%0 Journal Article
%A Cenit, Maria Carmen
%A Martínez-Florensa, Mario
%A Consuegra, Marta
%A Bonet, Lizette
%A Carnero-Montoro, Elena
%A Armiger, Noelia
%A Caballero-Baños, Miguel
%A Arias, Maria Teresa
%A Benitez, Daniel
%A Ortego-Centeno, Norberto
%A de Ramón, Enrique
%A Sabio, José Mario
%A García-Hernández, Francisco J
%A Tolosa, Carles
%A Suárez, Ana
%A González-Gay, Miguel A
%A Bosch, Elena
%A Martín, Javier
%A Lozano, Francisco
%T Analysis of ancestral and functionally relevant CD5 variants in systemic lupus erythematosus patients.
%D 2014
%U http://hdl.handle.net/10668/2228
%X OBJECTIVECD5 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.METHODSThe 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.RESULTST-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.CONCLUSIONThe ancestral Ala471 CD5 allele confers lymphocyte hyper-responsiveness to TCR/CD3 cross-linking and is associated with nephritis in SLE patients.
%K Antígenos CD5
%K Autoinmunidad
%K Estudios de casos y controles
%K Predisposición genética a la enfermedad
%K Genotipo
%K Haplotipos
%K Humanos
%K Lupus eritematoso sistémico
%K Nefritis lúpica
%K Polimorfismo genético
%K Alelos
%~