RT Journal Article
T1 Analysis of ancestral and functionally relevant CD5 variants in systemic lupus erythematosus patients.
A1 Cenit, Maria Carmen
A1 Martínez-Florensa, Mario
A1 Consuegra, Marta
A1 Bonet, Lizette
A1 Carnero-Montoro, Elena
A1 Armiger, Noelia
A1 Caballero-Baños, Miguel
A1 Arias, Maria Teresa
A1 Benitez, Daniel
A1 Ortego-Centeno, Norberto
A1 de Ramón, Enrique
A1 Sabio, José Mario
A1 García-Hernández, Francisco J
A1 Tolosa, Carles
A1 Suárez, Ana
A1 González-Gay, Miguel A
A1 Bosch, Elena
A1 Martín, Javier
A1 Lozano, Francisco
K1 Antígenos CD5
K1 Autoinmunidad
K1 Estudios de casos y controles
K1 Predisposición genética a la enfermedad
K1 Genotipo
K1 Haplotipos
K1 Humanos
K1 Lupus eritematoso sistémico
K1 Nefritis lúpica
K1 Polimorfismo genético
K1 Alelos
AB 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.
PB Public Library of Science
YR 2014
FD 2014-11-17
LK http://hdl.handle.net/10668/2228
UL http://hdl.handle.net/10668/2228
LA en
NO 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
NO Comparative Study; Journal Article; Research Support, Non-U.S. Gov't;
DS RISalud
RD Apr 8, 2025