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, J, Martin-Fernandez, L, Closa, L, Ferrero, A, Marzo, C, Rubio-Rivas, M, Mitjavila, F, González-Porras, JR, Bastida, JM, Mateo, J, Carrasco, M, Bernardo, A, Astigarraga, I, Aguinaco, R, Corrales, I, Garcia-Martínez, I, Vidal, F
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Institución:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
Repositorio:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
OAI Identifier:oai:iibsantpau.fundanetsuite.com:p17374
Acceso en línea:https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=17374
Access Level:acceso abierto
Palabra clave:rare bleeding disorders
Acquired hemophilia A
autoantibodies
next-generation sequencing
genetic predisposition to disease
immunogenetics
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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, JMartin-Fernandez, LClosa, LFerrero, AMarzo, CRubio-Rivas, MMitjavila, FGonzález-Porras, JRBastida, JMMateo, JCarrasco, MBernardo, AAstigarraga, IAguinaco, RCorrales, IGarcia-Martínez, IVidal, Frare bleeding disordersAcquired hemophilia Aautoantibodiesnext-generation sequencinggenetic predisposition to diseaseimmunogeneticsAcquired 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.MDPI2023info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=17374INTERNATIONAL JOURNAL OF MOLECULAR SCIENCESISSN: 16616596ISSNe: 14220067reponame:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pauinstname:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)Inglésinfo:eu-repo/semantics/openAccessoai:iibsantpau.fundanetsuite.com:p173742026-06-14T12:41:47Z
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, J
rare bleeding disorders
Acquired hemophilia A
autoantibodies
next-generation sequencing
genetic predisposition to disease
immunogenetics
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, J
Martin-Fernandez, L
Closa, L
Ferrero, A
Marzo, C
Rubio-Rivas, M
Mitjavila, F
González-Porras, JR
Bastida, JM
Mateo, J
Carrasco, M
Bernardo, A
Astigarraga, I
Aguinaco, R
Corrales, I
Garcia-Martínez, I
Vidal, F
author Pardos-Gea, J
author_facet Pardos-Gea, J
Martin-Fernandez, L
Closa, L
Ferrero, A
Marzo, C
Rubio-Rivas, M
Mitjavila, F
González-Porras, JR
Bastida, JM
Mateo, J
Carrasco, M
Bernardo, A
Astigarraga, I
Aguinaco, R
Corrales, I
Garcia-Martínez, I
Vidal, F
author_role author
author2 Martin-Fernandez, L
Closa, L
Ferrero, A
Marzo, C
Rubio-Rivas, M
Mitjavila, F
González-Porras, JR
Bastida, JM
Mateo, J
Carrasco, M
Bernardo, A
Astigarraga, I
Aguinaco, R
Corrales, I
Garcia-Martínez, I
Vidal, F
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv rare bleeding disorders
Acquired hemophilia A
autoantibodies
next-generation sequencing
genetic predisposition to disease
immunogenetics
topic rare bleeding disorders
Acquired hemophilia A
autoantibodies
next-generation sequencing
genetic predisposition to disease
immunogenetics
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
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://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=17374
url https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=17374
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
ISSN: 16616596
ISSNe: 14220067
reponame:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
instname:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
instname_str Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
reponame_str r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
collection r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812429

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