HLA- B*08 Identified as the Most Prominently Associated Major Histocompatibility Complex Locus for Anti-Carbamylated Protein Antibody-Positive/Anti-Cyclic Citrullinated Peptide-Negative Rheumatoid Arthritis.

González, Antonio; Regueiro, Cristina; Casares-Marfil, Desire; Lundberg, Karin; Knevel, Rachel; Acosta-Herrera, Marialbert; Rodriguez-Rodriguez, Luis; Lopez-Mejias, Raquel; Pérez Pampín, Eva; Triguero-Martinez, Ana; Nuño, Laura; Ferraz-Amaro, Ivan; Rodriguez-Carrio, Javier; Lopez-Pedrera, Rosario; Robustillo-Villarino, Montse; Castañeda, Santos; Remuzgo-Martinez, Sara; Alperi, Mercedes; Alegre-Sancho, Juan J; Balsa, Alejandro; Gonzalez-Alvaro, Isidoro; Mera Varela, Antonio; Fernandez-Gutierrez, Benjamin; Gonzalez-Gay, Miguel A; Trouw, Leendert A; Grönwall, Caroline; Padyukov, Leonid; Martin, Javier; González Martínez-Pedrayo, Antonio

HLA- B*08 Identified as the Most Prominently Associated Major Histocompatibility Complex Locus for Anti-Carbamylated Protein Antibody-Positive/Anti-Cyclic Citrullinated Peptide-Negative Rheumatoid Arthritis.

[EN] Objective: Previously, only the HLA-DRB1 alleles have been assessed in rheumatoid arthritis (RA). The aim of the present study was to identify the key major histocompatibility complex (MHC) susceptibility factors showing a significant association with anti-carbamylated protein antibody-positive...

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Autores:	González, Antonio, Regueiro, Cristina, Casares-Marfil, Desire, Lundberg, Karin, Knevel, Rachel, Acosta-Herrera, Marialbert, Rodriguez-Rodriguez, Luis, Lopez-Mejias, Raquel, Pérez Pampín, Eva, Triguero-Martinez, Ana, Nuño, Laura, Ferraz-Amaro, Ivan, Rodriguez-Carrio, Javier, Lopez-Pedrera, Rosario, Robustillo-Villarino, Montse, Castañeda, Santos, Remuzgo-Martinez, Sara, Alperi, Mercedes, Alegre-Sancho, Juan J, Balsa, Alejandro, Gonzalez-Alvaro, Isidoro, Mera Varela, Antonio, Fernandez-Gutierrez, Benjamin, Gonzalez-Gay, Miguel A, Trouw, Leendert A, Grönwall, Caroline, Padyukov, Leonid, Martin, Javier, González Martínez-Pedrayo, Antonio
Tipo de recurso:	artículo
Fecha de publicación:	2021
País:	España
Institución:	Servizo Galego de Saúde (SERGAS)
Repositorio:	RUNA. Repositorio da Consellería de Sanidade e Sergas
OAI Identifier:	oai:runa.sergas.gal:20.500.11940/17701
Acceso en línea:	https://pubmed.ncbi.nlm.nih.gov/33381897/ http://hdl.handle.net/20.500.11940/17701
Access Level:	acceso abierto
Palabra clave:	Anti-Citrullinated Protein Antibodies Arthritis, Rheumatoid Autoantibodies Rheumatology Arthritis Population Protein Carbamylation HLA-DRB1 Chains HLA-B8 Antigen Alleles autoanticuerpos antígeno HLA-B8 Carbamilación de Proteína alelos reumatología cadenas HLA-DRB1 artritis reumatoide artritis anti-carbamylated protein antibodies shared epitope IDIS CHUS

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oai_identifier_str	oai:runa.sergas.gal:20.500.11940/17701
network_acronym_str	ES
network_name_str	España
repository_id_str
spelling	HLA- B08 Identified as the Most Prominently Associated Major Histocompatibility Complex Locus for Anti-Carbamylated Protein Antibody-Positive/Anti-Cyclic Citrullinated Peptide-Negative Rheumatoid Arthritis.González, AntonioRegueiro, CristinaCasares-Marfil, DesireLundberg, KarinKnevel, RachelAcosta-Herrera, MarialbertRodriguez-Rodriguez, LuisLopez-Mejias, RaquelPérez Pampín, EvaTriguero-Martinez, AnaNuño, LauraFerraz-Amaro, IvanRodriguez-Carrio, JavierLopez-Pedrera, RosarioRobustillo-Villarino, MontseCastañeda, SantosRemuzgo-Martinez, SaraAlperi, MercedesAlegre-Sancho, Juan JBalsa, AlejandroGonzalez-Alvaro, IsidoroMera Varela, AntonioFernandez-Gutierrez, BenjaminGonzalez-Gay, Miguel ATrouw, Leendert AGrönwall, CarolinePadyukov, LeonidMartin, JavierGonzález Martínez-Pedrayo, AntonioAnti-Citrullinated Protein AntibodiesArthritis, RheumatoidAutoantibodiesRheumatologyArthritisPopulationProtein CarbamylationHLA-DRB1 ChainsHLA-B8 AntigenAllelesautoanticuerposantígeno HLA-B8Carbamilación de Proteínaalelosreumatologíacadenas HLA-DRB1artritis reumatoideartritisanti-carbamylated protein antibodiesshared epitopeIDISCHUS[EN] Objective: Previously, only the HLA-DRB1 alleles have been assessed in rheumatoid arthritis (RA). The aim of the present study was to identify the key major histocompatibility complex (MHC) susceptibility factors showing a significant association with anti-carbamylated protein antibody-positive (anti-CarP+) RA. Methods: Analyses were restricted to RA patients who were anti-cyclic citrullinated peptide antibody negative (anti-CCP-), because the anti-CCP status dominated the results otherwise. Therefore, we studied samples from 1,821 anti-CCP- RA patients and 6,821 population controls from Spain, Sweden, and the Netherlands. The genotypes for ~8,000 MHC biallelic variants were assessed by dense genotyping and imputation. Their association with the anti-CarP status in RA patients was tested with logistic regression and combined with inverse-variance meta-analysis. Significance of the associations was assessed according to a study-specific threshold of P < 2.0 × 10-5 . Results: The HLA-B08 allele and its correlated amino acid variant Asp-9 showed a significant association with anti-CarP+/anti-CCP- RA (P < 3.78 × 10-7 ; I2 = 0). This association was specific when assessed relative to 3 comparator groups: population controls, anti-CarP-/anti-CCP- RA patients, and anti-CCP- RA patients who were positive for other anti-citrullinated protein antibodies. Based on these findings, anti-CarP+/anti-CCP- RA patients could be separated from other antibody-defined subsets of RA patients in whom an association with the HLA-B08 allele has been previously demonstrated. No other MHC variant remained associated with anti-CarP+/anti-CCP- RA after accounting for the presence of the HLA-B08 allele. Specifically, the reported association of HLA-DRB103 was observed at a level comparable to that reported previously, but it was attributable to linkage disequilibrium. Conclusion: These results identify HLA-B08 carrying Asp-9 as the MHC locus showing the strongest association with anti-CarP+/anti-CCP- RA. This knowledge may help clarify the role of the HLA in susceptibility to specific subsets of RA, by shaping the spectrum of RA autoantibodies.Ministerio de Educación, Cultura y DeporteInnovative Medicines InitiativeInstituto de Salud Carlos III (ISCIII)2021info:eu-repo/semantics/articlehttps://pubmed.ncbi.nlm.nih.gov/33381897/http://hdl.handle.net/20.500.11940/17701reponame:RUNA. Repositorio da Consellería de Sanidade e Sergasinstname:Servizo Galego de Saúde (SERGAS)Inglésinfo:eu-repo/semantics/openAccessoai:runa.sergas.gal:20.500.11940/177012026-06-12T08:40:47Z
dc.title.none.fl_str_mv	HLA- B*08 Identified as the Most Prominently Associated Major Histocompatibility Complex Locus for Anti-Carbamylated Protein Antibody-Positive/Anti-Cyclic Citrullinated Peptide-Negative Rheumatoid Arthritis.
title	HLA- B*08 Identified as the Most Prominently Associated Major Histocompatibility Complex Locus for Anti-Carbamylated Protein Antibody-Positive/Anti-Cyclic Citrullinated Peptide-Negative Rheumatoid Arthritis.
spellingShingle	HLA- B*08 Identified as the Most Prominently Associated Major Histocompatibility Complex Locus for Anti-Carbamylated Protein Antibody-Positive/Anti-Cyclic Citrullinated Peptide-Negative Rheumatoid Arthritis. González, Antonio Anti-Citrullinated Protein Antibodies Arthritis, Rheumatoid Autoantibodies Rheumatology Arthritis Population Protein Carbamylation HLA-DRB1 Chains HLA-B8 Antigen Alleles autoanticuerpos antígeno HLA-B8 Carbamilación de Proteína alelos reumatología cadenas HLA-DRB1 artritis reumatoide artritis anti-carbamylated protein antibodies shared epitope IDIS CHUS
title_short	HLA- B*08 Identified as the Most Prominently Associated Major Histocompatibility Complex Locus for Anti-Carbamylated Protein Antibody-Positive/Anti-Cyclic Citrullinated Peptide-Negative Rheumatoid Arthritis.
title_full	HLA- B*08 Identified as the Most Prominently Associated Major Histocompatibility Complex Locus for Anti-Carbamylated Protein Antibody-Positive/Anti-Cyclic Citrullinated Peptide-Negative Rheumatoid Arthritis.
title_fullStr	HLA- B*08 Identified as the Most Prominently Associated Major Histocompatibility Complex Locus for Anti-Carbamylated Protein Antibody-Positive/Anti-Cyclic Citrullinated Peptide-Negative Rheumatoid Arthritis.
title_full_unstemmed	HLA- B*08 Identified as the Most Prominently Associated Major Histocompatibility Complex Locus for Anti-Carbamylated Protein Antibody-Positive/Anti-Cyclic Citrullinated Peptide-Negative Rheumatoid Arthritis.
title_sort	HLA- B*08 Identified as the Most Prominently Associated Major Histocompatibility Complex Locus for Anti-Carbamylated Protein Antibody-Positive/Anti-Cyclic Citrullinated Peptide-Negative Rheumatoid Arthritis.
dc.creator.none.fl_str_mv	González, Antonio Regueiro, Cristina Casares-Marfil, Desire Lundberg, Karin Knevel, Rachel Acosta-Herrera, Marialbert Rodriguez-Rodriguez, Luis Lopez-Mejias, Raquel Pérez Pampín, Eva Triguero-Martinez, Ana Nuño, Laura Ferraz-Amaro, Ivan Rodriguez-Carrio, Javier Lopez-Pedrera, Rosario Robustillo-Villarino, Montse Castañeda, Santos Remuzgo-Martinez, Sara Alperi, Mercedes Alegre-Sancho, Juan J Balsa, Alejandro Gonzalez-Alvaro, Isidoro Mera Varela, Antonio Fernandez-Gutierrez, Benjamin Gonzalez-Gay, Miguel A Trouw, Leendert A Grönwall, Caroline Padyukov, Leonid Martin, Javier González Martínez-Pedrayo, Antonio
author	González, Antonio
author_facet	González, Antonio Regueiro, Cristina Casares-Marfil, Desire Lundberg, Karin Knevel, Rachel Acosta-Herrera, Marialbert Rodriguez-Rodriguez, Luis Lopez-Mejias, Raquel Pérez Pampín, Eva Triguero-Martinez, Ana Nuño, Laura Ferraz-Amaro, Ivan Rodriguez-Carrio, Javier Lopez-Pedrera, Rosario Robustillo-Villarino, Montse Castañeda, Santos Remuzgo-Martinez, Sara Alperi, Mercedes Alegre-Sancho, Juan J Balsa, Alejandro Gonzalez-Alvaro, Isidoro Mera Varela, Antonio Fernandez-Gutierrez, Benjamin Gonzalez-Gay, Miguel A Trouw, Leendert A Grönwall, Caroline Padyukov, Leonid Martin, Javier González Martínez-Pedrayo, Antonio
author_role	author
author2	Regueiro, Cristina Casares-Marfil, Desire Lundberg, Karin Knevel, Rachel Acosta-Herrera, Marialbert Rodriguez-Rodriguez, Luis Lopez-Mejias, Raquel Pérez Pampín, Eva Triguero-Martinez, Ana Nuño, Laura Ferraz-Amaro, Ivan Rodriguez-Carrio, Javier Lopez-Pedrera, Rosario Robustillo-Villarino, Montse Castañeda, Santos Remuzgo-Martinez, Sara Alperi, Mercedes Alegre-Sancho, Juan J Balsa, Alejandro Gonzalez-Alvaro, Isidoro Mera Varela, Antonio Fernandez-Gutierrez, Benjamin Gonzalez-Gay, Miguel A Trouw, Leendert A Grönwall, Caroline Padyukov, Leonid Martin, Javier González Martínez-Pedrayo, Antonio
author2_role	author author author author author author author author author author author author author author author author author author author author author author author author author author author author
dc.subject.none.fl_str_mv	Anti-Citrullinated Protein Antibodies Arthritis, Rheumatoid Autoantibodies Rheumatology Arthritis Population Protein Carbamylation HLA-DRB1 Chains HLA-B8 Antigen Alleles autoanticuerpos antígeno HLA-B8 Carbamilación de Proteína alelos reumatología cadenas HLA-DRB1 artritis reumatoide artritis anti-carbamylated protein antibodies shared epitope IDIS CHUS
topic	Anti-Citrullinated Protein Antibodies Arthritis, Rheumatoid Autoantibodies Rheumatology Arthritis Population Protein Carbamylation HLA-DRB1 Chains HLA-B8 Antigen Alleles autoanticuerpos antígeno HLA-B8 Carbamilación de Proteína alelos reumatología cadenas HLA-DRB1 artritis reumatoide artritis anti-carbamylated protein antibodies shared epitope IDIS CHUS
description	[EN] Objective: Previously, only the HLA-DRB1 alleles have been assessed in rheumatoid arthritis (RA). The aim of the present study was to identify the key major histocompatibility complex (MHC) susceptibility factors showing a significant association with anti-carbamylated protein antibody-positive (anti-CarP+) RA. Methods: Analyses were restricted to RA patients who were anti-cyclic citrullinated peptide antibody negative (anti-CCP-), because the anti-CCP status dominated the results otherwise. Therefore, we studied samples from 1,821 anti-CCP- RA patients and 6,821 population controls from Spain, Sweden, and the Netherlands. The genotypes for ~8,000 MHC biallelic variants were assessed by dense genotyping and imputation. Their association with the anti-CarP status in RA patients was tested with logistic regression and combined with inverse-variance meta-analysis. Significance of the associations was assessed according to a study-specific threshold of P < 2.0 × 10-5 . Results: The HLA-B08 allele and its correlated amino acid variant Asp-9 showed a significant association with anti-CarP+/anti-CCP- RA (P < 3.78 × 10-7 ; I2 = 0). This association was specific when assessed relative to 3 comparator groups: population controls, anti-CarP-/anti-CCP- RA patients, and anti-CCP- RA patients who were positive for other anti-citrullinated protein antibodies. Based on these findings, anti-CarP+/anti-CCP- RA patients could be separated from other antibody-defined subsets of RA patients in whom an association with the HLA-B08 allele has been previously demonstrated. No other MHC variant remained associated with anti-CarP+/anti-CCP- RA after accounting for the presence of the HLA-B08 allele. Specifically, the reported association of HLA-DRB103 was observed at a level comparable to that reported previously, but it was attributable to linkage disequilibrium. Conclusion: These results identify HLA-B*08 carrying Asp-9 as the MHC locus showing the strongest association with anti-CarP+/anti-CCP- RA. This knowledge may help clarify the role of the HLA in susceptibility to specific subsets of RA, by shaping the spectrum of RA autoantibodies.
publishDate	2021
dc.date.none.fl_str_mv	2021
dc.type.none.fl_str_mv	info:eu-repo/semantics/article
format	article
dc.identifier.none.fl_str_mv	https://pubmed.ncbi.nlm.nih.gov/33381897/ http://hdl.handle.net/20.500.11940/17701
url	https://pubmed.ncbi.nlm.nih.gov/33381897/ http://hdl.handle.net/20.500.11940/17701
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.source.none.fl_str_mv	reponame:RUNA. Repositorio da Consellería de Sanidade e Sergas instname:Servizo Galego de Saúde (SERGAS)
instname_str	Servizo Galego de Saúde (SERGAS)
reponame_str	RUNA. Repositorio da Consellería de Sanidade e Sergas
collection	RUNA. Repositorio da Consellería de Sanidade e Sergas
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score	15,301603

HLA- B*08 Identified as the Most Prominently Associated Major Histocompatibility Complex Locus for Anti-Carbamylated Protein Antibody-Positive/Anti-Cyclic Citrullinated Peptide-Negative Rheumatoid Arthritis.

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