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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. CONCLUSION: The ancestral Ala471 CD5 allele confers lymphocyte hyper-responsiveness to TCR/CD3 cross-linking and is associated with nephritis in SLE patients.
Fuente: PLoS One. 2014 Nov 17;9(11):e113090
Publisher: Public Library of Science
Publication date: 01/11/2014
No. of pages: 9
Publication type: Article
DOI: 10.1371/journal.pone.0113090
ISSN: 1932-6203
Spanish project: SAF2010-19717
Consult in UCrea Read publication
CENIT, MARIA CARMEN
MARTÍNEZ FLORENSA, MARIO
CONSUEGRA, MARTA
BONET, LIZETTE
CARNERO MONTORO, ELENA
ARMIGER, NOELIA
CABALLERO BAÑOS, MIGUEL
ARIAS, MARIA TERESA
BENITEZ, DANIEL
ORTEGO CENTENO, NORBERTO
RAMÓN GARRIDO, ENRIQUE DE
SABIO, JOSÉ MARIO
GARCÍA HERNÁNDEZ, FRANCISCO J.
TOLOSA, CARLES
SUÁREZ, ANA
MIGUEL ANGEL GONZALEZ-GAY MANTECON
BOSCH, ELENA
MARTÍN, JAVIER
LOZANO, FRANCISCO
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