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Título : Influence of CTLA-4 gene polymorphism in autoimmune and infectious diseases
Autor : Fernandez-Mestre, Mercedes
Sánchez, Karen
Balbás, Omar
Gendzekhzadze, Ketevan
Ogando, Violeta
Cabrera, Maira
Layrisse, Zulay
Palabras clave : Infectio diseases
Autoimmune disease
gene polimorphims
Fecha de publicación : Apr-2009
Editorial : Elsevier
Citación : Human Immunology 70 (2009) 532–535
Citación : 70;
Resumen : Cell-mediated immunity requires costimulatory activity to initiate or inhibit antigen-specific T-cell responses. CTLA-4 is an inhibitory receptor expressed by activated and regulatory T cells. The single nucleotide polymorphism (SNP) 49 A/G of the CTLA-4 gene alters intracellular distribution of CTLA-4, interleukin-2 production, and, as a consequence, T-cell proliferation. The aim of this study was to analyze the only coding SNP CTLA-4 49 A/G polymorphism in patients with either infectious (Chagas’s, Dengue, and American cutaneous leishmaniasis) or autoimmune diseases (myasthenia gravis, pemphigus, and psoriasis). No statistically significant differences were reported when all patients of each disease group were compared with healthy individuals. However, the 49 G/G genotype was moderately increased in pemphigus and myasthenia gravis. Patients with diffuse cutaneous leishmaniasis (DCL) exhibited an increased frequency of the A/G 49 genotype compared with patients with localized cutaneous leishmaniasis (LCL; p 0.009; odds ratio [OR] 4.25; 95% confidence interval [CI] 1.245–14.501) and intermediate cutaneous leishmaniasis (ICL; p 0.027; OR 4.44; 95% CI 1.273–15.516), indicating that the heterozygous genotype, associated with overactivation of T-cell proliferation, could confer susceptibility to the development of the more severe clinical form of cutaneous leishmaniasis. The A/A 49 genotype was increased in LCL patients compared with DCL patients (p 0.019; OR 0.25; 95% CI 0.067–0.953), indicating that this genotype, which has been associated with normal proliferation of T cells, could confer protection to the development of DCL. The results indicate that the polymorphism of CTLA-4 is an important genetic factor associated with risk or protection for the development of diffuse cutaneous leishmaniasis and has influence in the pathogenesis of autoimmune diseases. However, other closely linked candidate genes in linkage disequilibrium with CTLA4, such as CD28 and ICOS, could be associated with the development of autoimmune and infectious disease.
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