{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T22:19:26Z","timestamp":1769638766281,"version":"3.49.0"},"reference-count":59,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2023,11,15]],"date-time":"2023-11-15T00:00:00Z","timestamp":1700006400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Spanish Ministry of Economy and Competitiveness (MINECO, Ministerio de Econom\u00eda y Competitividad)","award":["PI18\/01492"],"award-info":[{"award-number":["PI18\/01492"]}]},{"name":"Spanish Ministry of Economy and Competitiveness (MINECO, Ministerio de Econom\u00eda y Competitividad)","award":["IIR-ESP-002171"],"award-info":[{"award-number":["IIR-ESP-002171"]}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI18\/01492"],"award-info":[{"award-number":["PI18\/01492"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["IIR-ESP-002171"],"award-info":[{"award-number":["IIR-ESP-002171"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009431","name":"Baxalta US Inc.","doi-asserted-by":"publisher","award":["PI18\/01492"],"award-info":[{"award-number":["PI18\/01492"]}],"id":[{"id":"10.13039\/100009431","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009431","name":"Baxalta US Inc.","doi-asserted-by":"publisher","award":["IIR-ESP-002171"],"award-info":[{"award-number":["IIR-ESP-002171"]}],"id":[{"id":"10.13039\/100009431","id-type":"DOI","asserted-by":"publisher"}]},{"name":"European Regional Development Fund (ERDF)","award":["PI18\/01492"],"award-info":[{"award-number":["PI18\/01492"]}]},{"name":"European Regional Development Fund (ERDF)","award":["IIR-ESP-002171"],"award-info":[{"award-number":["IIR-ESP-002171"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Acquired hemophilia A (AHA) is a rare bleeding disorder caused by the presence of autoantibodies against factor VIII (FVIII). As with other autoimmune diseases, its etiology is complex and its genetic basis is unknown. The aim of this study was to identify the immunogenetic background that predisposes individuals to AHA. HLA and KIR gene clusters, as well as KLRK1, were sequenced using next-generation sequencing in 49 AHA patients. Associations between candidate genes involved in innate and adaptive immune responses and AHA were addressed by comparing the alleles, genotypes, haplotypes, and gene frequencies in the AHA cohort with those in the donors\u2019 samples or Spanish population cohort. Two genes of the HLA cluster, as well as rs1049174 in KLRK1, which tags the natural killer (NK) cytotoxic activity haplotype, were found to be linked to AHA. Specifically, A*03:01 (p = 0.024; odds ratio (OR) = 0.26[0.06\u20130.85]) and DRB1*13:03 (p = 6.8 \u00d7 103, OR = 7.56[1.64\u201351.40]), as well as rs1049174 (p = 0.012), were significantly associated with AHA. In addition, two AHA patients were found to carry one copy each of the low-frequency allele DQB1*03:09 (nallele = 2, 2.04%), which was completely absent in the donors. To the best of our knowledge, this is the first time that the involvement of these specific alleles in the predisposition to AHA has been proposed. Further molecular and functional studies will be needed to unravel their specific contributions. We believe our findings expand the current knowledge on the genetic factors involved in susceptibility to AHA, which will contribute to improving the diagnosis and prognosis of AHA patients.<\/jats:p>","DOI":"10.3390\/ijms242216372","type":"journal-article","created":{"date-parts":[[2023,11,15]],"date-time":"2023-11-15T10:51:37Z","timestamp":1700045497000},"page":"16372","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Key Genes of the Immune System and Predisposition to Acquired Hemophilia A: Evidence from a Spanish Cohort of 49 Patients Using Next-Generation Sequencing"],"prefix":"10.3390","volume":"24","author":[{"given":"Jose","family":"Pardos-Gea","sequence":"first","affiliation":[{"name":"Systemic Autoimmune Diseases Unit, Department of Internal Medicine, Vall d\u2019Hebron University Hospital, 08035 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8909-508X","authenticated-orcid":false,"given":"Laura","family":"Martin-Fernandez","sequence":"additional","affiliation":[{"name":"Congenital Coagulopathies Laboratory, Blood and Tissue Bank, 08005 Barcelona, Spain"},{"name":"Transfusional Medicine Group, Vall d\u2019Hebron Research Institute, Autonomous University of Barcelona (VHIR-UAB), 08035 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laia","family":"Closa","sequence":"additional","affiliation":[{"name":"Transfusional Medicine Group, Vall d\u2019Hebron Research Institute, Autonomous University of Barcelona (VHIR-UAB), 08035 Barcelona, Spain"},{"name":"Histocompatibility and Immunogenetics Laboratory, Blood and Tissue Bank, 08005 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ainara","family":"Ferrero","sequence":"additional","affiliation":[{"name":"Hematology Service, Arnau de Vilanova University Hospital, 25198 Lleida, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6085-2158","authenticated-orcid":false,"given":"Cristina","family":"Marzo","sequence":"additional","affiliation":[{"name":"Hematology Service, Arnau de Vilanova University Hospital, 25198 Lleida, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9548-1374","authenticated-orcid":false,"given":"Manuel","family":"Rubio-Rivas","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Bellvitge University Hospital, Bellvitge Biomedical Research Institute (IDIBELL), University of Barcelona, L\u2019Hospitalet de Llobregat, 08908 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Mitjavila","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Bellvitge University Hospital, Bellvitge Biomedical Research Institute (IDIBELL), University of Barcelona, L\u2019Hospitalet de Llobregat, 08908 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 Ram\u00f3n","family":"Gonz\u00e1lez-Porras","sequence":"additional","affiliation":[{"name":"Department of Hematology, Complejo Asistencial Universitario de Salamanca (CAUSA), Instituto de Investigaci\u00f3n Biomedica de Salamanca (IBSAL), Facultad de Medicina, Universidad de Salamanca (USAL), 37007 Salamanca, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8007-3909","authenticated-orcid":false,"given":"Jos\u00e9 Mar\u00eda","family":"Bastida","sequence":"additional","affiliation":[{"name":"Department of Hematology, Complejo Asistencial Universitario de Salamanca (CAUSA), Instituto de Investigaci\u00f3n Biomedica de Salamanca (IBSAL), Facultad de Medicina, Universidad de Salamanca (USAL), 37007 Salamanca, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9","family":"Mateo","sequence":"additional","affiliation":[{"name":"Thrombosis and Hemostasis Unit, Sant Pau Campus Salut Barcelona, 08025 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8301-8000","authenticated-orcid":false,"given":"Marina","family":"Carrasco","sequence":"additional","affiliation":[{"name":"Thrombosis and Hemostasis Unit, Sant Pau Campus Salut Barcelona, 08025 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9711-8037","authenticated-orcid":false,"given":"\u00c1ngel","family":"Bernardo","sequence":"additional","affiliation":[{"name":"Hematology Service, Central University Hospital of Asturias, 33011 Oviedo, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5012-0137","authenticated-orcid":false,"given":"Itziar","family":"Astigarraga","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Biobizkaia Health Research Institute, Hospital Universitario Cruces, University of the Basque Country UPV\/EHU, 48903 Barakaldo, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reyes","family":"Aguinaco","sequence":"additional","affiliation":[{"name":"Hematology Service, University Hospital Joan XXIII, 43002 Tarragona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irene","family":"Corrales","sequence":"additional","affiliation":[{"name":"Congenital Coagulopathies Laboratory, Blood and Tissue Bank, 08005 Barcelona, Spain"},{"name":"Transfusional Medicine Group, Vall d\u2019Hebron Research Institute, Autonomous University of Barcelona (VHIR-UAB), 08035 Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Cardiovasculares (CIBERCV), Instituto Carlos III (ISCIII), 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iris","family":"Garcia-Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Congenital Coagulopathies Laboratory, Blood and Tissue Bank, 08005 Barcelona, Spain"},{"name":"Transfusional Medicine Group, Vall d\u2019Hebron Research Institute, Autonomous University of Barcelona (VHIR-UAB), 08035 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francisco","family":"Vidal","sequence":"additional","affiliation":[{"name":"Congenital Coagulopathies Laboratory, Blood and Tissue Bank, 08005 Barcelona, Spain"},{"name":"Transfusional Medicine Group, Vall d\u2019Hebron Research Institute, Autonomous University of Barcelona (VHIR-UAB), 08035 Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Cardiovasculares (CIBERCV), Instituto Carlos III (ISCIII), 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1002\/ajh.24777","article-title":"Acquired Hemophilia A: Updated Review of Evidence and Treatment Guidance","volume":"92","author":"Kempton","year":"2017","journal-title":"Am. J. Hematol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1002\/ajh.20390","article-title":"Acquired Hemophilia A: A Concise Review","volume":"80","author":"Franchini","year":"2005","journal-title":"Am. J. Hematol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1870","DOI":"10.1182\/blood-2006-06-029850","article-title":"Acquired Hemophilia A in the United Kingdom: A 2-Year National Surveillance Study by the United Kingdom Haemophilia Centre Doctors\u2019 Organisation","volume":"109","author":"Collins","year":"2007","journal-title":"Blood"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1055\/s-0029-1245109","article-title":"Twelve Years of Experience of Acquired Hemophilia A: Trials and Tribulations in South Australia","volume":"35","author":"Tay","year":"2009","journal-title":"Semin. Thromb. Hemost."},{"key":"ref_5","first-page":"e163","article-title":"Diagnostic Delay in Acquired Haemophilia: Analysis of Causes and Consequences in a 20-Year Spanish Cohort","volume":"24","author":"Parra","year":"2018","journal-title":"Haemophilia"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1791","DOI":"10.3324\/haematol.2019.230771","article-title":"International Recommendations on the Diagnosis and Treatment of Acquired Hemophilia A","volume":"105","author":"Tiede","year":"2020","journal-title":"Haematologica"},{"key":"ref_7","doi-asserted-by":"crossref","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":"ref_8","doi-asserted-by":"crossref","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":"ref_9","doi-asserted-by":"crossref","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":"ref_10","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1111\/j.1365-2516.2007.01618.x","article-title":"Increased Frequency of the CTLA-4 49 A\/G Polymorphism in Patients with Acquired Haemophilia A Compared to Healthy Controls","volume":"14","author":"Pavlova","year":"2008","journal-title":"Haemophilia"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1007\/s00277-009-0887-3","article-title":"Acquired Haemophilia Caused by Non-Haemophilic Factor VIII Gene Variants","volume":"89","author":"Tiede","year":"2010","journal-title":"Ann. Hematol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"49","DOI":"10.5045\/kjh.2011.46.1.49","article-title":"Identification of a Shared F8 Mutation in the Korean Patients with Acquired Hemophilia A","volume":"46","author":"Hwang","year":"2011","journal-title":"Korean J. Hematol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1111\/j.1365-2516.2008.01976.x","article-title":"HLA Genotype in Patients with Acquired Haemophilia A","volume":"16","author":"Pavlova","year":"2010","journal-title":"Haemophilia"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1111\/j.1365-2567.2010.03360.x","article-title":"Natural Killer Cells in Human Autoimmune Diseases","volume":"131","author":"Schleinitz","year":"2010","journal-title":"Immunology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1111\/j.1365-2567.2009.03045.x","article-title":"Natural Killer Cells: Integrating Diversity with Function","volume":"126","author":"Cheent","year":"2009","journal-title":"Immunology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.molimm.2009.02.023","article-title":"The Role of the Activating Receptor NKG2D in Autoimmunity","volume":"47","year":"2009","journal-title":"Mol. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1158\/0008-5472.CAN-05-2776","article-title":"Identification of the NKG2D Haplotypes Associated with Natural Cytotoxic Activity of Peripheral Blood Lymphocytes and Cancer Immunosurveillance","volume":"66","author":"Hayashi","year":"2006","journal-title":"Cancer Res."},{"key":"ref_18","first-page":"D783","article-title":"Allele Frequency Net Database (AFND) 2020 Update: Gold-Standard Data Classification, Open Access Genotype Data and New Query Tools","volume":"48","author":"McCabe","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"The 1000 Genomes Project Consortium (2015). A Global Reference for Human Genetic Variation. Nature, 526, 68\u201374.","DOI":"10.1038\/nature15393"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1002\/ajh.26009","article-title":"Treatment of Acquired Hemophilia A, a Balancing Act: Results from a 27-Year Dutch Cohort Study","volume":"96","author":"Schep","year":"2021","journal-title":"Am. J. Hematol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1182\/blood-2014-07-587089","article-title":"Prognostic Factors for Remission of and Survival in Acquired Hemophilia A (AHA): Results from the GTH-AH 01\/2010 Study","volume":"125","author":"Tiede","year":"2015","journal-title":"Blood"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1097\/MBC.0000000000000582","article-title":"Assessment of Acquired Hemophilia Patient Demographics in the United States: The Hemostasis and Thrombosis Research Society Registry","volume":"27","author":"Kessler","year":"2016","journal-title":"Blood Coagul. Fibrinolysis"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1111\/j.1538-7836.2012.04654.x","article-title":"Demographic and Clinical Data in Acquired Hemophilia A: Results from the European Acquired Haemophilia Registry (EACH2)","volume":"10","author":"Knoebl","year":"2012","journal-title":"J. Thromb. Haemost."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1111\/hae.12138","article-title":"Outcome of Acquired Haemophilia in France: The Prospective SACHA (Surveillance Des Auto AntiCorps Au Cours de l\u2019H\u00e9mophilie Acquise) Registry","volume":"19","author":"Borg","year":"2013","journal-title":"Haemophilia"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e244","DOI":"10.1111\/hae.14054","article-title":"Predictors of Response and Outcome of Patients with Acquired Haemophilia A","volume":"26","author":"Onwubiko","year":"2020","journal-title":"Haemophilia"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e383","DOI":"10.1111\/hae.13598","article-title":"Retrospective Review of Acquired Haemophilia A from the Largest Canadian Haemophilia Treatment Centre","volume":"24","author":"Jayakar","year":"2018","journal-title":"Haemophilia"},{"key":"ref_27","unstructured":"Anaya, J.M., Shoenfeld, Y., Rojas-Villarraga, A., Levy, R.A., and Cervera, R. (2013). Autoimmunity: From Bench to Bedside, El Rosario University Press."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1038\/s41581-023-00720-1","article-title":"Pathogenesis of Autoimmune Disease","volume":"19","author":"Pisetsky","year":"2023","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1038\/nri.2017.143","article-title":"HLA Variation and Disease","volume":"18","author":"Dendrou","year":"2018","journal-title":"Nat. Rev. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","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":"Meslier","year":"2009","journal-title":"Clin. Rev. Allergy Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1111\/j.1365-2516.2010.02259.x","article-title":"Genetic Markers in Acquired Haemophilia","volume":"16","author":"Oldenburg","year":"2010","journal-title":"Haemophilia"},{"key":"ref_32","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 of Factor VIII","volume":"77","author":"Oldenburg","year":"1997","journal-title":"Thromb. Haemost."},{"key":"ref_33","doi-asserted-by":"crossref","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-\u03b1 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":"ref_34","doi-asserted-by":"crossref","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","volume":"77","author":"Hay","year":"1997","journal-title":"Thromb. Haemost."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.ejcb.2011.03.003","article-title":"HLA Class I-Associated Diseases with a Suspected Autoimmune Etiology: HLA-B27 Subtypes as a Model System","volume":"91","author":"Loll","year":"2012","journal-title":"Eur. J. Cell Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1111\/j.1600-065X.1999.tb01399.x","article-title":"Genomics of the Major Histocompatibility Complex: Haplotypes, Duplication, Retroviruses and Disease","volume":"167","author":"Dawkins","year":"1999","journal-title":"Immunol. Rev."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.jaut.2015.06.010","article-title":"The Immunogenetics of Multiple Sclerosis: A Comprehensive Review","volume":"64","author":"Hollenbach","year":"2015","journal-title":"J. Autoimmun."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"948723","DOI":"10.1155\/2015\/948723","article-title":"The Protective Role of HLA-DRB1(\u2217)13 in Autoimmune Diseases","volume":"2015","author":"Bettencourt","year":"2015","journal-title":"J. Immunol. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"S26","DOI":"10.1055\/s-0037-1617113","article-title":"Inhibitor-Immunology-Study. Different HLA-Types Seem to Be Involved in the Inhibitor Development in Haemophilia A","volume":"28","author":"Wieland","year":"2008","journal-title":"Hamostaseologie"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2637","DOI":"10.1002\/art.21272","article-title":"An Independent Role of Protective HLA Class II Alleles in Rheumatoid Arthritis Severity and Susceptibility","volume":"52","author":"Huizinga","year":"2005","journal-title":"Arthritis Rheum."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/s13317-019-0124-6","article-title":"Associations between HLA and Autoimmune Neurological Diseases with Autoantibodies","volume":"11","author":"Vogrig","year":"2020","journal-title":"Autoimmun. Highlights"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1172\/JCI74961","article-title":"Cell-Surface MHC Density Profiling Reveals Instability of Autoimmunity-Associated HLA","volume":"125","author":"Miyadera","year":"2015","journal-title":"J. Clin. Investig."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"e5118","DOI":"10.7717\/peerj.5118","article-title":"Peptide Presentation by HLA-DQ Molecules Is Associated with the Development of Immune Tolerance","volume":"6","author":"Manczinger","year":"2018","journal-title":"PeerJ"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1093\/rheumatology\/39.10.1060","article-title":"HLA Association with Autoimmune Disease: A Failure to Protect?","volume":"39","author":"Zanelli","year":"2000","journal-title":"Rheumatology"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.1093\/ndt\/gfn450","article-title":"The Association of Anti-r-HuEpo-Associated Pure Red Cell Aplasia with HLA-DRB1*09-DQB1*0309","volume":"24","author":"Praditpornsilpa","year":"2009","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"622306","DOI":"10.3389\/fimmu.2021.622306","article-title":"The Role of Natural Killer Cells in Autoimmune Diseases","volume":"12","author":"Kucuksezer","year":"2012","journal-title":"Front. Immunol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"624687","DOI":"10.3389\/fimmu.2021.624687","article-title":"NK Cells in Autoimmune Diseases: Protective or Pathogenic?","volume":"12","author":"Liu","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1665","DOI":"10.3389\/fimmu.2018.01665","article-title":"Natural Killer Cells Exhibit a Peculiar Phenotypic Profile in Systemic Sclerosis and Are Potent Inducers of Endothelial Microparticles Release","volume":"9","author":"Benyamine","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2063","DOI":"10.1111\/j.1538-7836.2010.03975.x","article-title":"ISTH\/SSC Bleeding Assessment Tool: A Standardized Questionnaire and a Proposal for a New Bleeding Score for Inherited Bleeding Disorders","volume":"8","author":"Rodeghiero","year":"2010","journal-title":"J. Thromb. Haemost."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"3821","DOI":"10.1182\/bloodadvances.2021004626","article-title":"Management of Acquired Hemophilia A: Results from the Spanish Registry","volume":"5","author":"Haya","year":"2021","journal-title":"Blood Adv."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2991","DOI":"10.3389\/fimmu.2018.02991","article-title":"Design and Validation of a Multiplex KIR and HLA Class I Genotyping Method Using Next Generation Sequencing","volume":"9","author":"Closa","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1111\/tan.13754","article-title":"Distribution of Human Killer Cell Immunoglobulin-like Receptors and Ligands among Blood Donors of Catalonia","volume":"95","author":"Closa","year":"2020","journal-title":"HLA"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1111\/tan.13644","article-title":"HLA-A, -B, -C, -DRB1, and -DQB1 Allele and Haplotype Frequencies: An Analysis of Umbilical Cord Blood Units at the Barcelona Cord Blood Bank","volume":"94","author":"Enrich","year":"2019","journal-title":"HLA"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1111\/tan.14221","article-title":"High-Throughput Genotyping of HLA-G, HLA-F, MICA, and MICB and Analysis of Frequency Distributions in Healthy Blood Donors from Catalonia","volume":"97","author":"Closa","year":"2021","journal-title":"HLA"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1111\/tan.14515","article-title":"Natural Killer Cell Receptors and Ligand Variants Modulate Response to Tyrosine Kinase Inhibitors in Patients with Chronic Myeloid Leukemia","volume":"99","author":"Closa","year":"2022","journal-title":"HLA"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"39231","DOI":"10.1038\/srep39231","article-title":"A Functional Polymorphism in the NKG2D Gene Modulates NK-Cell Cytotoxicity and Is Associated with Susceptibility to Human Papilloma Virus-Related Cancers","volume":"6","author":"Espinoza","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1093\/biostatistics\/kxp050","article-title":"Confidence Intervals That Match Fisher\u2019s Exact or Blaker\u2019s Exact Tests","volume":"11","author":"Fay","year":"2010","journal-title":"Biostatistics"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1046\/j.1365-2141.2003.04162.x","article-title":"Acquired haemophilia: Review and meta-analysis focused on therapy and prognostic factors","volume":"121","author":"Delgado","year":"2003","journal-title":"Br. J. Haematol."},{"key":"ref_59","first-page":"200","article-title":"A survey of 215 non-hemophilic patients with inhibitors to Factor VIII","volume":"30","author":"Green","year":"1981","journal-title":"Thromb. Haemost."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/22\/16372\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:23:38Z","timestamp":1760131418000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/22\/16372"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,15]]},"references-count":59,"journal-issue":{"issue":"22","published-online":{"date-parts":[[2023,11]]}},"alternative-id":["ijms242216372"],"URL":"https:\/\/doi.org\/10.3390\/ijms242216372","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,15]]}}}