{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T04:00:27Z","timestamp":1792036827059,"version":"4.4.0"},"reference-count":45,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2004,1,1]],"date-time":"2004-01-01T00:00:00Z","timestamp":1072915200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2004,1,1]],"date-time":"2004-01-01T00:00:00Z","timestamp":1072915200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Seminars in Hematology"],"published-print":{"date-parts":[[2004,1]]},"DOI":"10.1053\/j.seminhematol.2003.11.016","type":"journal-article","created":{"date-parts":[[2004,2,10]],"date-time":"2004-02-10T10:35:52Z","timestamp":1076409352000},"page":"82-88","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":140,"special_numbering":"S1","title":["Environmental and genetic factors influencing inhibitor development"],"prefix":"10.1053","volume":"41","author":[{"given":"Johannes","family":"Oldenburg","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f6rg","family":"Schr\u00f6der","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans","family":"Hermann Brackmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clemens","family":"M\u00fcller-Reible","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rainer","family":"Schwaab","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward","family":"Tuddenham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"suppl","key":"10.1053\/j.seminhematol.2003.11.016_BIB1","article-title":"Increased frequency of inhibitors in African American haemophilia A patients. ASH Nashville","volume":"239","author":"Addiego","year":"1994","journal-title":"Blood"},{"key":"10.1053\/j.seminhematol.2003.11.016_BIB2","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1111\/j.1365-2141.1990.tb07878.x","article-title":"Histocompatibility antigen patterns in haemophilic patients with factor VIII antibodies","volume":"76","author":"Aly","year":"1990","journal-title":"Br J Haematol"},{"key":"10.1053\/j.seminhematol.2003.11.016_BIB3","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1046\/j.1365-2516.2001.00510.x","article-title":"The Malmo International Brother Study (MIBS)","volume":"7","author":"Astermark","year":"2001","journal-title":"Haemophilia"},{"key":"10.1053\/j.seminhematol.2003.11.016_BIB4","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1182\/blood.V95.2.564","article-title":"Reduction of the antigenicity of factor VIII toward complex inhibitory antibody plasmas using multiply-substituted hybrid human\/porcine factor VIII molecules","volume":"95","author":"Barrow","year":"2000","journal-title":"Blood"},{"key":"10.1053\/j.seminhematol.2003.11.016_BIB5","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1046\/j.1365-2516.2002.00635.x","article-title":"Continuous infusion of coagulation factors","volume":"8","author":"Batorova","year":"2002","journal-title":"Haemophilia"},{"key":"10.1053\/j.seminhematol.2003.11.016_BIB6","first-page":"657","article-title":"Characterization of the factor VIII defect in 147 patients with sporadic hemophilia A","volume":"58","author":"Becker","year":"1996","journal-title":"Am J Hum Genet"},{"key":"10.1053\/j.seminhematol.2003.11.016_BIB7","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1084\/jem.178.1.27","article-title":"Specifity and promiscuity among naturally processed peptides bound to HLA-DR alleles","volume":"178","author":"Chicz","year":"1993","journal-title":"J Exp Med"},{"key":"10.1053\/j.seminhematol.2003.11.016_BIB8","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1055\/s-0037-1615871","article-title":"The role of genetics in inhibitor formation","volume":"82","author":"Cox-Gill","year":"1999","journal-title":"Thromb Haemost"},{"key":"10.1053\/j.seminhematol.2003.11.016_BIB9","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1111\/j.1600-0609.1979.tb02856.x","article-title":"Development of factor VIII antibody in haemophilic monozygotic twins","volume":"23","year":"1979","journal-title":"Scand J Haematol"},{"key":"10.1053\/j.seminhematol.2003.11.016_BIB10","doi-asserted-by":"crossref","first-page":"2347","DOI":"10.1182\/blood.V91.7.2347","article-title":"A human alloantibody interferes with binding of factor IXa to the factor VIII light chain","volume":"91","author":"Fijnvandraat","year":"1998","journal-title":"Blood"},{"key":"10.1053\/j.seminhematol.2003.11.016_BIB11","doi-asserted-by":"crossref","first-page":"4371","DOI":"10.1182\/blood.V89.12.4371","article-title":"The missense mutation Arg593\u2192Cys is related to antibody formation in a patient with mild haemophilia A","volume":"89","author":"Fijnvandraat","year":"1997","journal-title":"Blood"},{"key":"10.1053\/j.seminhematol.2003.11.016_BIB12","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1097\/00001721-199003000-00003","article-title":"A murine monoclonal anti-factor VIII inhibitory antibody and two human factor VIII inhibitors bind to different areas within a twenty amino acid segment of the acidic region of factor VIII heavy chain","volume":"1","author":"Foster","year":"1990","journal-title":"Blood Coagul Fibrinolysis"},{"key":"10.1053\/j.seminhematol.2003.11.016_BIB13","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1055\/s-0038-1653453","article-title":"HLA antigens and factor VIII antibody in classic haemophilia. European Study Group of Factor VIII Antibody","volume":"46","author":"Frommel","year":"1981","journal-title":"Thromb Haemost"},{"key":"10.1053\/j.seminhematol.2003.11.016_BIB14","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1093\/nar\/26.1.265","article-title":"Haemophilia B","volume":"26","author":"Gianelli","year":"1998","journal-title":"Nucleic Acids Res"},{"key":"10.1053\/j.seminhematol.2003.11.016_BIB15","first-page":"228","article-title":"Safety and immunogenicity of recombinant factor VIII (Recombinate) in previously untreated patients (PUPs). A 7.3 year update. WFH The Hague","volume":"4","author":"Gruppo","year":"1998","journal-title":"Haemophilia"},{"key":"10.1053\/j.seminhematol.2003.11.016_BIB16","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1055\/s-0037-1615061","article-title":"Factor VIII inhibitors in mild and moderate-severity haemophilia A. UK Haemophilia Centre Directors Organisation","volume":"79","author":"Hay","year":"1998","journal-title":"Thromb Haemost"},{"key":"10.1053\/j.seminhematol.2003.11.016_BIB17","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1055\/s-0038-1655944","article-title":"HLA class II profile","volume":"77","author":"Hay","year":"1997","journal-title":"Thromb Haemost"},{"key":"10.1053\/j.seminhematol.2003.11.016_BIB18","doi-asserted-by":"crossref","first-page":"3701","DOI":"10.1182\/blood.V92.10.3701","article-title":"Residues Glu2181-Val2243 contain a major determinant of the inhibitory epitope in the C2 domain of human factor VIII","volume":"92","author":"Healey","year":"1998","journal-title":"Blood"},{"key":"10.1053\/j.seminhematol.2003.11.016_BIB19","doi-asserted-by":"crossref","first-page":"14505","DOI":"10.1074\/jbc.270.24.14505","article-title":"Residues 484\u2013508 contain a major determinant of the inhibitory epitope in the A2 domain of human factor VIII","volume":"270","author":"Healey","year":"1995","journal-title":"J Biol Chem"},{"key":"10.1053\/j.seminhematol.2003.11.016_BIB20","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1182\/blood.V95.1.156","article-title":"A human antibody directed to the factor VIII C1 domain inhibits factor VIII cofactor activity and binding to von Willebrand factor","volume":"95","author":"Jacquemin","year":"2000","journal-title":"Blood"},{"key":"10.1053\/j.seminhematol.2003.11.016_BIB21","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1182\/blood.V96.3.958","article-title":"A novel cause of mild\/moderate haemophilia A","volume":"96","author":"Jacquemin","year":"2000","journal-title":"Blood"},{"key":"10.1053\/j.seminhematol.2003.11.016_BIB22","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1093\/nar\/26.1.216","article-title":"The factor VIII structure and mutation resource site","volume":"26","author":"Kemball-Cook","year":"1998","journal-title":"Nucleic Acid Res"},{"key":"10.1053\/j.seminhematol.2003.11.016_BIB23","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1055\/s-2007-1000659","article-title":"Factor VIII inhibitors in patients with haemophilia A","volume":"21","author":"Kreuz","year":"1995","journal-title":"Semin Thromb Haemost"},{"key":"10.1053\/j.seminhematol.2003.11.016_BIB24","doi-asserted-by":"crossref","first-page":"3983","DOI":"10.1182\/blood.V92.11.3983","article-title":"The life cycle of coagulation factor VIII in view of its structure and function","volume":"92","author":"Lenting","year":"1998","journal-title":"Blood"},{"key":"10.1053\/j.seminhematol.2003.11.016_BIB25","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1046\/j.1365-2516.1998.440350.x","article-title":"The molecular basis of haemophilia B","volume":"4","author":"Lillicrap","year":"1998","journal-title":"Haemophilia"},{"key":"10.1053\/j.seminhematol.2003.11.016_BIB26","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1055\/s-0038-1647359","article-title":"Relationship of major histocompatibility complex class II genes to inhibitor antibody formation in haemophilia A","volume":"64","author":"Lippert","year":"1990","journal-title":"Thromb Haemost"},{"key":"10.1053\/j.seminhematol.2003.11.016_BIB27","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1182\/blood.V96.3.979","article-title":"Haemophilic factor VIII C1- and C2-domain missense mutations and their modeling to the 1.5-angstrom human C2-domain crystal structure","volume":"96","author":"Liu","year":"2000","journal-title":"Blood"},{"issue":"suppl 1","key":"10.1053\/j.seminhematol.2003.11.016_BIB28","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1159\/000204029","article-title":"Gene mutations and inhibitor formation in patients with hemophilia B","volume":"94","author":"Ljung","year":"1995","journal-title":"Acta Haematol"},{"key":"10.1053\/j.seminhematol.2003.11.016_BIB29","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1046\/j.1365-2141.2001.02828.x","article-title":"Incidence of factor VIII inhibitors in severe haemophilia","volume":"113","author":"Lorenzo","year":"2001","journal-title":"Br J Haematol"},{"issue":"suppl","key":"10.1053\/j.seminhematol.2003.11.016_BIB30","article-title":"Recombinant FVIII (Kogenate) treatment of previously untreated patients (PUPs) with haemophilia A. Update of safety, efficacy and inhibitor development after seven study years. ISTH Florence","volume":"162","author":"Lusher","year":"1997","journal-title":"Thromb Haemost"},{"key":"10.1053\/j.seminhematol.2003.11.016_BIB31","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1055\/s-0038-1661081","article-title":"HLA-DR and factor VIII antibodies in haemophilia A","volume":"51","author":"Mayr","year":"1984","journal-title":"Thromb Haemost"},{"issue":"suppl","key":"10.1053\/j.seminhematol.2003.11.016_BIB32","first-page":"7","article-title":"Risk factors for inhibitor development in haemophilia A","volume":"85","author":"Oldenburg","year":"2000","journal-title":"Haematologica"},{"key":"10.1053\/j.seminhematol.2003.11.016_BIB33","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1055\/s-0038-1655945","article-title":"HLA genotype of patients with severe haemophilia A due to intron 22 inversion with and without inhibitors to factor VIII","volume":"77","author":"Oldenburg","year":"1997","journal-title":"Thromb Haemost"},{"key":"10.1053\/j.seminhematol.2003.11.016_BIB34","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1055\/s-0037-1615015","article-title":"Small deletion\/insertion mutations within poly-A-runs of the factor VIII gene mitigate the severe haemophilia A phenotype","volume":"79","author":"Oldenburg","year":"1998","journal-title":"Thromb Haemost"},{"key":"10.1053\/j.seminhematol.2003.11.016_BIB34A","series-title":"Genetic basis of inhibitor development in severe haemophilia A and B","first-page":"21","author":"Oldenburg","year":"2002"},{"key":"10.1053\/j.seminhematol.2003.11.016_BIB35","doi-asserted-by":"crossref","first-page":"2267","DOI":"10.1182\/blood.V93.7.2267","article-title":"Antifactor VIII antibody inhibiting allogeneic but not autologous factor VIII in patients with mild haemophilia A","volume":"93","author":"Peerlinck","year":"1999","journal-title":"Blood"},{"key":"10.1053\/j.seminhematol.2003.11.016_BIB36","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1038\/46601","article-title":"Structure of the C2 domain of human factor VIII at 1.5 A resolution","volume":"402","author":"Pratt","year":"1999","journal-title":"Nature"},{"key":"10.1053\/j.seminhematol.2003.11.016_BIB37","doi-asserted-by":"crossref","first-page":"1811","DOI":"10.1182\/blood.V86.5.1811.bloodjournal8651811","article-title":"Some factor VIII inhibitor antibodies recognize a common epitope corresponding to C2 domain amino acids 2248 through 2312, which overlap a phospholipid-binding site","volume":"86","author":"Scandella","year":"1995","journal-title":"Blood"},{"key":"10.1053\/j.seminhematol.2003.11.016_BIB38","doi-asserted-by":"crossref","first-page":"1618","DOI":"10.1182\/blood.V74.5.1618.1618","article-title":"Localization of epitopes for human factor VIII inhibitor antibodies by immunoblotting and antibody neutralization","volume":"74","author":"Scandella","year":"1989","journal-title":"Blood"},{"key":"10.1053\/j.seminhematol.2003.11.016_BIB39","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1046\/j.1365-2516.1999.00300.x","article-title":"Incidence of inhibitors in haemophilia A patients\u2014A review of recent studies of recombinant and plasma-derived factor VIII concentrates","volume":"5","author":"Scharrer","year":"1999","journal-title":"Haemophilia"},{"key":"10.1053\/j.seminhematol.2003.11.016_BIB40","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1097\/00001721-199310000-00012","article-title":"Incidence of inhibitors in haemophiliacs. A review of the literature","volume":"4","author":"Scharrer","year":"1993","journal-title":"Blood Coagul Fibrinolysis"},{"key":"10.1053\/j.seminhematol.2003.11.016_BIB41","doi-asserted-by":"crossref","first-page":"1402","DOI":"10.1055\/s-0038-1649954","article-title":"Haemophilia A","volume":"74","author":"Schwaab","year":"1995","journal-title":"Thromb Haemost"},{"key":"10.1053\/j.seminhematol.2003.11.016_BIB42","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1046\/j.1538-7836.2003.00230.x","article-title":"Intensive exposure to factor VIII is a risk factor for inhibitor development in mild hemophilia A","volume":"1","author":"Sharathkumar","year":"2003","journal-title":"J Thromb Haemost"},{"key":"10.1053\/j.seminhematol.2003.11.016_BIB43","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/0049-3848(92)90161-3","article-title":"Characterization of a factor VIII immunogenic site using factor VIII synthetic peptide 1687\u20131695 and rabbit anti-peptide antibodies","volume":"65","author":"Tiarks","year":"1992","journal-title":"Thromb Res"},{"key":"10.1053\/j.seminhematol.2003.11.016_BIB44","first-page":"565","article-title":"Partial correction of a severe molecular defect in haemophilia A, because of errors during expression of the factor VIII gene","volume":"60","author":"Young","year":"1997","journal-title":"Am J Hum Genet"}],"container-title":["Seminars in Hematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S003719630300310X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S003719630300310X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T06:12:30Z","timestamp":1758521550000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S003719630300310X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,1]]},"references-count":45,"alternative-id":["S003719630300310X"],"URL":"https:\/\/doi.org\/10.1053\/j.seminhematol.2003.11.016","relation":{},"ISSN":["0037-1963"],"issn-type":[{"value":"0037-1963","type":"print"}],"subject":[],"published":{"date-parts":[[2004,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Environmental and genetic factors influencing inhibitor development","name":"articletitle","label":"Article Title"},{"value":"Seminars in Hematology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1053\/j.seminhematol.2003.11.016","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"converted-article","name":"content_type","label":"Content Type"},{"value":"Copyright \u00a9 2004 Elsevier Inc. All rights reserved.","name":"copyright","label":"Copyright"}]}}