{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T08:29:42Z","timestamp":1793608182137,"version":"4.5.0"},"reference-count":41,"publisher":"Elsevier BV","issue":"7","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2027,6,18]],"date-time":"2027-06-18T00:00:00Z","timestamp":1813276800000},"content-version":"am","delay-in-days":352,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"}],"funder":[{"DOI":"10.13039\/501100004053","name":"Masanori Kawano Memorial Public Interest Foundation for Promotion of Pediatrics","doi-asserted-by":"publisher","award":["33-9"],"award-info":[{"award-number":["33-9"]}],"id":[{"id":"10.13039\/501100004053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007449","name":"Takeda Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007449","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100032874","name":"Kawano Masanori Memorial Public Interest Incorporated Foundation for Promotion of Pediatrics","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100032874","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["jthjournal.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Thrombosis and Haemostasis"],"published-print":{"date-parts":[[2026,7]]},"DOI":"10.1016\/j.jtha.2026.02.029","type":"journal-article","created":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T16:59:49Z","timestamp":1773075589000},"page":"2480-2491","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":1,"title":["The C3 p.Ile1157Thr mutation associated with atypical hemolytic uremic syndrome, particularly in Japan, does not lead to disease development in several mouse models"],"prefix":"10.1016","volume":"24","author":[{"given":"Yosuke","family":"Okumura","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4727-6050","authenticated-orcid":false,"given":"Hidemi","family":"Toyoda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mami","family":"Takeoka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichi","family":"Kokame","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu-Wha","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenji","family":"Nishio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Kohso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideo","family":"Wada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isao","family":"Tawara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Hirayama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiyuki","family":"Miyata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.jtha.2026.02.029_bib1","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1056\/NEJMra020528","article-title":"Thrombotic microangiopathies","volume":"347","author":"Moake","year":"2002","journal-title":"N Engl J Med"},{"key":"10.1016\/j.jtha.2026.02.029_bib2","doi-asserted-by":"crossref","first-page":"2836","DOI":"10.1182\/blood-2016-10-709857","article-title":"Thrombotic thrombocytopenic purpura","volume":"129","author":"Joly","year":"2017","journal-title":"Blood"},{"key":"10.1016\/j.jtha.2026.02.029_bib3","doi-asserted-by":"crossref","first-page":"1402","DOI":"10.1056\/NEJMra2108739","article-title":"Shiga toxin-producing Escherichia coli and the hemolytic-uremic syndrome","volume":"389","author":"Freedman","year":"2023","journal-title":"N Engl J Med"},{"key":"10.1016\/j.jtha.2026.02.029_bib4","doi-asserted-by":"crossref","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":"10.1016\/j.jtha.2026.02.029_bib5","doi-asserted-by":"crossref","first-page":"1676","DOI":"10.1056\/NEJMra0902814","article-title":"Atypical hemolytic-uremic syndrome","volume":"361","author":"Noris","year":"2009","journal-title":"N Engl J Med"},{"key":"10.1016\/j.jtha.2026.02.029_bib6","first-page":"400","article-title":"The genetics of atypical hemolytic uremic syndrome","volume":"30","author":"Feitz","year":"2018","journal-title":"Med Genet"},{"key":"10.1016\/j.jtha.2026.02.029_bib7","article-title":"CFH and CFHR structural variants in atypical hemolytic uremic syndrome: prevalence, genomic characterization and impact on outcome","volume":"13","author":"Piras","year":"2022","journal-title":"Front Immunol"},{"key":"10.1016\/j.jtha.2026.02.029_bib8","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1053\/j.ajkd.2015.03.040","article-title":"Glomerular diseases dependent on complement activation, including atypical hemolytic uremic syndrome, membranoproliferative glomerulonephritis, and C3 glomerulopathy: core curriculum 2015","volume":"66","author":"Noris","year":"2015","journal-title":"Am J Kidney Dis"},{"key":"10.1016\/j.jtha.2026.02.029_bib9","doi-asserted-by":"crossref","first-page":"2464","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":"10.1016\/j.jtha.2026.02.029_bib10","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1007\/s10157-018-1549-3","article-title":"Clinical characteristics and genetic backgrounds of Japanese patients with atypical hemolytic uremic syndrome","volume":"22","author":"Fujisawa","year":"2018","journal-title":"Clin Exp Nephrol"},{"key":"10.1016\/j.jtha.2026.02.029_bib11","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0124655","article-title":"A novel quantitative hemolytic assay coupled with restriction fragment length polymorphisms analysis enabled early diagnosis of atypical hemolytic uremic syndrome and identified unique predisposing mutations in Japan","volume":"10","author":"Yoshida","year":"2015","journal-title":"PLoS One"},{"key":"10.1016\/j.jtha.2026.02.029_bib12","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1177\/1076029618771750","article-title":"Clinical manifestation of patients with atypical hemolytic uremic syndrome with the C3 p.I1157T variation in the Kinki Region of Japan","volume":"24","author":"Matsumoto","year":"2018","journal-title":"Clin Appl Thromb Hemost"},{"key":"10.1016\/j.jtha.2026.02.029_bib13","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.molimm.2015.03.248","article-title":"The molecular and structural bases for the association of complement C3 mutations with atypical hemolytic uremic syndrome","volume":"66","author":"Mart\u00ednez-Barricarte","year":"2015","journal-title":"Mol Immunol"},{"key":"10.1016\/j.jtha.2026.02.029_bib14","doi-asserted-by":"crossref","first-page":"1061","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":"10.1016\/j.jtha.2026.02.029_bib15","doi-asserted-by":"crossref","first-page":"99","DOI":"10.5551\/jat.RV17026","article-title":"Pathogenesis of atypical hemolytic uremic syndrome","volume":"26","author":"Yoshida","year":"2019","journal-title":"J Atheroscler Thromb"},{"key":"10.1016\/j.jtha.2026.02.029_bib16","doi-asserted-by":"crossref","first-page":"3161","DOI":"10.1182\/blood-2005-07-2765","article-title":"Complete deficiency in ADAMTS13 is prothrombotic, but it alone is not sufficient to cause thrombotic thrombocytopenic purpura","volume":"107","author":"Banno","year":"2006","journal-title":"Blood"},{"key":"10.1016\/j.jtha.2026.02.029_bib17","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1007\/s12185-023-03668-x","article-title":"Regulation of von Willebrand factor by ADAMTS13 ameliorates lipopolysaccharide-induced lung injury in mice","volume":"118","author":"Onodera","year":"2023","journal-title":"Int J Hematol"},{"key":"10.1016\/j.jtha.2026.02.029_bib18","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1182\/blood.2019001040","article-title":"Synergistic effects of ADAMTS13 deficiency and complement activation in pathogenesis of thrombotic microangiopathy","volume":"134","author":"Zheng","year":"2019","journal-title":"Blood"},{"key":"10.1016\/j.jtha.2026.02.029_bib19","doi-asserted-by":"crossref","first-page":"376","DOI":"10.4049\/jimmunol.132.1.376","article-title":"Complement activation via the alternative pathway by purified Salmonella lipopolysaccharide is affected by its structure but not its O-antigen length","volume":"132","author":"Grossman","year":"1984","journal-title":"J Immunol"},{"key":"10.1016\/j.jtha.2026.02.029_bib20","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.3389\/fimmu.2020.01123","article-title":"Deficiency of mouse FHR-1 homolog, FHR-E, accelerates sepsis, and acute kidney injury through enhancing the LPS-induced alternative complement pathway","volume":"11","author":"Li","year":"2020","journal-title":"Front Immunol"},{"key":"10.1016\/j.jtha.2026.02.029_bib21","doi-asserted-by":"crossref","first-page":"1581","DOI":"10.1007\/s40620-021-01025-x","article-title":"Pregnancy-triggered atypical hemolytic uremic syndrome (aHUS): a Global aHUS Registry analysis","volume":"34","author":"Fakhouri","year":"2021","journal-title":"J Nephrol"},{"key":"10.1016\/j.jtha.2026.02.029_bib22","doi-asserted-by":"crossref","first-page":"1249","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":"10.1016\/j.jtha.2026.02.029_bib23","doi-asserted-by":"crossref","first-page":"1184","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":"10.1016\/j.jtha.2026.02.029_bib24","doi-asserted-by":"crossref","first-page":"2359","DOI":"10.1182\/blood-2014-10-609073","article-title":"Mapping interactions between complement C3 and regulators using mutations in atypical hemolytic uremic syndrome","volume":"125","author":"Schramm","year":"2015","journal-title":"Blood"},{"key":"10.1016\/j.jtha.2026.02.029_bib25","doi-asserted-by":"crossref","DOI":"10.1016\/j.imbio.2023.152687","article-title":"Despite altered immune compartments and increased complement consumption, heterozygous C3 gain-of-function mice do not develop atypical haemolytic syndrome following exposure to various inflammatory stimuli [abstract]","volume":"228","author":"Simpson","year":"2023","journal-title":"Immunobiology"},{"key":"10.1016\/j.jtha.2026.02.029_bib26","doi-asserted-by":"crossref","first-page":"1614","DOI":"10.1016\/j.ekir.2021.03.885","article-title":"Risk of atypical HUS among family members of patients carrying complement regulatory gene abnormality","volume":"6","author":"Ardissino","year":"2021","journal-title":"Kidney Int Rep"},{"key":"10.1016\/j.jtha.2026.02.029_bib27","doi-asserted-by":"crossref","first-page":"S44","DOI":"10.1002\/ajh.26854","article-title":"Complement-driven hemolytic uremic syndrome","volume":"98","author":"Leon","year":"2023","journal-title":"Am J Hematol"},{"key":"10.1016\/j.jtha.2026.02.029_bib28","doi-asserted-by":"crossref","first-page":"1844","DOI":"10.2215\/CJN.02210310","article-title":"Relative role of genetic complement abnormalities in sporadic and familial aHUS and their impact on clinical phenotype","volume":"5","author":"Noris","year":"2010","journal-title":"Clin J Am Soc Nephrol"},{"key":"10.1016\/j.jtha.2026.02.029_bib29","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1016\/S0140-6736(17)30062-4","article-title":"Haemolytic uraemic syndrome","volume":"390","author":"Fakhouri","year":"2017","journal-title":"Lancet"},{"key":"10.1016\/j.jtha.2026.02.029_bib30","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1016\/j.semnephrol.2013.08.003","article-title":"Atypical hemolytic uremic syndrome","volume":"33","author":"Kavanagh","year":"2013","journal-title":"Semin Nephrol"},{"key":"10.1016\/j.jtha.2026.02.029_bib31","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.thromres.2018.08.020","article-title":"Complement activation associated with ADAMTS13 deficiency may contribute to the characteristic glomerular manifestations in Upshaw-Schulman syndrome","volume":"170","author":"Itami","year":"2018","journal-title":"Thromb Res"},{"key":"10.1016\/j.jtha.2026.02.029_bib32","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1111\/bjh.12707","article-title":"Complement and cytokine response in acute thrombotic thrombocytopenic purpura","volume":"164","author":"Westwood","year":"2014","journal-title":"Br J Haematol"},{"key":"10.1016\/j.jtha.2026.02.029_bib33","doi-asserted-by":"crossref","first-page":"e338","DOI":"10.1055\/s-0038-1672189","article-title":"Complement component C3 binds to the A3 domain of von Willebrand factor","volume":"2","author":"Nolasco","year":"2018","journal-title":"TH Open"},{"key":"10.1016\/j.jtha.2026.02.029_bib34","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/j.hoc.2015.01.008","article-title":"Ultralarge von Willebrand factor-induced platelet clumping and activation of the alternative complement pathway in thrombotic thrombocytopenic purpura and the hemolytic-uremic syndromes","volume":"29","author":"Turner","year":"2015","journal-title":"Hematol Oncol Clin North Am"},{"key":"10.1016\/j.jtha.2026.02.029_bib35","doi-asserted-by":"crossref","first-page":"1034","DOI":"10.1182\/blood-2014-06-585430","article-title":"von Willebrand factor is a cofactor in complement regulation","volume":"125","author":"Feng","year":"2015","journal-title":"Blood"},{"key":"10.1016\/j.jtha.2026.02.029_bib36","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/j.molimm.2012.12.006","article-title":"Analysis of genetic and predisposing factors in Japanese patients with atypical hemolytic uremic syndrome","volume":"54","author":"Fan","year":"2013","journal-title":"Mol Immunol"},{"key":"10.1016\/j.jtha.2026.02.029_bib37","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1007\/s12185-014-1655-2","article-title":"Analysis of patients with atypical hemolytic uremic syndrome treated at the Mie University Hospital: concentration of C3 p.I1157T mutation","volume":"100","author":"Matsumoto","year":"2014","journal-title":"Int J Hematol"},{"key":"10.1016\/j.jtha.2026.02.029_bib38","doi-asserted-by":"crossref","DOI":"10.1016\/j.cellimm.2024.104886","article-title":"Complement system component 3 deficiency modulates the phenotypic profile of murine macrophages","volume":"405-406","author":"Francisco da Silva","year":"2024","journal-title":"Cell Immunol"},{"key":"10.1016\/j.jtha.2026.02.029_bib39","doi-asserted-by":"crossref","DOI":"10.1128\/mBio.01753-18","article-title":"Complement activation contributes to severe acute respiratory syndrome coronavirus pathogenesis","volume":"9","author":"Gralinski","year":"2018","journal-title":"mBio"},{"key":"10.1016\/j.jtha.2026.02.029_bib40","doi-asserted-by":"crossref","first-page":"11490","DOI":"10.1073\/pnas.92.25.11490","article-title":"Studies of group B streptococcal infection in mice deficient in complement component C3 or C4 demonstrate an essential role for complement in both innate and acquired immunity","volume":"92","author":"Wessels","year":"1995","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.jtha.2026.02.029_bib41","doi-asserted-by":"crossref","first-page":"1386","DOI":"10.1038\/nm.2847","article-title":"Infection-induced NETosis is a dynamic process involving neutrophil multitasking in vivo","volume":"18","author":"Yipp","year":"2012","journal-title":"Nat Med"}],"container-title":["Journal of Thrombosis and Haemostasis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1538783626001492?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1538783626001492?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T08:11:36Z","timestamp":1793607096000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1538783626001492"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7]]},"references-count":41,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["S1538783626001492"],"URL":"https:\/\/doi.org\/10.1016\/j.jtha.2026.02.029","relation":{},"ISSN":["1538-7836"],"issn-type":[{"value":"1538-7836","type":"print"}],"subject":[],"published":{"date-parts":[[2026,7]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"The C3 p.Ile1157Thr mutation associated with atypical hemolytic uremic syndrome, particularly in Japan, does not lead to disease development in several mouse models","name":"articletitle","label":"Article Title"},{"value":"Journal of Thrombosis and Haemostasis","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jtha.2026.02.029","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}]}}