Cenit, Maria CarmenMartínez-Florensa, MarioConsuegra-Fernández, MartaBonet, LizetteCarnero Montoro, ElenaArmiger Borràs, NoeliaCaballero Baños, MiguelArias, Maria TeresaBenítez-Ribas, DanielOrtego Centeno, NorbertoRamón, Enrique deSabio, José MarioGarcía Hernández, Francisco JoséTolosa Vilella, CarlesSuárez, AnaGonzález-Gay, Miguel A.Bosch, ElenaMartín, JavierLozano Soto, Francisco2017-12-142017-12-142014-11-171932-6203https://hdl.handle.net/2445/118737OBJECTIVE: 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.9 p.application/pdfengcc-by (c) Cenit, Maria Carmen et al., 2014http://creativecommons.org/licenses/by/3.0/esLupus eritematósLimfòcitsImmunologiaLupus erythematosusLymphocytesImmunologyinfo:eu-repo/semantics/article6498442017-12-14info:eu-repo/semantics/openAccess25402503