{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T18:26:52Z","timestamp":1793039212461,"version":"4.5.0"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T00:00:00Z","timestamp":1772409600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["NEPHROPROTECTION #394046635, subproject A03, as part of CRC 1365, EXPAND-PD #CA2816\/1, DFG Research Unit FOR5930"],"award-info":[{"award-number":["NEPHROPROTECTION #394046635, subproject A03, as part of CRC 1365, EXPAND-PD #CA2816\/1, DFG Research Unit FOR5930"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Forschung, Technologie und Raumfahrt","doi-asserted-by":"publisher","award":["IMMME2 01EJ2504A"],"award-info":[{"award-number":["IMMME2 01EJ2504A"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Antibody-mediated rejection (AMR) is a leading cause of kidney allograft loss. Anti-angiotensin II type-1 receptor (AT1R) autoantibodies (AABs) have been implicated in AMR and microvascular inflammation (MVI), particularly in C4d-negative and non-HLA antibody dependent cases. Conventional assays measure only total IgG and do not assess pathogenic subclass heterogeneity. Whether IgG1-IgG4 subclass profiling improves AMR prediction has not yet been investigated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We included 143 adult kidney-transplant recipients who underwent indication biopsy between 2018 and 2025. Histopathology was classified according to Banff 2017\u20132022 criteria. Serum samples were analysed for total AT1R-IgG (U\/mL) and AT1R IgG1\u2013IgG4 subclasses (relative optical density). Associations with AMR were assessed using group comparisons, correlation analysis, logistic regression, ROC AUC, and quartile-based analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>AT1R-IgG3 levels were significantly elevated in AMR (Kruskal\u2013Wallis, p = 0.0396), correlated with AMR (Spearman \u03c1 = 0.19, p = 0.02), and demonstrated better predictive performance (AUC 0.63 vs 0.53) than total AT1R-IgG. Logistic regression showed stronger associations for IgG3 (OR 1.33, p = 0.0004) than total AT1R-IgG (OR 1.19, p = 0.029). AMR prevalence increased across IgG3 quartiles (Q1:10.5% \u2192 Q4:31.6%), while no such trend was observed for total AT1R-IgG.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>AT1R antibodies of IgG3 subclass outperform total AT1R levels in predicting AMR, revealing pathogenic antibody patterns that are not detectable through global IgG quantitation. Subclass profiling may contribute to more precise AMR risk assessment, but longitudinal and multicentre validation studies with standardized subclass-specific assays are needed to confirm these findings. Although AT1R IgG3 levels were significantly correlated with AMR, the magnitude of these associations is insufficient to support their use as an independent diagnostic marker and may only serve as a complementary AMR marker.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1776113","type":"journal-article","created":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T05:21:11Z","timestamp":1772428871000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Anti-angiotensin II type 1 receptor autoantibodies of IgG3 subclass outperform total anti-AT1R IgG1-IgG4 levels in predicting transplanted kidney antibody-mediated rejection"],"prefix":"10.3389","volume":"17","author":[{"given":"Jakub","family":"Mizera","sequence":"first","affiliation":[{"name":"Department of Nephrology, Transplantation Medicine and Internal Diseases, Institute of Internal Diseases, Wroclaw Medical University","place":["Wroclaw, Poland"]},{"name":"University Clinical Hospital in Wroclaw","place":["Wroclaw, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karolina","family":"Marek-Bukowiec","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Transplantation Medicine and Internal Diseases, Institute of Internal Diseases, Wroclaw Medical University","place":["Wroclaw, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guido","family":"Moll","sequence":"additional","affiliation":[{"name":"Berlin Institute of Health (BIH) Center and School for Regenerative Therapies (BCRT\/BSRT), Charit\u00e9 Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health (BIH)","place":["Berlin, Germany"]},{"name":"Julius Wolff Institute (JWI), Charit\u00e9 Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health (BIH)","place":["Berlin, Germany"]},{"name":"Department of Nephrology and Internal Intensive Care Medicine, Charit\u00e9 Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health (BIH)","place":["Berlin, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rusan","family":"Catar","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Internal Intensive Care Medicine, Charit\u00e9 Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health (BIH)","place":["Berlin, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harald","family":"Heidecke","sequence":"additional","affiliation":[{"name":"CellTrend GmbH","place":["Luckenwalde, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Schulze-Forster","sequence":"additional","affiliation":[{"name":"CellTrend GmbH","place":["Luckenwalde, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patryk","family":"Jerzak","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Transplantation Medicine and Internal Diseases, Institute of Internal Diseases, Wroclaw Medical University","place":["Wroclaw, Poland"]},{"name":"University Clinical Hospital in Wroclaw","place":["Wroclaw, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mateusz","family":"Rakowski","sequence":"additional","affiliation":[{"name":"University Clinical Hospital in Wroclaw","place":["Wroclaw, Poland"]},{"name":"Faculty of Health Sciences, Wroclaw Medical University","place":["Wroclaw, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karolina","family":"W\u0142adyczak","sequence":"additional","affiliation":[{"name":"University Clinical Hospital in Wroclaw","place":["Wroclaw, Poland"]},{"name":"Department of Clinical and Experimental Pathology, Wroclaw Medical University","place":["Wroclaw, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnieszka","family":"Ha\u0142o\u0144","sequence":"additional","affiliation":[{"name":"University Clinical Hospital in Wroclaw","place":["Wroclaw, Poland"]},{"name":"Department of Clinical and Experimental Pathology, Wroclaw Medical University","place":["Wroclaw, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dariusz","family":"Janczak","sequence":"additional","affiliation":[{"name":"University Clinical Hospital in Wroclaw","place":["Wroclaw, Poland"]},{"name":"Department of Vascular, General, and Transplant Surgery, Wroclaw Medical University","place":["Wroclaw, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piotr","family":"Donizy","sequence":"additional","affiliation":[{"name":"University Clinical Hospital in Wroclaw","place":["Wroclaw, Poland"]},{"name":"Department of Clinical and Experimental Pathology, Wroclaw Medical University","place":["Wroclaw, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miros\u0142aw","family":"Banasik","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Transplantation Medicine and Internal Diseases, Institute of Internal Diseases, Wroclaw Medical University","place":["Wroclaw, Poland"]},{"name":"University Clinical Hospital in Wroclaw","place":["Wroclaw, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1111\/J.1600-6143.2011.03840.X","article-title":"Understanding the causes of kidney transplant failure: the dominant role of antibody-mediated rejection and nonadherence","volume":"12","author":"Sellar\u00e9s","year":"2012","journal-title":"Am J Transplant"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMRA1802677","article-title":"Antibody-mediated rejection of solid-organ allografts","volume":"379","author":"Loupy","year":"2018","journal-title":"N Engl J Med"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/J.AJT.2023.10.016","article-title":"The banff 2022 kidney meeting report: reappraisal of microvascular inflammation and the role of biopsy-based transcript diagnostics","volume":"24","author":"Naesens","year":"2024","journal-title":"Am J Transplant"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3389\/FIMMU.2025.1659939","article-title":"Angiotensin II type 1 receptor antibodies as a contributor to microvascular inflammation in kidney transplant recipients: insights from statistical and artificial intelligence based approaches","volume":"16","author":"Mizera","year":"2025","journal-title":"Front Immunol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3389\/FIMMU.2024.1393026","article-title":"Editorial: emerging talents in alloimmunity and transplantation: 2022","volume":"15","author":"Moll","year":"2024","journal-title":"Front Immunol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3389\/FIMMU.2024.1516554","article-title":"Editorial: methods in alloimmunity and transplantation: 2023","volume":"15","author":"Moll","year":"2024","journal-title":"Front Immunol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/678180","article-title":"The importance of C4d in biopsies of kidney transplant recipients","volume":"2013","author":"Corr\u00eaa","year":"2013","journal-title":"Clin Dev Immunol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2009101065","article-title":"Preexisting donor-specific HLA antibodies predict outcome in kidney transplantation","volume":"21","author":"Lefaucheur","year":"2010","journal-title":"J Am Soc Nephrol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.13661","article-title":"The revised (2013) banff classification for antibody-mediated rejection of renal allografts: update, difficulties, and future considerations","volume":"16","author":"Haas","year":"2016","journal-title":"Am J Transplant"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMOA2408835","article-title":"Microvascular inflammation of kidney allografts and clinical outcomes","volume":"392","author":"Sablik","year":"2025","journal-title":"N Engl J Med"},{"key":"B11","doi-asserted-by":"publisher","first-page":"103855","DOI":"10.1016\/j.autrev.2025.103855","article-title":"Advancing research on regulatory autoantibodies targeting GPCRs: insights from the 5th international symposium","volume":"24","author":"Cabral-Marques","year":"2025","journal-title":"Autoimmun Rev"},{"key":"B12","doi-asserted-by":"publisher","first-page":"103310","DOI":"10.1016\/j.autrev.2023.103310","article-title":"Autoantibodies targeting G protein-coupled receptors: an evolving history in autoimmunity. Report of the 4th international symposium","volume":"22","author":"Cabral-Marques","year":"2023","journal-title":"Autoimmun Rev"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMOA035717","article-title":"Angiotensin II type 1-receptor activating antibodies in renal-allograft rejection","volume":"352","author":"Dragun","year":"2005","journal-title":"N Engl J Med"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.ekir.2020.09.004","article-title":"Endothelin type A receptor antibodies are associated with angiotensin II type 1 receptor antibodies, vascular inflammation, and decline in renal function in pediatric kidney transplantation","volume":"5","author":"Pearl","year":"2020","journal-title":"Kidney Int Rep"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1136\/ANNRHEUMDIS-2021-222088","article-title":"Induced antibodies directed to the angiotensin receptor type 1 provoke skin and lung inflammation, dermal fibrosis and act species overarching","volume":"81","author":"Yue","year":"2022","journal-title":"Ann Rheum Dis"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.3389\/FIMMU.2014.00520","article-title":"IgG subclasses and allotypes: from structure to effector functions","volume":"5","author":"Vidarsson","year":"2014","journal-title":"Front Immunol"},{"key":"B17","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1681\/ASN.2014111120","article-title":"IgG donor-specific anti-human HLA antibody subclasses and kidney allograft antibody-mediated injury","volume":"27","author":"Lefaucheur","year":"2016","journal-title":"J Am Soc Nephrol"},{"key":"B18","doi-asserted-by":"publisher","first-page":"2318","DOI":"10.1111\/AJT.15898","article-title":"The banff 2019 kidney meeting report (I): updates on and clarification of criteria for T cell\u2013 and antibody-mediated rejection","volume":"20","author":"Loupy","year":"2020","journal-title":"Am J Transplant"},{"key":"B19","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1111\/AJT.14625","article-title":"The banff 2017 kidney meeting report: revised diagnostic criteria for chronic active T cell\u2013mediated rejection, antibody-mediated rejection, and prospects for integrative endpoints for next-generation clinical trials","volume":"18","author":"Haas","year":"2018","journal-title":"Am J Transplant"},{"key":"B20","article-title":"pandas-dev\/pandas: Pandas (v2.3.0)","volume-title":"Zenodo","year":"2025"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2649-2","article-title":"Array programming with numPy","volume":"585","author":"Harris","year":"2020","journal-title":"Nature"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1038\/S41592-019-0686-2;SUBJMETA=114,45,559,56,631,703,706;KWRD=BIOPHYSICAL+CHEMISTRY,COMPUTATIONAL+BIOLOGY+AND+BIOINFORMATICS,TECHNOLOGY","article-title":"SciPy 1.0: fundamental algorithms for scientific computing in python","volume":"17","author":"Virtanen","year":"2020","journal-title":"Nat Methods"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.25080\/MAJORA-92BF1922-011","article-title":"Statsmodels: econometric and statistical modeling with python","author":"Seabold","year":"2010","journal-title":"scipy"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.5555\/1953048.2078195","article-title":"Scikit-learn: machine learning in python","volume":"12","author":"Pedregosa","year":"2011","journal-title":"J Mach Learn Res"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.21105\/JOSS.03021","article-title":"Seaborn: statistical data visualization","volume":"6","author":"Waskom","year":"2021","journal-title":"J Open Source Softw"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1109\/MCSE.2007.55","article-title":"Matplotlib: A 2D graphics environment","volume":"9","author":"Hunter","year":"2007","journal-title":"Comput Sci Eng"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.17219\/ACEM\/121510","article-title":"The significance of angiotensin II type 1 receptor (AT1 receptor) in renal transplant injury","volume":"29","author":"Sas-Str\u00f3zik","year":"2020","journal-title":"Adv Clin Exp Med"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.transproceed.2007.08.064","article-title":"C4D deposition and positive posttransplant crossmatch are not necessarily markers of antibody-mediated rejection in renal allograft recipients","volume":"39","author":"Banasik","year":"2007","journal-title":"Transplant Proc"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0B013E3181FD97F1","article-title":"Anti-angiotensin type 1 receptor antibodies associated with antibody mediated rejection in donor HLA antibody negative patients","volume":"90","author":"Reinsmoen","year":"2010","journal-title":"Transplantation"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.12397","article-title":"Pretransplant sensitization against angiotensin II type 1 receptor is a risk factor for acute rejection and graft loss","volume":"13","author":"Giral","year":"2013","journal-title":"Am J Transplant"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.12395","article-title":"Higher risk of kidney graft failure in the presence of anti-angiotensin II type-1 receptor antibodies","volume":"13","author":"Taniguchi","year":"2013","journal-title":"Am J Transplant"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1111\/TRI.13009","article-title":"Is pre-transplant sensitization against angiotensin II type 1 receptor still a risk factor of graft and patient outcome in kidney transplantation in the anti-HLA luminex era? A retrospective study","volume":"30","author":"Deltombe","year":"2017","journal-title":"Transpl Int"},{"key":"B33","doi-asserted-by":"publisher","first-page":"692","DOI":"10.1681\/ASN.2018080868","article-title":"Early acute microvascular kidney transplant rejection in the absence of anti-HLA antibodies is associated with preformed igG antibodies against diverse glomerular endothelial cell antigens","volume":"30","author":"Delville","year":"2019","journal-title":"J Am Soc Nephrol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1093\/icvts\/ivv344","article-title":"The impact of angiotensin II type 1 receptor antibodies on post-heart transplantation outcome in heart mate II bridged recipients","volume":"22","author":"Urban","year":"2016","journal-title":"Interactive Cardiovasc Thorac Surg"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.4049\/JIMMUNOL.2300307","article-title":"The influence of human igG subclass and allotype on complement activation","volume":"211","author":"Damelang","year":"2023","journal-title":"J Immunol"},{"key":"B36","doi-asserted-by":"publisher","first-page":"975","DOI":"10.3390\/JCM14030975","article-title":"Advancements in artificial intelligence for kidney transplantology: A comprehensive review of current applications and predictive models","volume":"14","author":"Mizera","year":"2025","journal-title":"J Clin Med"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1093\/stmcls\/sxae054","article-title":"The global evolution and impact of systems biology and artificial intelligence in stem cell research and therapeutics development: a scoping review","volume":"42","author":"Silva-Sousa","year":"2024","journal-title":"Stem Cells"},{"key":"B38","doi-asserted-by":"publisher","first-page":"szaf037","DOI":"10.1093\/stcltm\/szaf037","article-title":"Artificial intelligence and systems biology analysis in stem cell research and therapeutics development","volume":"14","author":"Silva-Sousa","year":"2025","journal-title":"Stem Cells Trans Med"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1776113\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T05:21:12Z","timestamp":1772428872000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1776113\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,2]]},"references-count":38,"alternative-id":["10.3389\/fimmu.2026.1776113"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1776113","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,2]]},"article-number":"1776113"}}