Cenit, Maria CarmenMartínez-Florensa, MarioConsuegra, MartaBonet, LizetteCarnero-Montoro, Elena, 1985-Armiger, NoeliaCaballero-Baños, MiguelArias, Maria TeresaBenítez, DanielOrtego-Centeno, NorbertoRamón, Enrique deSabio, José MarioGarcía-Hernández, Francisco J.Tolosa, CarlesSuárez, AnaGonzález-Gay, MiguelBosch Fusté, ElenaMartín, JavierLozano, Francisco2015-05-252015-05-252014Cenit 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.01130901932-6203http://hdl.handle.net/10230/23648Objective: 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.application/pdfeng© 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 creditedLupus eritematós sistèmicinfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1371/journal.pone.0113090info:eu-repo/semantics/openAccess