Analysis of ancestral and functionally relevant CD5 variants in systemic lupus erythematosus patients

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  • dc.contributor.author Cenit, Maria Carmenca
  • dc.contributor.author Martínez-Florensa, Marioca
  • dc.contributor.author Consuegra, Martaca
  • dc.contributor.author Bonet, Lizetteca
  • dc.contributor.author Carnero-Montoro, Elena, 1985-ca
  • dc.contributor.author Armiger, Noeliaca
  • dc.contributor.author Caballero-Baños, Miguelca
  • dc.contributor.author Arias, Maria Teresaca
  • dc.contributor.author Benítez, Danielca
  • dc.contributor.author Ortego-Centeno, Norbertoca
  • dc.contributor.author Ramón, Enrique deca
  • dc.contributor.author Sabio, José Marioca
  • dc.contributor.author García-Hernández, Francisco J.ca
  • dc.contributor.author Tolosa, Carlesca
  • dc.contributor.author Suárez, Anaca
  • dc.contributor.author González-Gay, Miguelca
  • dc.contributor.author Bosch Fusté, Elenaca
  • dc.contributor.author Martín, Javierca
  • dc.contributor.author Lozano, Franciscoca
  • dc.date.accessioned 2015-05-25T09:06:59Z
  • dc.date.available 2015-05-25T09:06:59Z
  • dc.date.issued 2014ca
  • dc.description.abstract Objective: CD5 plays a crucial role in autoimmunity and is a well-established genetic risk factor of developing RA. Recently, evidence of positive selection has been provided for the CD5 Pro224-Val471 haplotype in East Asian populations. The aim of the present work was to further analyze the functional relevance of non-synonymous CD5 polymorphisms conforming the ancestral and the newly derived haplotypes (Pro224-Ala471 and Pro224-Val471, respectively) as well as to investigate the potential role of CD5 on the development of SLE and/or SLE nephritis. Methods: The CD5 SNPs rs2241002 (C/T; Pro224Leu) and rs2229177 (C/T; Ala471Val) were genotyped using TaqMan allelic discrimination assays in a total of 1,324 controls and 681 SLE patients of Spanish origin. In vitro analysis of CD3-mediated T cell proliferative and cytokine response profiles of healthy volunteers homozygous for the above mentioned CD5 haplotypes were also analyzed. Results: T-cell proliferation and cytokine release were significantly increased showing a bias towards to a Th2 profile after CD3 cross-linking of peripheral mononuclear cells from healthy individuals homozygous for the ancestral Pro224-Ala471 (CC) haplotype, compared to the more recently derived Pro224-Val471 (CT). The same allelic combination was statistically associated with Lupus nephritis./nConclusion: The ancestral Ala471 CD5 allele confers lymphocyte hyper-responsiveness to TCR/CD3 cross-linking and is associated with nephritis in SLE patients.en
  • dc.description.sponsorship This work was supported by grants from the Spanish Ministerio de Economía y Competitividad [SAF2010-19717 to FL, SAF2009-11110 to JM, SAF2011-29239, and BFU2008-01046 to EB], Generalitat de Catalunya [2009SGR00252 to FL, and 2009SGR1101 to EB], Junta de Andalucía [CTS-4977], and Instituto de Salud Carlos III and Fondo Europeo de Desarrollo Regional/FEDER [RD12/0009/0004 to JM]en
  • dc.format.mimetype application/pdfca
  • dc.identifier.citation Cenit MC, Martínez-Florensa M, Consuegra M, Bonet L, Carnero-Montoro E, Armiger N et al. Analysis of ancestral and functionally relevant CD5 variants in systemic lupus erythematosus patients. PLoS ONE. 2014;9(11):e113090. DOI: 10.1371/journal.pone.0113090ca
  • dc.identifier.doi http://dx.doi.org/10.1371/journal.pone.0113090
  • dc.identifier.issn 1932-6203ca
  • dc.identifier.uri http://hdl.handle.net/10230/23648
  • dc.language.iso engca
  • dc.publisher Public Library of Science (PLoS)ca
  • dc.relation.ispartof PLoS ONE. 2014;9(11):e113090
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/SAF2010-19717
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/SAF2009-11110
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/SAF2011-29239
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/BFU2008-01046
  • dc.rights © 2014 Cenit et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are crediteden
  • dc.rights.accessRights info:eu-repo/semantics/openAccessca
  • dc.subject.other Lupus eritematós sistèmicca
  • dc.title Analysis of ancestral and functionally relevant CD5 variants in systemic lupus erythematosus patientsen
  • dc.type info:eu-repo/semantics/articleca
  • dc.type.version info:eu-repo/semantics/publishedVersionca

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