{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T13:08:29Z","timestamp":1790687309936,"version":"4.1.0"},"reference-count":197,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2020,1,10]],"date-time":"2020-01-10T00:00:00Z","timestamp":1578614400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"DOI":"10.3389\/fimmu.2019.02991","type":"journal-article","created":{"date-parts":[[2020,1,10]],"date-time":"2020-01-10T04:29:43Z","timestamp":1578630583000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":59,"title":["Tolerating Factor VIII: Recent Progress"],"prefix":"10.3389","volume":"10","author":[{"given":"Sebastien","family":"Lacroix-Desmazes","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Voorberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Lillicrap","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David W.","family":"Scott","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen P.","family":"Pratt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2020,1,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"4046","DOI":"10.1182\/blood-2012-09-457036","article-title":"Intensity of factor VIII treatment and inhibitor development in children with severe hemophilia A: the RODIN study","volume":"121","author":"Gouw","year":"2013","journal-title":"Blood"},{"key":"B2","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1111\/jth.13888","article-title":"Timing and severity of inhibitor development in recombinant versus plasma-derived factor VIII concentrates: a SIPPET analysis","volume":"16","author":"Peyvandi","year":"2018","journal-title":"J Thromb Haemost"},{"key":"B3","doi-asserted-by":"publisher","first-page":"6367","DOI":"10.1182\/blood-2010-09-308668","article-title":"Incidence of factor VIII inhibitors throughout life in severe hemophilia A in the United Kingdom","volume":"117","author":"Hay","year":"2011","journal-title":"Blood"},{"key":"B4","doi-asserted-by":"publisher","first-page":"143","DOI":"10.2147\/JBM.S77332","article-title":"Acquired hemophilia A: emerging treatment options","volume":"6","author":"Janbain","year":"2015","journal-title":"J Blood Med"},{"key":"B5","doi-asserted-by":"publisher","first-page":"568","DOI":"10.1055\/s-0037-1613257","article-title":"Distribution of Th1- and Th2-induced anti-factor VIII IgG subclasses in congenital and acquired hemophilia patients","volume":"88","author":"Reding","year":"2002","journal-title":"Thromb Haemost"},{"key":"B6","doi-asserted-by":"publisher","first-page":"558","DOI":"10.1182\/blood.V95.2.558","article-title":"Human antibodies with specificity for the C2 domain of factor VIII are derived from VH1 germline genes","volume":"95","author":"Van Den Brink","year":"2000","journal-title":"Blood"},{"key":"B7","doi-asserted-by":"publisher","first-page":"809","DOI":"10.1056\/NEJMoa1703068","article-title":"Emicizumab prophylaxis in hemophilia A with Inhibitors","volume":"377","author":"Oldenburg","year":"2017","journal-title":"N Engl J Med"},{"key":"B8","doi-asserted-by":"publisher","first-page":"811","DOI":"10.1056\/NEJMoa1803550","article-title":"Emicizumab prophylaxis in patients who have hemophilia A without inhibitors","volume":"379","author":"Mahlangu","year":"2018","journal-title":"N Engl J Med"},{"key":"B9","doi-asserted-by":"publisher","first-page":"1973","DOI":"10.1182\/blood.2019001542","article-title":"Subcutaneous concizumab prophylaxis in hemophilia A and hemophilia A\/B with inhibitors: Phase 2 trial results","volume":"134","author":"Shapiro","year":"2019","journal-title":"Blood"},{"key":"B10","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1053\/j.seminhematol.2013.03.023","article-title":"Animal models of hemophilia and related bleeding disorders","volume":"50","author":"Lozier","year":"2013","journal-title":"Semin Hematol"},{"key":"B11","doi-asserted-by":"publisher","first-page":"S172","DOI":"10.1038\/515S172a","article-title":"Animal models: dogged pursuit","volume":"515","author":"Sohn","year":"2014","journal-title":"Nature"},{"key":"B12","doi-asserted-by":"publisher","first-page":"894","DOI":"10.1111\/jth.13301","article-title":"Canine models of inherited bleeding disorders in the development of coagulation assays, novel protein replacement and gene therapies","volume":"14","author":"Nichols","year":"2016","journal-title":"J Thromb Haemost"},{"key":"B13","doi-asserted-by":"publisher","first-page":"1121","DOI":"10.1111\/jth.13331","article-title":"Gene therapy for immune tolerance induction in hemophilia with inhibitors","volume":"14","author":"Arruda","year":"2016","journal-title":"J Thromb Haemost"},{"key":"B14","doi-asserted-by":"publisher","first-page":"1335","DOI":"10.1182\/blood-2011-08-369132","article-title":"The principal results of the International Immune Tolerance Study: a randomized dose comparison","volume":"119","author":"Hay","year":"2012","journal-title":"Blood"},{"key":"B15","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1016\/j.blre.2018.02.003","article-title":"Review of immune tolerance induction in hemophilia A","volume":"32","author":"Schep","year":"2018","journal-title":"Blood Rev"},{"key":"B16","doi-asserted-by":"publisher","first-page":"2223","DOI":"10.1182\/blood-2010-06-293324","article-title":"Effect of B-cell depletion using anti-CD20 therapy on inhibitory antibody formation to human FVIII in hemophilia A mice","volume":"117","author":"Zhang","year":"2011","journal-title":"Blood"},{"key":"B17","doi-asserted-by":"publisher","first-page":"3415","DOI":"10.1182\/blood-2005-03-1182","article-title":"High-dose factor VIII inhibits factor VIII-specific memory B cells in hemophilia A with factor VIII inhibitors","volume":"106","author":"Hausl","year":"2005","journal-title":"Blood"},{"key":"B18","doi-asserted-by":"publisher","first-page":"612","DOI":"10.1055\/s-0039-1689482","article-title":"Proceedings: A more uniform measurement of factor VIII inhibitors","volume":"34","author":"Kasper","year":"1975","journal-title":"Thromb Diath Haemorrh"},{"key":"B19","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1055\/s-0038-1653759","article-title":"The Nijmegen modification of the Bethesda assay for factor VIII:C inhibitors: improved specificity and reliability","volume":"73","author":"Verbruggen","year":"1995","journal-title":"Thromb Haemost"},{"key":"B20","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1007\/s12016-009-8119-0","article-title":"Characteristics, mechanisms of action, and epitope mapping of anti-factor VIII antibodies","volume":"37","author":"Lavigne-Lissalde","year":"2009","journal-title":"Clin Rev Allergy Immunol"},{"key":"B21","doi-asserted-by":"publisher","first-page":"1039","DOI":"10.1182\/blood-2012-07-444877","article-title":"Distinct characteristics of antibody responses against factor VIII in healthy individuals and in different cohorts of hemophilia A patients","volume":"121","author":"Whelan","year":"2013","journal-title":"Blood"},{"key":"B22","doi-asserted-by":"publisher","first-page":"1180","DOI":"10.1182\/blood-2014-09-598268","article-title":"Affinity of FVIII-specific antibodies reveals major differences between neutralizing and nonneutralizing antibodies in humans","volume":"125","author":"Hofbauer","year":"2015","journal-title":"Blood"},{"key":"B23","doi-asserted-by":"publisher","first-page":"e61120","DOI":"10.1371\/journal.pone.0061120","article-title":"Phenotypes of allo- and autoimmune antibody responses to FVIII characterized by surface plasmon resonance","volume":"8","author":"Lewis","year":"2013","journal-title":"PLoS ONE"},{"key":"B24","doi-asserted-by":"publisher","first-page":"2587","DOI":"10.1182\/blood-2008-08-174987","article-title":"Quantitation of anti-factor VIII antibodies in human plasma","volume":"113","author":"Krudysz-Amblo","year":"2009","journal-title":"Blood"},{"key":"B25","doi-asserted-by":"publisher","first-page":"372","DOI":"10.1182\/asheducation.V2014.1.372.3884771","article-title":"Risky business of inhibitors: HLA haplotypes, gene polymorphisms, and immune responses","volume":"2014","author":"Reipert","year":"2014","journal-title":"Hematol Am Soc Hematol Educ Program"},{"key":"B26","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1111\/jth.12065","article-title":"Dangerous liaisons: how the immune system deals with factor VIII","volume":"11","author":"Wroblewska","year":"2013","journal-title":"J Thromb Haemost"},{"key":"B27","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1111\/jth.12768","article-title":"Characterization of the anti-factor VIII immunoglobulin profile in patients with hemophilia A by use of a fluorescence-based immunoassay","volume":"13","author":"Boylan","year":"2015","journal-title":"J Thromb Haemost"},{"key":"B28","doi-asserted-by":"publisher","first-page":"3795","DOI":"10.1073\/pnas.89.9.3795","article-title":"Natural antibodies to factor VIII. (anti-hemophilic factor) in healthy individuals","volume":"89","author":"Algiman","year":"1992","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B29","doi-asserted-by":"publisher","first-page":"1496","DOI":"10.1172\/JCI117489","article-title":"Healthy subjects produce both anti-factor VIII and specific anti-idiotypic antibodies","volume":"94","author":"Gilles","year":"1994","journal-title":"J Clin Invest"},{"key":"B30","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1016\/S1568-9972(01)00017-9","article-title":"Autoantibodies to factor VIII","volume":"1","author":"Lacroix-Desmazes","year":"2002","journal-title":"Autoimmun Rev"},{"key":"B31","doi-asserted-by":"publisher","first-page":"1131","DOI":"10.1182\/blood-2019-124743","article-title":"Neutralizing and non-neutralizing anti-FVIII antibodies in black and white hemophilia a subjects: a natural history profile","volume":"134","author":"Pratt","year":"2019","journal-title":"Blood"},{"key":"B32","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1182\/blood-2008-02-124941","article-title":"Dynamics of factor VIII interactions determine its immunologic fate in hemophilia A","volume":"112","author":"Lacroix-Desmazes","year":"2008","journal-title":"Blood"},{"key":"B33","doi-asserted-by":"publisher","first-page":"236","DOI":"10.3324\/haematol.2018.206383","article-title":"Pathogenic immune response to therapeutic factor VIII: exacerbated response or failed induction of tolerance?","volume":"104","author":"Varthaman","year":"2019","journal-title":"Haematologica"},{"key":"B34","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1016\/j.blre.2017.07.001","article-title":"To serve and protect: the modulatory role of von Willebrand factor on factor VIII immunogenicity","volume":"31","author":"Hartholt","year":"2017","journal-title":"Blood Rev"},{"key":"B35","doi-asserted-by":"publisher","first-page":"606","DOI":"10.1038\/nri1669","article-title":"Structure and function of the spleen","volume":"5","author":"Mebius","year":"2005","journal-title":"Nat Rev Immunol"},{"key":"B36","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1038\/s41577-018-0088-1","article-title":"Dendritic cell subsets in T cell programming: location dictates function","volume":"19","author":"Eisenbarth","year":"2019","journal-title":"Nat Rev Immunol"},{"key":"B37","doi-asserted-by":"publisher","first-page":"eaau6085","DOI":"10.1126\/sciimmunol.aau6085","article-title":"Structure and function of the immune system in the spleen","volume":"4","author":"Lewis","year":"2019","journal-title":"Sci Immunol"},{"key":"B38","doi-asserted-by":"publisher","first-page":"1816","DOI":"10.1111\/j.1538-7836.2009.03571.x","article-title":"Splenic marginal zone antigen-presenting cells are critical for the primary allo-immune response to therapeutic factor VIII in hemophilia A","volume":"7","author":"Navarrete","year":"2009","journal-title":"J Thromb Haemost"},{"key":"B39","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1111\/jth.13936","article-title":"Early cellular interactions and immune transcriptome profiles in human factor VIII-exposed hemophilia A mice","volume":"16","author":"Lai","year":"2018","journal-title":"J Thromb Haemost"},{"key":"B40","doi-asserted-by":"publisher","first-page":"2559","DOI":"10.1182\/blood-2017-05-782912","article-title":"Marginal zone B cells are critical to factor VIII inhibitor formation in mice with hemophilia A","volume":"130","author":"Zerra","year":"2017","journal-title":"Blood"},{"key":"B41","doi-asserted-by":"publisher","first-page":"1046","DOI":"10.3324\/haematol.2018.200279","article-title":"Prevention of the anti-factor VIII memory B-cell response by inhibition of Bruton tyrosine kinase in experimental hemophilia A","volume":"104","author":"Delignat","year":"2019","journal-title":"Haematologica"},{"key":"B42","doi-asserted-by":"publisher","first-page":"17341","DOI":"10.1074\/jbc.M710360200","article-title":"The human hyaluronan receptor for endocytosis. (HARE\/Stabilin-2) is a systemic clearance receptor for heparin","volume":"283","author":"Harris","year":"2008","journal-title":"J Biol Chem."},{"key":"B43","doi-asserted-by":"publisher","first-page":"3099","DOI":"10.1182\/bloodadvances.2019000650","article-title":"Induction of activated T follicular helper cells is critical for anti-FVIII inhibitor development in hemophilia A mice","volume":"3","author":"Jing","year":"2019","journal-title":"Blood Adv"},{"key":"B44","doi-asserted-by":"publisher","first-page":"1704","DOI":"10.1182\/blood-2008-01-133181","article-title":"Macrophages contribute to the cellular uptake of von Willebrand factor and factor VIII in vivo","volume":"112","author":"Van Schooten","year":"2008","journal-title":"Blood"},{"key":"B45","doi-asserted-by":"publisher","first-page":"4057","DOI":"10.1172\/JCI96400","article-title":"The endothelial cell receptor stabilin-2 regulates VWF-FVIII complex half-life and immunogenicity","volume":"128","author":"Swystun","year":"2018","journal-title":"J Clin Invest"},{"key":"B46","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1038\/cmi.2016.5","article-title":"Immunological functions of liver sinusoidal endothelial cells","volume":"13","author":"Knolle","year":"2016","journal-title":"Cell Mol Immunol"},{"key":"B47","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/j.blre.2011.10.001","article-title":"Requirements for immune recognition and processing of factor VIII by antigen-presenting cells","volume":"26","author":"Van Haren","year":"2012","journal-title":"Blood Rev"},{"key":"B48","doi-asserted-by":"publisher","first-page":"8965","DOI":"10.1073\/pnas.0702120104","article-title":"A role for exposed mannosylations in presentation of human therapeutic self-proteins to CD4+ T lymphocytes","volume":"104","author":"Dasgupta","year":"2007","journal-title":"Proc Natl Acad Sci USA"},{"key":"B49","doi-asserted-by":"publisher","first-page":"23734","DOI":"10.1074\/jbc.274.34.23734","article-title":"The light chain of factor VIII comprises a binding site for low density lipoprotein receptor-related protein","volume":"274","author":"Lenting","year":"1999","journal-title":"J Biol Chem"},{"key":"B50","doi-asserted-by":"publisher","first-page":"37685","DOI":"10.1074\/jbc.274.53.37685","article-title":"Role of the low density lipoprotein-related protein receptor in mediation of factor VIII catabolism","volume":"274","author":"Saenko","year":"1999","journal-title":"J Biol Chem"},{"key":"B51","doi-asserted-by":"publisher","first-page":"83","DOI":"10.3324\/haematol.11535","article-title":"Factor VIII bypasses CD91\/LRP for endocytosis by dendritic cells leading to T-cell activation","volume":"93","author":"Dasgupta","year":"2008","journal-title":"Haematologica"},{"key":"B52","doi-asserted-by":"publisher","first-page":"501","DOI":"10.1016\/j.jaci.2011.08.029","article-title":"Uptake of blood coagulation factor VIII by dendritic cells is mediated via its C1 domain","volume":"129","author":"Herczenik","year":"2012","journal-title":"J Allergy Clin Immunol."},{"key":"B53","doi-asserted-by":"publisher","first-page":"1592","DOI":"10.1111\/jth.14204","article-title":"In-depth comparison of N-glycosylation of human plasma-derived factor VIII and different recombinant products: from structure to clinical implications","volume":"16","author":"Canis","year":"2018","journal-title":"J Thromb Haemost."},{"key":"B54","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1016\/j.thromres.2012.09.011","article-title":"Characterisation of the post-translational modifications of a novel, human cell line-derived recombinant human factor VIII","volume":"131","author":"Kannicht","year":"2013","journal-title":"Thromb Res"},{"key":"B55","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1111\/j.1365-2516.2011.02679.x","article-title":"Immunoprotective effect of von Willebrand factor towards therapeutic factor VIII in experimental haemophilia A","volume":"18","author":"Delignat","year":"2012","journal-title":"Haemophilia"},{"key":"B56","doi-asserted-by":"publisher","first-page":"5294","DOI":"10.1182\/blood-2011-11-391680","article-title":"Modification of an exposed loop in the C1 domain reduces immune responses to factor VIII in hemophilia A mice","volume":"119","author":"Wroblewska","year":"2012","journal-title":"Blood"},{"key":"B57","doi-asserted-by":"publisher","first-page":"271","DOI":"10.3324\/haematol.2016.148502","article-title":"The C1 and C2 domains of blood coagulation factor VIII mediate its endocytosis by dendritic cells","volume":"102","author":"Gangadharan","year":"2017","journal-title":"Haematologica"},{"key":"B58","doi-asserted-by":"publisher","first-page":"351","DOI":"10.3324\/haematol.2017.165720","article-title":"Complement C3 is a novel modulator of the anti-factor VIII immune response","volume":"103","author":"Rayes","year":"2018","journal-title":"Haematologica"},{"key":"B59","doi-asserted-by":"publisher","first-page":"610","DOI":"10.1182\/blood-2006-05-022756","article-title":"VWF protects FVIII from endocytosis by dendritic cells and subsequent presentation to immune effectors","volume":"109","author":"Dasgupta","year":"2007","journal-title":"Blood"},{"key":"B60","doi-asserted-by":"publisher","first-page":"309","DOI":"10.3324\/haematol.2015.137067","article-title":"von Willebrand factor binds to the surface of dendritic cells and modulates peptide presentation of factor VIII","volume":"101","author":"Sorvillo","year":"2016","journal-title":"Haematologica"},{"key":"B61","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/j.cellimm.2015.11.001","article-title":"Hunting down factor VIII in the immunopeptidome","volume":"301","author":"Hartholt","year":"2016","journal-title":"Cell Immunol"},{"key":"B62","doi-asserted-by":"publisher","first-page":"1429","DOI":"10.1182\/bloodadvances.2018030452","article-title":"Peptides identified on monocyte-derived dendritic cells: a marker for clinical immunogenicity to FVIII products","volume":"3","author":"Jankowski","year":"2019","journal-title":"Blood Adv"},{"key":"B63","doi-asserted-by":"publisher","first-page":"M110 002246","DOI":"10.1074\/mcp.M110.002246","article-title":"HLA-DR-presented peptide repertoires derived from human monocyte-derived dendritic cells pulsed with blood coagulation factor VIII","volume":"10","author":"Van Haren","year":"2011","journal-title":"Mol Cell Proteomics."},{"key":"B64","doi-asserted-by":"publisher","first-page":"e80239","DOI":"10.1371\/journal.pone.0080239","article-title":"Limited promiscuity of HLA-DRB1 presented peptides derived of blood coagulation factor VIII","volume":"8","author":"Van Haren","year":"2013","journal-title":"PLoS ONE"},{"key":"B65","doi-asserted-by":"publisher","first-page":"172","DOI":"10.3324\/haematol.2017.175083","article-title":"Comparative profiling of HLA-DR and HLA-DQ associated factor VIII peptides presented by monocyte-derived dendritic cells","volume":"103","author":"Peyron","year":"2018","journal-title":"Haematologica"},{"key":"B66","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1055\/s-0038-1655944","article-title":"HLA class II profile: a weak determinant of factor VIII inhibitor development in severe haemophilia A. UKHCDO Inhibitor Working Party","volume":"77","author":"Hay","year":"1997","journal-title":"Thromb Haemost"},{"key":"B67","doi-asserted-by":"publisher","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 of factor VIII","volume":"77","author":"Oldenburg","year":"1997","journal-title":"Thromb Haemost"},{"key":"B68","doi-asserted-by":"publisher","first-page":"2006","DOI":"10.1111\/j.1538-7836.2009.03636.x","article-title":"Impact of polymorphisms of the major histocompatibility complex class II, interleukin-10, tumor necrosis factor-alpha and cytotoxic T-lymphocyte antigen-4 genes on inhibitor development in severe hemophilia A","volume":"7","author":"Pavlova","year":"2009","journal-title":"J Thromb Haemost"},{"key":"B69","doi-asserted-by":"publisher","first-page":"895","DOI":"10.1182\/blood-2014-09-599365","article-title":"Factor VIII gene variants and inhibitor risk in African American hemophilia A patients","volume":"126","author":"Gunasekera","year":"2015","journal-title":"Blood"},{"key":"B70","doi-asserted-by":"publisher","first-page":"1382","DOI":"10.1161\/CIRCULATIONAHA.109.869156","article-title":"Novel associations of multiple genetic loci with plasma levels of factor VII, factor VIII, and von Willebrand factor: the CHARGE. (Cohorts for Heart and Aging Research in Genome Epidemiology) Consortium","volume":"121","author":"Smith","year":"2010","journal-title":"Circulation"},{"key":"B71","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1111\/jth.14322","article-title":"Exocytosis of Weibel-Palade bodies: how to unpack a vascular emergency kit","volume":"17","author":"Schillemans","year":"2019","journal-title":"J Thromb Haemost"},{"key":"B72","doi-asserted-by":"publisher","first-page":"4503","DOI":"10.1172\/JCI71245","article-title":"Syntaxin-binding protein STXBP5 inhibits endothelial exocytosis and promotes platelet secretion","volume":"124","author":"Zhu","year":"2014","journal-title":"J Clin Invest"},{"key":"B73","doi-asserted-by":"publisher","first-page":"5228","DOI":"10.1182\/blood-2012-10-457507","article-title":"The C-type lectin receptor CLEC4M binds, internalizes, and clears von Willebrand factor and contributes to the variation in plasma von Willebrand factor levels","volume":"121","author":"Rydz","year":"2013","journal-title":"Blood"},{"key":"B74","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1111\/jth.14404","article-title":"The endothelial lectin clearance receptor CLEC4M binds and internalizes factor VIII in a VWF-dependent and independent manner","volume":"17","author":"Swystun","year":"2019","journal-title":"J Thromb Haemost"},{"key":"B75","doi-asserted-by":"publisher","first-page":"3706","DOI":"10.1182\/blood-2014-02-555151","article-title":"A conditional knockout mouse model reveals endothelial cells as the principal and possibly exclusive source of plasma factor VIII","volume":"123","author":"Fahs","year":"2014","journal-title":"Blood"},{"key":"B76","doi-asserted-by":"publisher","first-page":"3697","DOI":"10.1182\/blood-2014-02-554501","article-title":"Murine coagulation factor VIII is synthesized in endothelial cells","volume":"123","author":"Everett","year":"2014","journal-title":"Blood"},{"key":"B77","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1002\/ajh.2830420408","article-title":"Loss of high-responder inhibitors in patients with severe hemophilia A and human immunodeficiency virus type 1 infection: a report from the Multi-Center Hemophilia Cohort Study","volume":"42","author":"Bray","year":"1993","journal-title":"Am J Hematol"},{"key":"B78","doi-asserted-by":"publisher","first-page":"1324","DOI":"10.1182\/blood.V95.4.1324.004k25_1324_1329","article-title":"Prevention and treatment of factor VIII inhibitors in murine hemophilia A","volume":"95","author":"Qian","year":"2000","journal-title":"Blood"},{"key":"B79","doi-asserted-by":"publisher","first-page":"2548","DOI":"10.1002\/1521-4141(200009)30:9<2548::AID-IMMU2548>3.0.CO;2-H","article-title":"Role of CD154 in the secondary immune response: the reduction of pre-existing splenic germinal centers and anti-factor VIII inhibitor titer","volume":"30","author":"Qian","year":"2000","journal-title":"Eur J Immunol."},{"key":"B80","doi-asserted-by":"publisher","first-page":"522","DOI":"10.1160\/TH03-12-0755","article-title":"Immunodominant T-cell epitopes in the factor VIII C2 domain are located within an inhibitory antibody binding site","volume":"92","author":"Pratt","year":"2004","journal-title":"Thromb Haemost"},{"key":"B81","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1182\/blood-2003-07-2456","article-title":"Preventing restimulation of memory B cells in hemophilia A: a potential new strategy for the treatment of antibody-dependent immune disorders","volume":"104","author":"Hausl","year":"2004","journal-title":"Blood"},{"key":"B82","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1055\/s-0037-1615873","article-title":"CD4+ T cell response to factor VIII in hemophilia A, acquired hemophilia, and healthy subjects","volume":"82","author":"Reding","year":"1999","journal-title":"Thromb Haemost"},{"key":"B83","doi-asserted-by":"publisher","first-page":"643","DOI":"10.1055\/s-0037-1614081","article-title":"Sensitization of CD4+ T cells to coagulation factor VIII: response in congenital and acquired hemophilia patients and in healthy subjects","volume":"84","author":"Reding","year":"2000","journal-title":"Thromb Haemost"},{"key":"B84","doi-asserted-by":"publisher","first-page":"1777","DOI":"10.1046\/j.1538-7836.2003.00251.x","article-title":"Human CD4+ T-cell epitope repertoire on the C2 domain of coagulation factor VIII","volume":"1","author":"Reding","year":"2003","journal-title":"J Thromb Haemost"},{"key":"B85","doi-asserted-by":"publisher","first-page":"1385","DOI":"10.1111\/j.1538-7836.2004.00850.x","article-title":"Epitope repertoire of human CD4+ T cells on the A3 domain of coagulation factor VIII","volume":"2","author":"Reding","year":"2004","journal-title":"J Thromb Haemost"},{"key":"B86","doi-asserted-by":"publisher","first-page":"1908","DOI":"10.1111\/j.1538-7836.2004.00918.x","article-title":"T cell recognition of the A2 domain of coagulation factor VIII in hemophilia patients and healthy subjects","volume":"2","author":"Hu","year":"2004","journal-title":"J Thromb Haemost"},{"key":"B87","doi-asserted-by":"publisher","first-page":"1351","DOI":"10.1182\/blood-2002-05-1369","article-title":"CD4+ T-cell clones specific for wild-type factor VIII: a molecular mechanism responsible for a higher incidence of inhibitor formation in mild\/moderate hemophilia A","volume":"101","author":"Jacquemin","year":"2003","journal-title":"Blood."},{"key":"B88","doi-asserted-by":"publisher","first-page":"2399","DOI":"10.1111\/j.1538-7836.2007.02762.x","article-title":"T-cell responses over time in a mild hemophilia A inhibitor subject: epitope identification and transient immunogenicity of the corresponding self-peptide","volume":"5","author":"James","year":"2007","journal-title":"J Thromb Haemost"},{"key":"B89","doi-asserted-by":"publisher","first-page":"1423","DOI":"10.1182\/blood-2009-01-200725","article-title":"Lineages of human T-cell clones, including T helper 17\/T helper 1 cells, isolated at different stages of anti-factor VIII immune responses","volume":"114","author":"Ettinger","year":"2009","journal-title":"Blood"},{"key":"B90","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1111\/j.1365-2516.2008.01905.x","article-title":"HLA-DR-restricted T-cell responses to factor VIII epitopes in a mild haemophilia A family with missense substitution A2201P","volume":"16","author":"Ettinger","year":"2010","journal-title":"Haemophilia"},{"key":"B91","doi-asserted-by":"publisher","first-page":"689","DOI":"10.1111\/j.1538-7836.2011.04202.x","article-title":"T-cell responses in two unrelated hemophilia A inhibitor subjects include an epitope at the factor VIII R593C missense site","volume":"9","author":"James","year":"2011","journal-title":"J Thromb Haemost"},{"key":"B92","doi-asserted-by":"publisher","first-page":"2043","DOI":"10.1182\/blood-2015-11-682468","article-title":"T cells from hemophilia A subjects recognize the same HLA-restricted FVIII epitope with a narrow TCR repertoire","volume":"128","author":"Ettinger","year":"2016","journal-title":"Blood"},{"key":"B93","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1111\/j.1538-7836.2007.02336.x","article-title":"Depletion of CD4+\/CD25high regulatory T cells may enhance or uncover factor VIII-specific T-cell responses in healthy individuals","volume":"5","author":"Kamate","year":"2007","journal-title":"J Thromb Haemost"},{"key":"B94","doi-asserted-by":"publisher","first-page":"2159","DOI":"10.1046\/j.1538-7836.2003.00366.x","article-title":"Recognition of coagulation factor VIII by CD4+ T cells of healthy humans","volume":"1","author":"Hu","year":"2003","journal-title":"J Thromb Haemost"},{"key":"B95","doi-asserted-by":"publisher","first-page":"788","DOI":"10.1160\/TH06-09-0519","article-title":"Cytokine production by CD4+ T cells specific for coagulation factor VIII in healthy subjects and haemophilia A patients","volume":"97","author":"Hu","year":"2007","journal-title":"Thromb Haemost"},{"key":"B96","doi-asserted-by":"publisher","first-page":"1842","DOI":"10.1182\/bloodadvances.2017008706","article-title":"CD4 T cells specific for factor VIII are present at high frequency in healthy donors and comprise naive and memory cells","volume":"1","author":"Meunier","year":"2017","journal-title":"Blood Adv"},{"key":"B97","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2019-124803","article-title":"Elispots and ex vivo expansion of FVIII-specific T-cell clones confirm specificity of CD4 + T-cell responses to self-FVIII in healthy non-hemophilic blood donors","volume":"134","author":"Karim","year":"2019","journal-title":"Blood"},{"key":"B98","doi-asserted-by":"publisher","first-page":"4741","DOI":"10.1182\/blood-2008-10-186452","article-title":"A role for thrombin in the initiation of the immune response to therapeutic factor VIII","volume":"114","author":"Skupsky","year":"2009","journal-title":"Blood"},{"key":"B99","doi-asserted-by":"publisher","first-page":"2512","DOI":"10.1182\/blood-2012-02-412361","article-title":"A major determinant of the immunogenicity of factor VIII in a murine model is independent of its procoagulant function","volume":"120","author":"Meeks","year":"2012","journal-title":"Blood"},{"key":"B100","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1186\/1756-8722-6-63","article-title":"High rate of spontaneous inhibitor clearance during the long term observation study of a single cohort of 524 haemophilia A patients not undergoing immunotolerance","volume":"6","author":"Tagariello","year":"2013","journal-title":"J Hematol Oncol"},{"key":"B101","doi-asserted-by":"publisher","first-page":"1999","DOI":"10.1182\/blood-2016-08-732123","article-title":"Monoepitopic anti-FVIII T-cell response","volume":"128","author":"Lacroix-Desmazes","year":"2016","journal-title":"Blood"},{"key":"B102","doi-asserted-by":"publisher","DOI":"10.1002\/rth2.12125","article-title":"Hemophilia A subjects with an intron-22 inversion mutation show robust T-cell responses to epitopes in both the FVIII heavy and light chain","volume":"93","author":"Gunasekera","year":"2018","journal-title":"Spec Compil Res Pract Thromb Haemost."},{"key":"B103","doi-asserted-by":"publisher","first-page":"468","DOI":"10.3389\/fimmu.2015.00468","article-title":"Lower affinity T cells are critical components and active participants of the immune response","volume":"6","author":"Martinez","year":"2015","journal-title":"Front Immunol"},{"key":"B104","doi-asserted-by":"publisher","first-page":"3494","DOI":"10.4049\/jimmunol.1600965","article-title":"Low antigen dose in adjuvant-based vaccination selectively induces CD4 T cells with enhanced functional avidity and protective efficacy","volume":"198","author":"Billeskov","year":"2017","journal-title":"J Immunol"},{"key":"B105","doi-asserted-by":"publisher","first-page":"2112","DOI":"10.1016\/j.celrep.2018.07.067","article-title":"Distinct graft-specific TCR avidity profiles during acute rejection and tolerance","volume":"24","author":"Miller","year":"2018","journal-title":"Cell Rep"},{"key":"B106","doi-asserted-by":"publisher","first-page":"4034","DOI":"10.1182\/blood-2009-06-228155","article-title":"CD4+FOXP3+ regulatory T cells confer long-term regulation of factor VIII-specific immune responses in plasmid-mediated gene therapy-treated hemophilia mice","volume":"114","author":"Miao","year":"2009","journal-title":"Blood"},{"key":"B107","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1038\/nri2138-c1","article-title":"Efficacy of regulatory T-cell immunotherapy: are inflammatory cytokines key determinants?","volume":"8","author":"Bayry","year":"2008","journal-title":"Nat Rev Immunol."},{"key":"B108","doi-asserted-by":"publisher","first-page":"262","DOI":"10.3389\/fimmu.2015.00262","article-title":"Complement system part i - molecular mechanisms of activation and regulation","volume":"6","author":"Merle","year":"2015","journal-title":"Front Immunol"},{"key":"B109","doi-asserted-by":"publisher","first-page":"257","DOI":"10.3389\/fimmu.2015.00257","article-title":"Complement system part ii: role in immunity","volume":"6","author":"Merle","year":"2015","journal-title":"Front Immunol"},{"key":"B110","doi-asserted-by":"publisher","first-page":"2370","DOI":"10.1016\/j.molimm.2007.11.003","article-title":"The tick-over theory revisited: formation and regulation of the soluble alternative complement C3 convertase. (C3(H2O)Bb)","volume":"45","author":"Bexborn","year":"2008","journal-title":"Mol Immunol."},{"key":"B111","doi-asserted-by":"publisher","first-page":"e0152337","DOI":"10.1371\/journal.pone.0152337","article-title":"Quantitative modeling of the alternative pathway of the complement system","volume":"11","author":"Zewde","year":"2016","journal-title":"PLoS ONE"},{"key":"B112","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1007\/s12026-013-8422-y","article-title":"Complement and autoimmunity","volume":"56","author":"Ballanti","year":"2013","journal-title":"Immunol Res"},{"key":"B113","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1016\/j.dci.2008.07.006","article-title":"Functional characterization of human C3\/cobra venom factor hybrid proteins for therapeutic complement depletion","volume":"33","author":"Fritzinger","year":"2009","journal-title":"Dev Comp Immunol"},{"key":"B114","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1055\/s-0038-1657777","article-title":"Inhibitor formation in congenital hemophilia A: an immunological perspective","volume":"44","author":"Delignat","year":"2018","journal-title":"Semin Thromb Hemost"},{"key":"B115","doi-asserted-by":"publisher","first-page":"1089","DOI":"10.1089\/ars.2007.2007","article-title":"Reactive oxygen species and endothelial activation","volume":"10","author":"Alom-Ruiz","year":"2008","journal-title":"Antioxid Redox Signal"},{"key":"B116","doi-asserted-by":"publisher","first-page":"897","DOI":"10.1023\/B:PHAM.0000029275.41323.a6","article-title":"Structure-immunogenicity relationships of therapeutic proteins","volume":"21","author":"Hermeling","year":"2004","journal-title":"Pharm Res"},{"key":"B117","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1189\/jlb.0209065","article-title":"Oxidative stress can alter the antigenicity of immunodominant peptides","volume":"87","author":"Weiskopf","year":"2010","journal-title":"J Leukoc Biol"},{"key":"B118","doi-asserted-by":"publisher","first-page":"27979","DOI":"10.1074\/jbc.M114.573402","article-title":"The cellular redox environment alters antigen presentation","volume":"289","author":"Trujillo","year":"2014","journal-title":"J Biol Chem"},{"key":"B119","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1016\/S0037-1963(01)90107-6","article-title":"B-domain deleted recombinant factor VIII formulation and stability","volume":"38","author":"Osterberg","year":"2001","journal-title":"Semin Hematol"},{"key":"B120","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1016\/S0049-3848(99)00211-X","article-title":"Singlet oxygen inactivates fibrinogen, factor V, factor VIII, factor X, and platelet aggregation of human blood","volume":"97","author":"Stief","year":"2000","journal-title":"Thromb Res"},{"key":"B121","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1016\/j.cellimm.2018.01.008","article-title":"Oxidation of factor VIII increases its immunogenicity in mice with severe hemophilia A","volume":"325","author":"Peyron","year":"2018","journal-title":"Cell Immunol"},{"key":"B122","doi-asserted-by":"publisher","first-page":"1062","DOI":"10.1111\/j.1538-7836.2012.04724.x","article-title":"Heme binds to factor VIII and inhibits its interaction with activated factor IX","volume":"10","author":"Repesse","year":"2012","journal-title":"J Thromb Haemost"},{"key":"B123","doi-asserted-by":"publisher","first-page":"2054","DOI":"10.1056\/NEJMoa1516437","article-title":"A randomized trial of factor VIII and neutralizing antibodies in hemophilia, A","volume":"374","author":"Peyvandi","year":"2016","journal-title":"N Engl J Med"},{"key":"B124","doi-asserted-by":"publisher","first-page":"3389","DOI":"10.1182\/blood-2014-07-580498","article-title":"Factor VIII brand and the incidence of factor VIII inhibitors in previously untreated UK children with severe hemophilia A, 2000-2011","volume":"124","author":"Collins","year":"2014","journal-title":"Blood"},{"key":"B125","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1056\/NEJMoa1208024","article-title":"Factor VIII products and inhibitor development in severe hemophilia A","volume":"368","author":"Gouw","year":"2013","journal-title":"N Engl J Med"},{"key":"B126","doi-asserted-by":"publisher","first-page":"3398","DOI":"10.1182\/blood-2014-07-586347","article-title":"Recombinant factor VIII products and inhibitor development in previously untreated boys with severe hemophilia A","volume":"124","author":"Calvez","year":"2014","journal-title":"Blood."},{"key":"B127","doi-asserted-by":"publisher","first-page":"179","DOI":"10.3324\/haematol.2017.174706","article-title":"Analyses of the FranceCoag cohort support differences in immunogenicity among one plasma-derived and two recombinant factor VIII brands in boys with severe hemophilia A","volume":"103","author":"Calvez","year":"2018","journal-title":"Haematologica."},{"key":"B128","doi-asserted-by":"publisher","first-page":"398","DOI":"10.1111\/hae.13747","article-title":"Recombinant factor VIII products and inhibitor development in previously untreated patients with severe haemophilia A: combined analysis of three studies","volume":"25","author":"Volkers","year":"2019","journal-title":"Haemophilia"},{"key":"B129","doi-asserted-by":"publisher","first-page":"1925","DOI":"10.3324\/haematol.2018.188219","article-title":"N-linked glycosylation modulates the immunogenicity of recombinant human factor VIII in hemophilia A mice","volume":"103","author":"Lai","year":"2018","journal-title":"Haematologica"},{"key":"B130","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1038\/nature18847","article-title":"The microbiome and innate immunity","volume":"535","author":"Thaiss","year":"2016","journal-title":"Nature"},{"key":"B131","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1038\/nature18848","article-title":"The microbiota in adaptive immune homeostasis and disease","volume":"535","author":"Honda","year":"2016","journal-title":"Nature"},{"key":"B132","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1038\/nri.2017.7","article-title":"Dysbiosis and the immune system","volume":"17","author":"Levy","year":"2017","journal-title":"Nat Rev Immunol"},{"key":"B133","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1111\/imm.12933","article-title":"Impacts of microbiome metabolites on immune regulation and autoimmunity","volume":"154","author":"Haase","year":"2018","journal-title":"Immunology"},{"key":"B134","doi-asserted-by":"publisher","first-page":"e00036","DOI":"10.1128\/MMBR.00036-17","article-title":"The first microbial colonizers of the human gut: composition, activities, and health implications of the infant gut microbiota","volume":"81","author":"Milani","year":"2017","journal-title":"Microbiol Mol Biol Rev"},{"key":"B135","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1002\/rth2.12227","article-title":"Dysbiotic gut microbiota diminishes short-chain fatty acid production and increases factor VIII immunogenicity in haemophilia A mice","volume":"3","author":"Cormier","year":"2019","journal-title":"Res Pract Thromb Haemost."},{"key":"B136","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/j.iac.2017.09.003","article-title":"Oral tolerance development and maintenance","volume":"38","author":"Wambre","year":"2018","journal-title":"Immunol Allergy Clin North Am"},{"key":"B137","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1084\/jem.142.2.312","article-title":"Termination of aquired and natural immunological tolerance with specific complexes","volume":"142","author":"Habicht","year":"1975","journal-title":"J Exp Med"},{"key":"B138","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1038\/newbio230180a0","article-title":"Induction of immunological tolerance by a hapten. (DNP) bound to a non-immunogenic protein carrier","volume":"230","author":"Borel","year":"1971","journal-title":"Nat New Biol"},{"key":"B139","doi-asserted-by":"publisher","first-page":"742","DOI":"10.1002\/eji.1830061016","article-title":"Effect of carrier-specific tolerance on the generation of helper cell function","volume":"6","author":"Sanfilippo","year":"1976","journal-title":"Eur J Immunol"},{"key":"B140","doi-asserted-by":"publisher","first-page":"5019","DOI":"10.1073\/pnas.93.10.5019","article-title":"Epitope-specific tolerance induction with an engineered immunoglobulin","volume":"93","author":"Zambidis","year":"1996","journal-title":"Proc Natl Acad Sci USA"},{"key":"B141","doi-asserted-by":"publisher","first-page":"1825","DOI":"10.1084\/jem.162.6.1825","article-title":"Crosslinking of surface immunoglobulin and Fc receptors on B lymphocytes inhibits stimulation of inositol phospholipid breakdown via the antigen receptors","volume":"162","author":"Bijsterbosch","year":"1985","journal-title":"J Exp Med"},{"key":"B142","doi-asserted-by":"crossref","first-page":"2204","DOI":"10.4049\/jimmunol.131.5.2204","article-title":"The use of haptenated immunoglobulins to induce B cell tolerance in vitro. The roles of hapten density and the Fc portion of the immunoglobulin carrier","volume":"131","author":"Waldschmidt","year":"1983","journal-title":"J Immunol"},{"key":"B143","doi-asserted-by":"publisher","first-page":"S9","DOI":"10.1007\/s10875-012-9768-y","article-title":"The immunologic functions of the neonatal Fc receptor for IgG","volume":"33","author":"Rath","year":"2013","journal-title":"J Clin Immunol"},{"key":"B144","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1016\/j.cellimm.2015.12.008","article-title":"Recombinant factor VIII Fc. (rFVIIIFc) fusion protein reduces immunogenicity and induces tolerance in hemophilia A mice","volume":"301","author":"Krishnamoorthy","year":"2016","journal-title":"Cell Immunol"},{"key":"B145","doi-asserted-by":"publisher","first-page":"922","DOI":"10.1002\/pbc.25874","article-title":"Reduction of factor VIII inhibitor titers during immune tolerance induction with recombinant factor VIII-Fc fusion protein","volume":"63","author":"Groomes","year":"2016","journal-title":"Pediatr Blood Cancer"},{"key":"B146","doi-asserted-by":"publisher","first-page":"e552","DOI":"10.1111\/hae.13064","article-title":"Extended half-life factor VIII for immune tolerance induction in haemophilia","volume":"22","author":"Malec","year":"2016","journal-title":"Haemophilia"},{"key":"B147","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1080\/17474086.2018.1419862","article-title":"A contemporary look at FVIII inhibitor development: still a great influence on the evolution of hemophilia therapies","volume":"11","author":"Santagostino","year":"2018","journal-title":"Expert Rev Hematol"},{"key":"B148","doi-asserted-by":"publisher","first-page":"2205","DOI":"10.1182\/blood-2017-12-822908","article-title":"Tolerogenic properties of the Fc portion of IgG and its relevance to the treatment and management of hemophilia","volume":"131","author":"Blumberg","year":"2018","journal-title":"Blood"},{"key":"B149","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1111\/hae.13413","article-title":"Recombinant factor VIII Fc fusion protein for immune tolerance induction in patients with severe haemophilia A with inhibitors-A retrospective analysis","volume":"24","author":"Carcao","year":"2018","journal-title":"Haemophilia"},{"key":"B150","doi-asserted-by":"publisher","first-page":"1527","DOI":"10.1002\/eji.1830260718","article-title":"An IgG-transporting Fc receptor expressed in the syncytiotrophoblast of human placenta","volume":"26","author":"Simister","year":"1996","journal-title":"Eur J Immunol"},{"key":"B151","doi-asserted-by":"publisher","first-page":"8375","DOI":"10.1073\/pnas.0803715105","article-title":"Infused Fc-tagged beta-glucuronidase crosses the placenta and produces clearance of storage in utero in mucopolysaccharidosis VII mice","volume":"105","author":"Grubb","year":"2008","journal-title":"Proc Natl Acad Sci USA"},{"key":"B152","doi-asserted-by":"publisher","first-page":"1562","DOI":"10.1126\/science.1164511","article-title":"Maternal alloantigens promote the development of tolerogenic fetal regulatory T cells in utero","volume":"322","author":"Mold","year":"2008","journal-title":"Science"},{"key":"B153","doi-asserted-by":"publisher","first-page":"275ra21","DOI":"10.1126\/scitranslmed.aaa1957","article-title":"Regulation of immune responses to protein therapeutics by transplacental induction of T cell tolerance","volume":"7","author":"Gupta","year":"2015","journal-title":"Sci Transl Med."},{"key":"B154","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1007\/s12016-009-8117-2","article-title":"A cellular viewpoint of anti-FVIII immune response in hemophilia A","volume":"37","author":"Andre","year":"2009","journal-title":"Clin Rev Allergy Immunol"},{"key":"B155","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1111\/jth.12993","article-title":"Factor VIII tolerance induction in haemophilia A mice via transplacental transfer of recombinant factor VIII Fc","volume":"13","author":"Georgescu","year":"2015","journal-title":"J Thromb Haemost."},{"key":"B156","doi-asserted-by":"publisher","first-page":"3532","DOI":"10.2337\/db15-0024","article-title":"Materno-Fetal transfer of preproinsulin through the neonatal Fc receptor prevents autoimmune Diabetes","volume":"64","author":"Culina","year":"2015","journal-title":"Diabetes"},{"key":"B157","doi-asserted-by":"publisher","first-page":"1773","DOI":"10.1056\/NEJM200106073442307","article-title":"The hemophilias\u2013from royal genes to gene therapy","volume":"344","author":"Mannucci","year":"2001","journal-title":"N Engl J Med"},{"key":"B158","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1056\/NEJMc0806809","article-title":"Elimination of antibodies to recombinant enzyme in Pompe's disease","volume":"360","author":"Mendelsohn","year":"2009","journal-title":"N Engl J Med"},{"key":"B159","first-page":"729","article-title":"Do small B cells induce tolerance?","volume":"23","author":"Eynon","year":"1991","journal-title":"Transplant Proc"},{"key":"B160","doi-asserted-by":"publisher","first-page":"991","DOI":"10.1146\/annurev.iy.12.040194.005015","article-title":"Tolerance, danger, and the extended family","volume":"12","author":"Matzinger","year":"1994","journal-title":"Annu Rev Immunol"},{"key":"B161","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1016\/j.cellimm.2005.06.007","article-title":"Tolerance induction via a B-cell delivered gene therapy-based protocol: optimization and role of the Ig scaffold","volume":"235","author":"Lei","year":"2005","journal-title":"Cell Immunol"},{"key":"B162","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1007\/BF03401674","article-title":"Genetically transferred central and peripheral immune tolerance via retroviral-mediated expression of immunogenic epitopes in hematopoietic progenitors or peripheral B lymphocytes","volume":"3","author":"Zambidis","year":"1997","journal-title":"Mol Med"},{"key":"B163","doi-asserted-by":"publisher","first-page":"780","DOI":"10.4049\/jimmunol.175.2.780","article-title":"Mechanisms of gene therapy for tolerance: B7 signaling is required for peptide-IgG gene-transferred tolerance induction","volume":"175","author":"Litzinger","year":"2005","journal-title":"J Immunol"},{"key":"B164","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/j.clim.2005.08.007","article-title":"B-cell delivered gene transfer of human S-Ag-Ig fusion protein protects from experimental autoimmune uveitis","volume":"118","author":"Liang","year":"2006","journal-title":"Clin Immunol"},{"key":"B165","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/j.cellimm.2006.06.004","article-title":"Treatment of diabetes in NOD mice by gene transfer of Ig-fusion proteins into B cells: role of T regulatory cells","volume":"240","author":"Soukhareva","year":"2006","journal-title":"Cell Immunol"},{"key":"B166","doi-asserted-by":"publisher","first-page":"1271","DOI":"10.1016\/j.bbmt.2013.06.004","article-title":"Adoptive transfer of umbilical cord blood-derived regulatory T cells and early viral reactivation","volume":"19","author":"Brunstein","year":"2013","journal-title":"Biol Blood Marrow Transplant"},{"key":"B167","doi-asserted-by":"publisher","DOI":"10.1111\/jth.14659","article-title":"Antigen-specific in vitro expansion of factor VIII-specific regulatory T cells induces tolerance in hemophilia A mice","author":"Smith","year":"2019","journal-title":"J Thromb Haemost."},{"key":"B168","doi-asserted-by":"publisher","first-page":"274","DOI":"10.3389\/fimmu.2019.00274","article-title":"Reprogrammed CD4+ T cells that express FoxP3+ control inhibitory antibody formation in hemophilia A mice","volume":"10","author":"Herzog","year":"2019","journal-title":"Front Immunol"},{"key":"B169","doi-asserted-by":"publisher","first-page":"1107","DOI":"10.1182\/blood-2014-04-566786","article-title":"Engineered antigen-specific human regulatory T cells: immunosuppression of FVIII-specific T- and B-cell responses","volume":"125","author":"Kim","year":"2015","journal-title":"Blood"},{"key":"B170","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1182\/blood-2016-07-727834","article-title":"FVIII-specific human chimeric antigen receptor T-regulatory cells suppress T- and B-cell responses to FVIII","volume":"129","author":"Yoon","year":"2017","journal-title":"Blood"},{"key":"B171","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/j.jaut.2018.05.003","article-title":"Engineered MBP-specific human Tregs ameliorate MOG-induced EAE through IL-2-triggered inhibition of effector T cells","volume":"92","author":"Kim","year":"2018","journal-title":"J Autoimmun"},{"key":"B172","doi-asserted-by":"publisher","first-page":"1434","DOI":"10.4049\/jimmunol.1701800","article-title":"Targeting antigen-specific B cells using antigen-expressing transduced regulatory T cells","volume":"201","author":"Zhang","year":"2018","journal-title":"J Immunol"},{"key":"B173","doi-asserted-by":"publisher","first-page":"2332","DOI":"10.1182\/bloodadvances.2018018556","article-title":"Engineered FVIII-expressing cytotoxic T cells target and kill FVIII-specific B cells in vitro and in vivo","volume":"2","author":"Parvathaneni","year":"2018","journal-title":"Blood Adv"},{"key":"B174","doi-asserted-by":"publisher","first-page":"1148","DOI":"10.1111\/pbi.12859","article-title":"Expression and assembly of largest foreign protein in chloroplasts: oral delivery of human FVIII made in lettuce chloroplasts robustly suppresses inhibitor formation in haemophilia A mice","volume":"16","author":"Kwon","year":"2018","journal-title":"Plant Biotechnol J"},{"key":"B175","doi-asserted-by":"publisher","first-page":"512","DOI":"10.1016\/j.ymthe.2016.11.009","article-title":"Oral tolerance induction in hemophilia B dogs fed with transplastomic lettuce","volume":"25","author":"Herzog","year":"2017","journal-title":"Mol Ther"},{"key":"B176","doi-asserted-by":"publisher","first-page":"1659","DOI":"10.1182\/blood-2013-10-528737","article-title":"Suppression of inhibitor formation against FVIII in a murine model of hemophilia A by oral delivery of antigens bioencapsulated in plant cells","volume":"124","author":"Sherman","year":"2014","journal-title":"Blood"},{"key":"B177","doi-asserted-by":"publisher","first-page":"E156","DOI":"10.1073\/pnas.1408686111","article-title":"Polymeric synthetic nanoparticles for the induction of antigen-specific immunological tolerance","volume":"112","author":"Maldonado","year":"2015","journal-title":"Proc Natl Acad Sci USA"},{"key":"B178","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1182\/blood-2018-08-872291","article-title":"New therapies for hemophilia","volume":"133","author":"Weyand","year":"2019","journal-title":"Blood"},{"key":"B179","doi-asserted-by":"publisher","first-page":"2044","DOI":"10.1056\/NEJMoa1511769","article-title":"Factor VIII-mimetic function of humanized bispecific antibody in hemophilia, A","volume":"374","author":"Shima","year":"2016","journal-title":"N Engl J Med"},{"key":"B180","doi-asserted-by":"publisher","first-page":"2463","DOI":"10.1182\/blood-2017-08-801662","article-title":"Emicizumab, a bispecific antibody recognizing coagulation factors IX and X: how does it actually compare to factor VIII?","volume":"130","author":"Lenting","year":"2017","journal-title":"Blood"},{"key":"B181","doi-asserted-by":"publisher","first-page":"1269","DOI":"10.1111\/jth.14556","article-title":"Emicizumab and thrombosis: the story so far","volume":"17","author":"Makris","year":"2019","journal-title":"J Thromb Haemost"},{"key":"B182","doi-asserted-by":"publisher","first-page":"813","DOI":"10.1126\/science.171.3973.813","article-title":"Kinetic differences in unresponsiveness of thymus and bone marrow cells","volume":"171","author":"Chiller","year":"1971","journal-title":"Science"},{"key":"B183","doi-asserted-by":"publisher","first-page":"eaan4672","DOI":"10.1126\/science.aan4672","article-title":"Gene therapy comes of age","volume":"359","author":"Dunbar","year":"2018","journal-title":"Science"},{"key":"B184","doi-asserted-by":"publisher","first-page":"5842","DOI":"10.1182\/blood-2010-06-288001","article-title":"Eradication of neutralizing antibodies to factor VIII in canine hemophilia A after liver gene therapy","volume":"116","author":"Finn","year":"2010","journal-title":"Blood"},{"key":"B185","doi-asserted-by":"publisher","first-page":"104","DOI":"10.2174\/156652309787909490","article-title":"Hepatic gene transfer as a means of tolerance induction to transgene products","volume":"9","author":"Loduca","year":"2009","journal-title":"Curr Gene Ther"},{"key":"B186","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1182\/blood-2016-05-718635","article-title":"Design and characterization of an APC-specific serpin for the treatment of hemophilia","volume":"129","author":"Polderdijk","year":"2017","journal-title":"Blood"},{"key":"B187","doi-asserted-by":"publisher","first-page":"446","DOI":"10.1097\/MOH.0000000000000364","article-title":"Targeting activated protein C to treat hemophilia","volume":"24","author":"Polderdijk","year":"2017","journal-title":"Curr Opin Hematol"},{"key":"B188","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1186\/s13073-018-0584-8","article-title":"Advanced model systems and tools for basic and translational human immunology","volume":"10","author":"Wagar","year":"2018","journal-title":"Genome Med"},{"key":"B189","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1002\/cyto.a.22799","article-title":"Multiparameter analysis of stimulated human peripheral blood mononuclear cells: a comparison of mass and fluorescence cytometry","volume":"89","author":"Nicholas","year":"2016","journal-title":"Cytometry A"},{"key":"B190","doi-asserted-by":"publisher","first-page":"20686","DOI":"10.1038\/srep20686","article-title":"Standardizing flow cytometry immunophenotyping analysis from the human immunophenotyping consortium","volume":"6","author":"Finak","year":"2016","journal-title":"Sci Rep"},{"key":"B191","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1016\/j.coi.2018.03.023","article-title":"Mass cytometry: a powerful tool for dissecting the immune landscape","volume":"51","author":"Simoni","year":"2018","journal-title":"Curr Opin Immunol"},{"key":"B192","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1007\/978-1-4939-2963-4_15","article-title":"Single-cell analysis of T-cell receptor \u03b1\u03b2 repertoire","volume":"1343","author":"Dash","year":"2015","journal-title":"Methods Mol Biol"},{"key":"B193","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jaut.2017.04.002","article-title":"Immune dysregulation in immunodeficiency disorders: the role of T-cell receptor sequencing","volume":"80","author":"Wong","year":"2017","journal-title":"J Autoimmun"},{"key":"B194","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1038\/nri3642","article-title":"Democratizing systems immunology with modular transcriptional repertoire analyses","volume":"14","author":"Chaussabel","year":"2014","journal-title":"Nat Rev Immunol"},{"key":"B195","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1126\/science.aan6828","article-title":"Single-cell transcriptomics to explore the immune system in health and disease","volume":"358","author":"Stubbington","year":"2017","journal-title":"Science"},{"key":"B196","doi-asserted-by":"publisher","first-page":"e280","DOI":"10.1111\/hae.12448","article-title":"Prospective observational cohort studies for studying rare diseases: the European PedNet Haemophilia Registry","volume":"20","author":"Fischer","year":"2014","journal-title":"Haemophilia"},{"key":"B197","doi-asserted-by":"publisher","first-page":"824","DOI":"10.1182\/bloodadvances.2016002923","article-title":"Novel approach to genetic analysis and results in 3000 hemophilia patients enrolled in the My Life, Our Future initiative","volume":"1","author":"Johnsen","year":"2017","journal-title":"Blood Adv"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fimmu.2019.02991\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,24]],"date-time":"2023-09-24T23:00:37Z","timestamp":1695596437000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fimmu.2019.02991\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1,10]]},"references-count":197,"alternative-id":["10.3389\/fimmu.2019.02991"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2019.02991","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,1,10]]},"article-number":"2991"}}