Key Genes of the Immune System and Predisposition to Acquired Hemophilia A: Evidence from a Spanish Cohort of 49 Patients Using Next-Generation Sequencing

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 predispos...

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Autores: Pardos Gea, Jose, Martin Fernandez, Laura, Closa, Laia, Ferrero, Ainara, Marzo, Cristina, Rubio Rivas, Manuel, Mitjavila Villeró, Francesca, González Porras, José Ramón, Bastida, José María, Mateo, José, Carrasco, Marina (Carrasco Pérez), Bernardo, Ángel, Astigarraga, Itziar, Aguinaco, Reyes, Corrales, Irene, Garcia Martínez, Iris, Vidal, Francisco
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/205347
Acceso en línea:https://hdl.handle.net/2445/205347
Access Level:acceso abierto
Palabra clave:Genètica mèdica
Hemofília
Medical genetics
Hemophilia
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spelling Key Genes of the Immune System and Predisposition to Acquired Hemophilia A: Evidence from a Spanish Cohort of 49 Patients Using Next-Generation SequencingPardos Gea, JoseMartin Fernandez, LauraClosa, LaiaFerrero, AinaraMarzo, CristinaRubio Rivas, ManuelMitjavila Villeró, FrancescaGonzález Porras, José RamónBastida, José MaríaMateo, JoséCarrasco, Marina (Carrasco Pérez)Bernardo, ÁngelAstigarraga, ItziarAguinaco, ReyesCorrales, IreneGarcia Martínez, IrisVidal, FranciscoGenètica mèdicaHemofíliaMedical geneticsHemophiliaAcquired 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' 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[0.06-0.85]) and DRB1*13:03 (p = 6.8 x 103, OR = 7.56[1.64-51.40]), 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.MDPI AG2024202420232024info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion14 p.application/pdfhttps://hdl.handle.net/2445/205347Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.3390/ijms242216372International Journal of Molecular Sciences, 2023, vol. 24, num. 22, p. 16372https://doi.org/10.3390/ijms242216372cc by (c) Pardos Gea, Jose et al., 2023http://creativecommons.org/licenses/by/3.0/es/info:eu-repo/semantics/openAccessoai:recercat.cat:2445/2053472026-05-29T05:05:01Z
dc.title.none.fl_str_mv Key Genes of the Immune System and Predisposition to Acquired Hemophilia A: Evidence from a Spanish Cohort of 49 Patients Using Next-Generation Sequencing
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
spellingShingle Key Genes of the Immune System and Predisposition to Acquired Hemophilia A: Evidence from a Spanish Cohort of 49 Patients Using Next-Generation Sequencing
Pardos Gea, Jose
Genètica mèdica
Hemofília
Medical genetics
Hemophilia
title_short Key Genes of the Immune System and Predisposition to Acquired Hemophilia A: Evidence from a Spanish Cohort of 49 Patients Using Next-Generation Sequencing
title_full Key Genes of the Immune System and Predisposition to Acquired Hemophilia A: Evidence from a Spanish Cohort of 49 Patients Using Next-Generation Sequencing
title_fullStr Key Genes of the Immune System and Predisposition to Acquired Hemophilia A: Evidence from a Spanish Cohort of 49 Patients Using Next-Generation Sequencing
title_full_unstemmed Key Genes of the Immune System and Predisposition to Acquired Hemophilia A: Evidence from a Spanish Cohort of 49 Patients Using Next-Generation Sequencing
title_sort Key Genes of the Immune System and Predisposition to Acquired Hemophilia A: Evidence from a Spanish Cohort of 49 Patients Using Next-Generation Sequencing
dc.creator.none.fl_str_mv Pardos Gea, Jose
Martin Fernandez, Laura
Closa, Laia
Ferrero, Ainara
Marzo, Cristina
Rubio Rivas, Manuel
Mitjavila Villeró, Francesca
González Porras, José Ramón
Bastida, José María
Mateo, José
Carrasco, Marina (Carrasco Pérez)
Bernardo, Ángel
Astigarraga, Itziar
Aguinaco, Reyes
Corrales, Irene
Garcia Martínez, Iris
Vidal, Francisco
author Pardos Gea, Jose
author_facet Pardos Gea, Jose
Martin Fernandez, Laura
Closa, Laia
Ferrero, Ainara
Marzo, Cristina
Rubio Rivas, Manuel
Mitjavila Villeró, Francesca
González Porras, José Ramón
Bastida, José María
Mateo, José
Carrasco, Marina (Carrasco Pérez)
Bernardo, Ángel
Astigarraga, Itziar
Aguinaco, Reyes
Corrales, Irene
Garcia Martínez, Iris
Vidal, Francisco
author_role author
author2 Martin Fernandez, Laura
Closa, Laia
Ferrero, Ainara
Marzo, Cristina
Rubio Rivas, Manuel
Mitjavila Villeró, Francesca
González Porras, José Ramón
Bastida, José María
Mateo, José
Carrasco, Marina (Carrasco Pérez)
Bernardo, Ángel
Astigarraga, Itziar
Aguinaco, Reyes
Corrales, Irene
Garcia Martínez, Iris
Vidal, Francisco
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Genètica mèdica
Hemofília
Medical genetics
Hemophilia
topic Genètica mèdica
Hemofília
Medical genetics
Hemophilia
description 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' 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[0.06-0.85]) and DRB1*13:03 (p = 6.8 x 103, OR = 7.56[1.64-51.40]), 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.
publishDate 2023
dc.date.none.fl_str_mv 2023
2024
2024
2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/205347
url https://hdl.handle.net/2445/205347
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.3390/ijms242216372
International Journal of Molecular Sciences, 2023, vol. 24, num. 22, p. 16372
https://doi.org/10.3390/ijms242216372
dc.rights.none.fl_str_mv cc by (c) Pardos Gea, Jose et al., 2023
http://creativecommons.org/licenses/by/3.0/es/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc by (c) Pardos Gea, Jose et al., 2023
http://creativecommons.org/licenses/by/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 14 p.
application/pdf
dc.publisher.none.fl_str_mv MDPI AG
publisher.none.fl_str_mv MDPI AG
dc.source.none.fl_str_mv Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,198674

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