{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T05:39:15Z","timestamp":1777354755203,"version":"3.51.4"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T00:00:00Z","timestamp":1777334400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100014013","name":"UK Research and Innovation","doi-asserted-by":"publisher","award":["MR\/S025502\/1, MR\/R001359\/1"],"award-info":[{"award-number":["MR\/S025502\/1, MR\/R001359\/1"]}],"id":[{"id":"10.13039\/100014013","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004185","name":"Northern Counties Kidney Research Fund","doi-asserted-by":"publisher","award":["07.04, 06.02"],"award-info":[{"award-number":["07.04, 06.02"]}],"id":[{"id":"10.13039\/501100004185","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"\n Introduction<\/jats:title>\n We have previously shown that the C3D1115N mouse, engineered around a single point mutation in C3 associated with atypical haemolytic uraemic syndrome (aHUS) in man, fully recapitulates the clinical disease. In this study, we investigated the role of properdin in aHUS.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n C3D1115N mice were crossed onto properdin-deficient mice or C3D1115N mice were treated with anti-properdin monoclonal antibody therapy and survival tracked. Kidney function, serum biomarkers and kidney pathology was carefully assessed at set end points. C3 and Fibrin deposition was assessed using immuno-fluorescence.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n We have found that removing properdin ameliorates disease, although two mice had evidence of renal disease over a ~6-month period. Therapeutic treatment with an anti-properdin monoclonal antibody (14E1) after evidence of clinical disease was sufficient to block the progression of disease, suggesting that measures to reduce the stability of the alternative pathway C3 and C5 convertases can help prevent thrombotic microangiopathic anaemia (TMA)\/aHUS.<\/jats:p>\n <\/jats:sec>\n \n Discussion<\/jats:title>\n Our data indicate that a fine balance exists between disease progression and resolution in our C3 gain-of-function model. The data also suggest that anti-properdin therapy, as noted in another mouse model of TMA, may provide a viable treatment option to maintain remission in complement mediated aHUS.<\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1828298","type":"journal-article","created":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T04:48:12Z","timestamp":1777351692000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Properdin deficiency or anti-properdin treatment ameliorates disease in the C3 gain-of-function mouse model of atypical haemolytic uraemic syndrome"],"prefix":"10.3389","volume":"17","author":[{"given":"Grace","family":"Mallett","sequence":"first","affiliation":[{"name":"Complement Therapeutics Research Group, Translational and Clinical Research Institute, Newcastle University","place":["Newcastle-upon-Tyne, United Kingdom"]},{"name":"National Renal Complement Therapeutics Centre, The Royal Victoria Infirmary","place":["Newcastle-upon-Tyne, United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ola","family":"Kamala","sequence":"additional","affiliation":[{"name":"Complement Therapeutics Research Group, Translational and Clinical Research Institute, Newcastle University","place":["Newcastle-upon-Tyne, United Kingdom"]},{"name":"National Renal Complement Therapeutics Centre, The Royal Victoria Infirmary","place":["Newcastle-upon-Tyne, United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabel Y.","family":"Pappworth","sequence":"additional","affiliation":[{"name":"Complement Therapeutics Research Group, Translational and Clinical Research Institute, Newcastle University","place":["Newcastle-upon-Tyne, United Kingdom"]},{"name":"National Renal Complement Therapeutics Centre, The Royal Victoria Infirmary","place":["Newcastle-upon-Tyne, United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kate","family":"Smith-Jackson","sequence":"additional","affiliation":[{"name":"Complement Therapeutics Research Group, Translational and Clinical Research Institute, Newcastle University","place":["Newcastle-upon-Tyne, United Kingdom"]},{"name":"National Renal Complement Therapeutics Centre, The Royal Victoria Infirmary","place":["Newcastle-upon-Tyne, United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beth G.","family":"Gibson","sequence":"additional","affiliation":[{"name":"Complement Therapeutics Research Group, Translational and Clinical Research Institute, Newcastle University","place":["Newcastle-upon-Tyne, United Kingdom"]},{"name":"National Renal Complement Therapeutics Centre, The Royal Victoria Infirmary","place":["Newcastle-upon-Tyne, United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muhammad","family":"Asif","sequence":"additional","affiliation":[{"name":"Complement Therapeutics Research Group, Translational and Clinical Research Institute, Newcastle University","place":["Newcastle-upon-Tyne, United Kingdom"]},{"name":"National Renal Complement Therapeutics Centre, The Royal Victoria Infirmary","place":["Newcastle-upon-Tyne, United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harriet","family":"Denton","sequence":"additional","affiliation":[{"name":"Complement Therapeutics Research Group, Translational and Clinical Research Institute, Newcastle University","place":["Newcastle-upon-Tyne, United Kingdom"]},{"name":"National Renal Complement Therapeutics Centre, The Royal Victoria Infirmary","place":["Newcastle-upon-Tyne, United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charlotte","family":"Cox","sequence":"additional","affiliation":[{"name":"Complement Therapeutics Research Group, Translational and Clinical Research Institute, Newcastle University","place":["Newcastle-upon-Tyne, United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick","family":"Walsh","sequence":"additional","affiliation":[{"name":"Complement Therapeutics Research Group, Translational and Clinical Research Institute, Newcastle University","place":["Newcastle-upon-Tyne, United Kingdom"]},{"name":"National Renal Complement Therapeutics Centre, The Royal Victoria Infirmary","place":["Newcastle-upon-Tyne, United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Kavanagh","sequence":"additional","affiliation":[{"name":"Complement Therapeutics Research Group, Translational and Clinical Research Institute, Newcastle University","place":["Newcastle-upon-Tyne, United Kingdom"]},{"name":"National Renal Complement Therapeutics Centre, The Royal Victoria Infirmary","place":["Newcastle-upon-Tyne, United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kevin J.","family":"Marchbank","sequence":"additional","affiliation":[{"name":"Complement Therapeutics Research Group, Translational and Clinical Research Institute, Newcastle University","place":["Newcastle-upon-Tyne, United Kingdom"]},{"name":"National Renal Complement Therapeutics Centre, The Royal Victoria Infirmary","place":["Newcastle-upon-Tyne, United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/0167-5699(91)90003-c","article-title":"Complement deficiency and disease","volume":"12","author":"Morgan","year":"1991","journal-title":"Immunol Today"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1007\/s002510050300","article-title":"Three new polymorphisms in the human complement factor H gene and promoter region","volume":"46","author":"Warwicker","year":"1997","journal-title":"Immunogenetics"},{"key":"B3","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1093\/bmb\/ldl004","article-title":"Atypical haemolytic uraemic syndrome","author":"Kavanagh","year":"2006","journal-title":"Br Med Bull"},{"key":"B4","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1016\/j.molimm.2013.05.224","article-title":"Complement therapy in atypical haemolytic uraemic syndrome (Ahus)","volume":"56","author":"Wong","year":"2013","journal-title":"Mol Immunol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2022018833","article-title":"Atypical hemolytic uremic syndrome in the era of terminal complement inhibition: An observational cohort study","volume":"142","author":"Brocklebank","year":"2023","journal-title":"Blood"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.21037\/atm.2018.10.35","article-title":"Targeting properdin in the treatment of atypical haemolytic uraemic syndrome: Better than eculizumab","volume":"6","author":"Smith-Jackson","year":"2018","journal-title":"Ann Transl Med"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1093\/ckj\/sfx081","article-title":"Complement C5-inhibiting therapy for the thrombotic microangiopathies: Accumulating evidence, but not a panacea","volume":"10","author":"Brocklebank","year":"2017","journal-title":"Clin Kidney J"},{"key":"B8","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1007\/s00281-017-0655-8","article-title":"Expanding horizons in complement drug discovery: Challenges and emerging strategies","volume":"40","author":"Harris","year":"2017","journal-title":"Semin Immunopathol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1084\/jem.142.4.856","article-title":"Properdin: Binding to C3b and stabilization of the C3b-dependent C3 convertase","volume":"142","author":"Fearon","year":"1975","journal-title":"J Exp Med"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1042\/bj2350723","article-title":"The C3 convertase of the alternative pathway of human complement. Enzymic properties of the bimolecular proteinase","volume":"235","author":"Pangburn","year":"1986","journal-title":"Biochem J"},{"key":"B11","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1111\/imr.13141","article-title":"Contribution of animal models to the mechanistic understanding of alternative pathway and amplification loop (Ap\/Al)-driven complement-mediated diseases","volume":"313","author":"Gibson","year":"2022","journal-title":"Immunol Rev"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1084\/jem.144.4.1076","article-title":"Alternative pathway of complement: Recruitment of precursor properdin by the labile C3\/C5 convertase and the potentiation of the pathway","volume":"144","author":"Medicus","year":"1976","journal-title":"J Exp Med"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.2004.02627.x","article-title":"The quantitative role of alternative pathway amplification in classical pathway induced terminal complement activation","volume":"138","author":"Harboe","year":"2004","journal-title":"Clin Exp Immunol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2009.09.005","article-title":"The down-stream effects of mannan-induced lectin complement pathway activation depend quantitatively on alternative pathway amplification","volume":"47","author":"Harboe","year":"2009","journal-title":"Mol Immunol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2004.02.005","article-title":"The human complement factor H: Functional roles, genetic variations and disease associations","volume":"41","author":"Rodriguez de Cordoba","year":"2004","journal-title":"Mol Immunol"},{"key":"B16","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1042\/bj2520047","article-title":"Analysis of the interactions between properdin, the third component of complement (C3), and its physiological activation products","volume":"252","author":"Farries","year":"1988","journal-title":"Biochem J"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1309618110","article-title":"Structural basis for the stabilization of the complement alternative pathway C3 convertase by properdin","volume":"110","author":"Alcorlo","year":"2013","journal-title":"Proc Natl Acad Sci USA"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.15252\/embj.201696173","article-title":"Functional and structural insight into properdin control of complement alternative pathway amplification","volume":"36","author":"Pedersen","year":"2017","journal-title":"EMBO J"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2017121244","article-title":"Blocking properdin prevents complement-mediated hemolytic uremic syndrome and systemic thrombophilia","volume":"29","author":"Ueda","year":"2018","journal-title":"J Am Soc Nephrol"},{"key":"B20","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1681\/ASN.2012060571","article-title":"Loss of properdin exacerbates C3 glomerulopathy resulting from factor H deficiency","volume":"24","author":"Ruseva","year":"2013","journal-title":"J Am Soc Nephrol"},{"key":"B21","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1681\/ASN.2012060570","article-title":"Combination of factor H mutation and properdin deficiency causes severe C3 glomerulonephritis","volume":"24","author":"Lesher","year":"2013","journal-title":"J Am Soc Nephrol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1172\/jci99296","article-title":"Hyperfunctional complement C3 promotes C5-dependent atypical hemolytic uremic syndrome in mice","volume":"129","author":"Smith-Jackson","year":"2019","journal-title":"J Clin Invest"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2024.12.016","article-title":"The membrane attack complex drives thrombotic microangiopathy in complement mediated atypical hemolytic uremic syndrome","volume":"107","author":"Smith-Jackson","year":"2025","journal-title":"Kidney Int"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.180.5.3313","article-title":"Properdin plays a protective role in polymicrobial septic peritonitis","volume":"180","author":"Stover","year":"2008","journal-title":"J Immunol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1172\/jci41782","article-title":"Genetic and therapeutic targeting of properdin in mice prevents complement-mediated tissue injury","volume":"120","author":"Kimura","year":"2010","journal-title":"J Clin Invest"},{"key":"B26","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1089\/mab.2014.0066","article-title":"Anti-mouse properdin Tsr 5\/6 monoclonal antibodies block complement alternative pathway-dependent pathogenesis","volume":"34","author":"Bertram","year":"2015","journal-title":"Monoclon Antib Immunodiagn Immunother"},{"key":"B27","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/j.molimm.2015.03.246","article-title":"Atypical ahus: state of the art","volume":"67","author":"Nester","year":"2015","journal-title":"Mol Immunol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20070301","article-title":"Spontaneous hemolytic uremic syndrome triggered by complement factor H lacking surface recognition domains","volume":"204","author":"Pickering","year":"2007","journal-title":"J Exp Med"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-07-728253","article-title":"Murine systemic thrombophilia and hemolytic uremic syndrome from a factor H point mutation","volume":"129","author":"Ueda","year":"2017","journal-title":"Blood"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12466","article-title":"Properdin: A tightly regulated critical inflammatory modulator","volume":"274","author":"Blatt","year":"2016","journal-title":"Immunol Rev"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1701695","article-title":"Statistical validation of rare complement variants provides insights into the molecular basis of atypical hemolytic uremic syndrome and C3 glomerulopathy","volume":"200","author":"Osborne","year":"2018","journal-title":"J Immunol"},{"key":"B32","doi-asserted-by":"publisher","first-page":"1349","DOI":"10.1007\/s00467-018-4042-z","article-title":"The role of properdin in complement-mediated renal diseases: A new player in complement-inhibiting therapy","volume":"34","author":"Michels","year":"2018","journal-title":"Pediatr Nephrol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1202275","article-title":"Blocking properdin, the alternative pathway, and anaphylatoxin receptors ameliorates renal ischemia-reperfusion injury in decay-accelerating factor and Cd59 double-knockout mice","volume":"190","author":"Miwa","year":"2013","journal-title":"J Immunol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2001.0600031018.x","article-title":"Intravenous immunoglobulin protects against experimental thrombotic microangiopathy","volume":"60","author":"Jefferson","year":"2001","journal-title":"Kidney Int"},{"key":"B35","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/j.kint.2019.01.009","article-title":"Differential contribution of C5ar and C5b-9 pathways to renal thrombic microangiopathy and macrovascular thrombosis in mice carrying an atypical hemolytic syndrome-related factor H mutation","volume":"96","author":"Ueda","year":"2019","journal-title":"Kidney Int"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2015030295","article-title":"Partial complement factor H deficiency associates with C3 glomerulopathy and thrombotic microangiopathy","volume":"27","author":"Vernon","year":"2016","journal-title":"J Am Soc Nephrol"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1201751","article-title":"Tissue-specific host recognition by complement factor H is mediated by differential activities of its glycosaminoglycan-binding regions","volume":"190","author":"Clark","year":"2013","journal-title":"J Immunol"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2022.07.035","article-title":"Factor H related proteins modulate complement activation on kidney cells","volume":"102","author":"Renner","year":"2022","journal-title":"Kidney Int"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1300610","article-title":"Identification of a novel mode of complement activation on stimulated platelets mediated by properdin and C3(H2o)","volume":"190","author":"Saggu","year":"2013","journal-title":"J Immunol"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0092404","article-title":"Protective role for properdin in progression of experimental murine atherosclerosis","volume":"9","author":"Steiner","year":"2014","journal-title":"PloS One"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1038\/srep42532","article-title":"The alternative complement pathway is dysregulated in patients with chronic heart failure","volume":"7","author":"Shahini","year":"2017","journal-title":"Sci Rep"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1828298\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T04:48:19Z","timestamp":1777351699000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1828298\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,28]]},"references-count":41,"alternative-id":["10.3389\/fimmu.2026.1828298"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1828298","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,28]]},"article-number":"1828298"}}