RESUMEN
Multiple sclerosis (MS) patients, with a second autoimmune disease after lymphocyte depletion, had elevated serum IL-21 before and after treatment which correlated to IL21 genotypes. In addition, the IL21 gene has been associated to several other autoimmune diseases. However, in a Spanish population there was no association to MS. Here, in a Swedish cohort (2090 MS cases and 1732 controls) 12 single nucleotide polymorphisms (SNPs) tagging IL21 were not associated to disease. There was no interaction with risk alleles of IL21R and HLA-DRB1*15. Lack of genetic association was confirmed in a meta-analysis with pooled data from the present study and the Spanish study. In conclusion, IL21 has not been shown to be a major risk gene for MS.
Asunto(s)
Cadenas HLA-DRB1/genética , Subunidad alfa del Receptor de Interleucina-21/genética , Interleucinas/genética , Esclerosis Múltiple/genética , Polimorfismo de Nucleótido Simple , Alelos , Estudios de Cohortes , Epistasis Genética , Femenino , Predisposición Genética a la Enfermedad , Humanos , Masculino , Factores de Riesgo , SueciaRESUMEN
Rat chromosome 1 harbors overlapping quantitative trait loci (QTL) for cytokine production and experimental models of inflammatory diseases. We fine-dissected this region that regulated cytokine production, myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE), anti-MOG antibodies and pristane-induced arthritis (PIA) in advanced intercross lines (AILs). Analysis in the tenth and twelfth generation of AILs resolved the region in two narrow QTL, Eae30 and Eae31. Eae30 showed linkage to MOG-EAE, anti-MOG antibodies and levels of interleukin-6 (IL-6). Eae31 showed linkage to EAE, PIA, anti-MOG antibodies and levels of tumor necrosis factor (TNF) and IL-6. Confidence intervals defined a limited set of potential candidate genes, with the most interesting being RGMA, IL21R and IL4R. We tested the association with multiple sclerosis (MS) in a Nordic case-control material. A single nucleotide polymorphism in RGMA associated with MS in males (odds ratio (OR)=1.33). Polymorphisms of RGMA also correlated with changes in the expression of interferon-gamma (IFN-gamma) and TNF in cerebrospinal fluid of MS patients. In IL21R, there was one positively associated (OR=1.14) and two protective (OR=0.87 and 0.68) haplotypes. One of the protective haplotypes correlated to lower IFN-gamma expression in peripheral blood mononuclear cells of MS patients. We conclude that RGMA and IL21R and their pathways are crucial in MS pathogenesis and warrant further studies as potential biomarkers and therapeutic targets.
Asunto(s)
Encefalomielitis Autoinmune Experimental/genética , Proteínas de la Membrana/genética , Esclerosis Múltiple/genética , Proteínas del Tejido Nervioso/genética , Receptores de Interleucina-21/genética , Animales , Femenino , Proteínas Ligadas a GPI , Ligamiento Genético , Haplotipos , Masculino , Polimorfismo de Nucleótido Simple , Sitios de Carácter Cuantitativo , RatasRESUMEN
The authors report the case of a 19-year-old patient with an infectious mononucleosis, causing, 2 days after the onset of symptoms, a spontaneous splenic rupture. Acetyl salicylic acid had been given at the beginning of symptoms including fever and a pharyngitis. The diagnosis was obtained by laparoscopy after failure of sonographic. The patient was discharged 10 days after splenectomy.