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de la Concha E.G.,Institute Investigacion Sanitaria San Carlos IdISSC | Cavanillas M.L.,Institute Investigacion Sanitaria San Carlos IdISSC | Cenit M.C.,Institute Investigacion Sanitaria San Carlos IdISSC | Urcelay E.,Institute Investigacion Sanitaria San Carlos IdISSC | And 6 more authors.
PLoS ONE | Year: 2012

Background: Multiple sclerosis (MS) is a multifactorial disease with a genetic basis. The strongest associations with the disease lie in the Human Leukocyte Antigen (HLA) region. However, except for the DRB1*15:01 allele, the main risk factor associated to MS so far, no consistent effect has been described for any other variant. One example is HLA-DRB1*03:01, with a heterogeneous effect across populations and studies. We postulate that those discrepancies could be due to differences in the diverse haplotypes bearing that allele. Thus, we aimed at studying the association of DRB1*03:01 with MS susceptibility considering this allele globally and stratified by haplotypes. We also evaluated the association with the presence of oligoclonal IgM bands against myelin lipids (OCMB) in cerebrospinal fluid. Methods: Genotyping of HLA-B, -DRB1 and -DQA1 was performed in 1068 MS patients and 624 ethnically matched healthy controls. One hundred and thirty-nine MS patients were classified according to the presence (M+, 58 patients)/absence (M-, 81 patients) of OCMB. Comparisons between groups (MS patients vs. controls and M+ vs. M-) were performed with the chi-square test or the Fisher exact test. Results: Association of DRB1*03:01 with MS susceptibility was observed but with different haplotypic contribution, being the ancestral haplotype (AH) 18.2 the one causing the highest risk. Comparisons between M+, M- and controls showed that the AH 18.2 was affecting only M+ individuals, conferring a risk similar to that caused by DRB1*15:01. Conclusions: The diverse DRB1*03:01-containing haplotypes contribute with different risk to MS susceptibility. The AH 18.2 causes the highest risk and affects only to individuals showing OCMB. © 2012 de la Concha et al. Source


Lopez-Gomez C.,Hospital Regional Universitario Carlos Haya and Fundacion | Fernandez O.,Hospital Regional Universitario Carlos Haya and Fundacion | Garcia-Leon J.A.,Hospital Regional Universitario Carlos Haya and Fundacion | Pinto-Medel M.J.,Hospital Regional Universitario Carlos Haya and Fundacion | And 13 more authors.
PLoS ONE | Year: 2011

The TNF-related apoptosis inducing ligand (TRAIL)/TRAIL receptor system participates in crucial steps in immune cell activation or differentiation. It is able to inhibit proliferation and activation of T cells and to induce apoptosis of neurons and oligodendrocytes, and seems to be implicated in autoimmune diseases. Thus, TRAIL and TRAIL receptor genes are potential candidates for involvement in susceptibility to multiple sclerosis (MS). To test whether single-nucleotide polymorphisms (SNPs) in the human genes encoding TRAIL, TRAILR-1, TRAILR-2, TRAILR-3 and TRAILR-4 are associated with MS susceptibility, we performed a candidate gene case-control study in the Spanish population. 59 SNPs in the TRAIL and TRAIL receptor genes were analysed in 628 MS patients and 660 controls, and validated in an additional cohort of 295 MS patients and 233 controls. Despite none of the SNPs withstood the highly conservative Bonferroni correction, three SNPs showing uncorrected p values<0.05 were successfully replicated: rs4894559 in TRAIL gene, p = 9.8×10 -4, OR = 1.34; rs4872077, in TRAILR-1 gene, p = 0.005, OR = 1.72; and rs1001793 in TRAILR-2 gene, p = 0.012, OR = 0.84. The combination of the alleles G/T/A in these SNPs appears to be associated with a reduced risk of developing MS (p = 2.12×10 -5, OR = 0.59). These results suggest that genes of the TRAIL/TRAIL receptor system exerts a genetic influence on MS. © 2011 López-Gómez et al. Source


Pinto-Medel M.J.,Hospital Regional Universitario Carlos Haya and Fundacion | Garcia-Leon J.A.,Hospital Regional Universitario Carlos Haya and Fundacion | Oliver-Martos B.,Hospital Regional Universitario Carlos Haya and Fundacion | Lopez-Gomez C.,Hospital Regional Universitario Carlos Haya and Fundacion | And 6 more authors.
Journal of Neuroimmunology | Year: 2012

Multiple sclerosis (MS) is a chronic debilitating disease, in which T-cells are considered to play a pivotal role. CD28 is the quintessential costimulatory molecule on T-cells and its expression declines progressively with repeated stimulations, leading to the generation of CD28 - T-cells. Our aim was to examine whether CD4 +CD28 - T-cells were enriched in MS patients, and characterize the phenotype of this subset in MS patients and healthy controls (HC).All these changes could provide these CD4 +CD28 - T-cell characteristics that might be involved in the pathogenesis of MS, turning this T-cell subset into a potential target for future therapeutic strategies. © 2011 Elsevier B.V. Source

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