key":"e_1_3_4_22_2","doi-asserted-by":"crossref","first-page":"9497","DOI":"10.1038\/s41467-024-53859-1","article-title":"Talin and vinculin combine their activities to trigger actin assembly","volume":"15","author":"Wang H","year":"2024","unstructured":"Wang H, Said R, Nguyen-Vigouroux C, Henriot V, Gebhardt P, Pernier J, Grosse R, Le Clainche C. Talin and vinculin combine their activities to trigger actin assembly. Nat Commun. 2024;15(1):9497.","journal-title":"Nat Commun."},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2017.09.021"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.34133\/research.0220"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2024.12.006"},{"issue":"1","key":"e_1_3_4_26_2","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1186\/s12951-024-02633-y","article-title":"Future embracing: Exosomes driving a revolutionary approach to the diagnosis and treatment of idiopathic membranous nephropathy","volume":"22","author":"Wang L","year":"2024","unstructured":"Wang L, Wang J, Xu A, Wei L, Pei M, Shen T, Xian X, Yang K, Fei L, Pan Y, et al. Future embracing: Exosomes driving a revolutionary approach to the diagnosis and treatment of idiopathic membranous nephropathy. J Nanobiotechnology. 2024;22(1):472.","journal-title":"J Nanobiotechnology"},{"issue":"8","key":"e_1_3_4_27_2","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.34067\/KID.0000000000000499","article-title":"Minimal change disease and FSGS are a spectrum of a single disease within immune-mediated nephrotic syndrome","volume":"5","author":"Sim JJ","year":"2024","unstructured":"Sim JJ, Smoyer WE, Schachter AD. Minimal change disease and FSGS are a spectrum of a single disease within immune-mediated nephrotic syndrome. Kidney360. 2024;5(8):1197\u20131199.","journal-title":"Kidney360"},{"issue":"2","key":"e_1_3_4_28_2","article-title":"Nephrotic syndrome: A review","volume":"16","author":"Verma PR","year":"2024","unstructured":"Verma PR, Patil P. Nephrotic syndrome: A review. Cureus. 2024;16(2): Article e53923.","journal-title":"Cureus"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1111\/joim.20024"},{"issue":"1","key":"e_1_3_4_30_2","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1186\/s12955-024-02310-6","article-title":"Assessment of health-related quality of life of children with idiopathic nephrotic syndrome and their caregivers in China","volume":"22","author":"Wang X","year":"2024","unstructured":"Wang X, Tan DJ, Guan L, Shao Y, Wang J, Feng C, Fu H, Shen H, Zhu X, Rafay A, et al. Assessment of health-related quality of life of children with idiopathic nephrotic syndrome and their caregivers in China. Health Qual Life Outcomes. 2024;22(1):94.","journal-title":"Health Qual Life Outcomes"},{"issue":"8","key":"e_1_3_4_31_2","article-title":"Corticosteroid therapy for nephrotic syndrome in children","volume":"8","author":"Hahn D","year":"2024","unstructured":"Hahn D, Samuel SM, Willis NS, Craig JC, Hodson EM. Corticosteroid therapy for nephrotic syndrome in children. Cochrane Database Syst Rev. 2024;8(8): Article Cd001533.","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00467-022-05520-6"}],"container-title":["Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/spj.science.org\/doi\/pdf\/10.34133\/research.0722","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,3]],"date-time":"2025-06-03T10:51:56Z","timestamp":1748947916000},"score":1,"resource":{"primary":{"URL":"https:\/\/spj.science.org\/doi\/10.34133\/research.0722"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1]]},"references-count":31,"alternative-id":["10.34133\/research.0722"],"URL":"https:\/\/doi.org\/10.34133\/research.0722","relation":{},"ISSN":["2639-5274"],"issn-type":[{"value":"2639-5274","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1]]},"assertion":[{"value":"2025-03-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-18","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-05","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-03","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"0722"}}