{"id":117690,"date":"2018-03-11T10:47:18","date_gmt":"2018-03-11T10:47:18","guid":{"rendered":"https:\/\/www.deberes.net\/tesis\/sin-categoria\/estudio-de-genes-kir-y-hla-c-y-de-polimorfismos-de-citoquinas-en-pacientes-con-psoriasis\/"},"modified":"2018-03-11T10:47:18","modified_gmt":"2018-03-11T10:47:18","slug":"estudio-de-genes-kir-y-hla-c-y-de-polimorfismos-de-citoquinas-en-pacientes-con-psoriasis","status":"publish","type":"post","link":"https:\/\/www.deberes.net\/tesis\/epidemiologia\/estudio-de-genes-kir-y-hla-c-y-de-polimorfismos-de-citoquinas-en-pacientes-con-psoriasis\/","title":{"rendered":"Estudio de genes kir y hla-c y de polimorfismos de citoquinas en pacientes con psoriasis"},"content":{"rendered":"<h2>Tesis doctoral de <strong> Jose Pardo Sanchez <\/strong><\/h2>\n<p>Resumen  la psoriasis es una enfermedad de curso cr\u00f3nico caracterizada por la presencia de lesiones cut\u00e1neas eritemato-escamosas, y constituye uno de los procesos dermatol\u00f3gicos m\u00e1s frecuentes. Su curso cl\u00ednico es din\u00e1mico e impredecible, y en algunos casos el impacto emocional y f\u00edsico en el paciente que la sufre puede ser muy importante. Su inmunopatolog\u00eda se basa en mecanismos complejos, donde intervienen tanto una respuesta inmunitaria adaptativa, mediada fundamentalmente por c\u00e9lulas th17, como innata, con la participaci\u00f3n de elementos como el tnf-? O los receptores kir (del ingl\u00e9s, killer immunoglobulin-like receptors). Estos receptores son expresados fundamentalmente por las c\u00e9lulas nk, y su funci\u00f3n principal es la de inhibir la actividad citot\u00f3xica de estas c\u00e9lulas tras su uni\u00f3n con ligandos como hla-c. Igualmente, se sabe que el alelo hla-c*06 es el principal determinante gen\u00e9tico en la psoriasis, aunque los estudios en relaci\u00f3n con el mismo realizados en nuestro pa\u00eds son escasos. existe un n\u00famero creciente de observaciones que demuestran que determinados genotipos receptor-ligando kir\/hla-c modulan la acci\u00f3n de las c\u00e9lulas del sistema inmunitario innato a favor de interacciones activadoras que predispondr\u00edan a enfermedades autoinmunitarias como la psoriasis. As\u00ed, con el fin de realizar una descripci\u00f3n inmunol\u00f3gica de nuestros pacientes y de valorar la participaci\u00f3n del sistema inmunitario innato en la enfermedad, en este trabajo se realiz\u00f3 el tipaje de los alelos hla-c y de los genes kir mediante t\u00e9cnicas de reacci\u00f3n en cadena de la polimerasa (pcr), tanto en pacientes con psoriasis como en controles sanos. Adem\u00e1s, mediante tipajes de alta resoluci\u00f3n se determinaron los polimorfismos tipo snp de genes que codifican citoquinas proinflamatorias involucradas en la formaci\u00f3n de la placa psori\u00e1sica (tnf- , il-6, inf-  e il-23).  los resultados obtenidos en este trabajo confirmaron que el alelo hla-c*06 constitu\u00eda un factor de riesgo, especialmente para la psoriasis de debut precoz o tipo i, mientras que el alelo hla-c*07 era sugestivo de protecci\u00f3n. Con respecto a los genes kir, los individuos que carec\u00edan de kir2dl1, los kir2dl2\/l2 homocigotos y los portadores de kir2dl5 mostraban una mayor predisposici\u00f3n a padecer psoriasis. El gen kir2dl5 parec\u00eda actuar de manera sin\u00e9rgica con hla-c*06 sobre la susceptibilidad a padecer la enfermedad. Adem\u00e1s, la presencia de kir2ds2 y kir2ds3 en el genoma del paciente constitu\u00eda un factor de riesgo m\u00e1s espec\u00edfico para la artropat\u00eda psori\u00e1sica. el estudio de la combinaci\u00f3n de los pares receptor-ligando kir\/hla-c revel\u00f3 que la presencia simult\u00e1nea del alotipo hla-c1 no modificaba el efecto de susceptibilidad a la psoriasis observado en los individuos kir2dl2\/l2 homocigotos. Sin embargo, en los pacientes kir2dl2\/l3 heterocigotos la presencia del ligando c1 ejerc\u00eda un efecto protector frente a esta enfermedad, que era adem\u00e1s dependiente de la dosis de este ligando e independiente de la presencia del alelo hla-c*06. Adem\u00e1s, la combinaci\u00f3n de kir2ds1\/ligando c2 se asociaba espec\u00edficamente a la psoriasis tipo i. el estudio de los polimorfismos de citoquinas mostr\u00f3 que los snps tnf -238g&gt;a, il6 -174g&gt;c e infg +874t&gt;a determinaban una mayor susceptibilidad a la psoriasis, especialmente la tipo i. Sin embargo, en el caso del gen tnf el efecto del alelo a pod\u00eda ser subsidiario de un desequilibrio de uni\u00f3n con hla-c*06. Llamaba la atenci\u00f3n que la asociaci\u00f3n de este alelo con la psoriasis se observaba en varones pero no en mujeres. Adem\u00e1s, el polimorfismo il12b -1188a&gt;c se asociaba con un efecto protector modesto. en definitiva, los hallazgos encontrados contribuyen a confirmar el papel del par kir\/hla-c y de algunas citoquinas como el tnf-? En la patogenia de la psoriasis, y hablan a favor de la importancia de la inmunidad innata en esta enfermedad.    abstract  psoriasis is a chronic disease characterized by the presence of erythematous and scaling skin lesions, and it is one of the most frequent dermatologic process. Its clinical course is dynamic and unpredictable, and in some cases the emotional and physical impact in patients can be very important. Its immunopathology is based on complex mechanisms, where either an adaptive immune response, mediated fundamentally by th17 cells, and an innate immune response, with the participation of elements such tnf-? Or killer immunoglobulin-like receptors (kir), are involved. These receptors are mainly expressed by nk cells, and their principal task is to inhibit these cells cytotoxic activity after their binding to ligands such as hla-c molecules. Equally, it is known that hla-c*06 allele is the main genetic factor in psoriasis, however studies related to this allele are hardly to be found in our country.  there is a growing number of studies which demonstrate that certain kir\/hla-c receptor-ligand genotypes modulate the action of cells from the innate immune system supporting activating interactions which would predispose to autoimmune diseases such as psoriasis. Thus, with the aim of performing an immunologic description of our patients and evaluating the participation of the innate immune system in the disease, in this study was carried out the genotyping of hla-c alleles and kir genes by means of polymerase chain reaction techniques, both in patients with psoriasis and in healthy controls. Besides, genotype of snp polymorphisms of genes which codify pro-inflammatory cytokines involved in the formation of psoriatic plaques (tnf-?, Il-6, inf-? And il-23) were identified by high resolution techniques. the results of this study confirmed that hla-c*06 allele is a risk factor, specially for patients with early onset psoriasis, type i, while hla-c*07 allele suggested protection against the disease. Regarding kir genes, individuals who lacked kir2dl1, kir2dl2 homozygotes and kir2dl5 carriers, showed a higher predisposition to suffer from psoriasis. Kir2dl5 gene appeared to act synergistically with hla-c*06 on the susceptibility to suffer from this disease. In addition, presence of kir2ds2 and kir2ds3 in patient&apos;s genome constituted a more specific risk factor for psoriatic arthropathy. the study of the combination of kir\/hla-c receptor-ligand pairs revealed that simultaneous presence of hla-c1 allotype did not modify the susceptibility to suffer from psoriasis observed in kir2dl2\/l2 homozygotes individuals. However, in kir2dl2\/l3 heterozygotes patients, the presence of c1 ligand had a protective effect against the disease, which in addition was dependent on the dose ligand, and independent from the presence of hla-c*06 allele. Moreover, the combination of kir2ds1\/c2-ligand was associated specifically to type i psoriasis. the study of cytokine polymorphisms illustrated that snps tnf -238g&gt;a, il6 -174g&gt;c and infg +874t&gt;a determined a higher susceptibility to psoriasis, specially type i psoriasis. However, in the case of tnf gene, the effect of the a allele could be subsidiary of a linkage disequilibrium with hla-c*06. It was very remarkable that the association of this allele with psoriasis was present in men, but not so in women. Likewise, the il12b -1188a&gt;c polymorphism was associated to a modest protective effect. in conclusion, the findings of this study contribute to confirm the role of kir\/hla-c pair and of certain cytokines such as tnf-? In the pathogenesis of psoriasis, and give us insightful hints of the importance of innate immunity in this disease.<\/p>\n<p>&nbsp;<\/p>\n<h3>Datos acad\u00e9micos de la tesis doctoral \u00ab<strong>Estudio de genes kir y hla-c y de polimorfismos de citoquinas en pacientes con psoriasis<\/strong>\u00ab<\/h3>\n<ul>\n<li><strong>T\u00edtulo de la tesis:<\/strong>\u00a0 Estudio de genes kir y hla-c y de polimorfismos de citoquinas en pacientes con psoriasis <\/li>\n<li><strong>Autor:<\/strong>\u00a0 Jose Pardo Sanchez <\/li>\n<li><strong>Universidad:<\/strong>\u00a0 Murcia<\/li>\n<li><strong>Fecha de lectura de la tesis:<\/strong>\u00a0 23\/06\/2015<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n<h3>Direcci\u00f3n y tribunal<\/h3>\n<ul>\n<li><strong>Director de la tesis<\/strong>\n<ul>\n<li>Ruth Lopez Hernandez<\/li>\n<\/ul>\n<\/li>\n<li><strong>Tribunal<\/strong>\n<ul>\n<li>Presidente del tribunal: Jos\u00e9 Luis Sanchez carazo <\/li>\n<li>Mar\u00eda  rosa Moya quiles (vocal)<\/li>\n<li>alfredo Minguela puras (vocal)<\/li>\n<li>Jorge Mart\u00ednez escribano (vocal)<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Tesis doctoral de Jose Pardo Sanchez Resumen la psoriasis es una enfermedad de curso cr\u00f3nico caracterizada por la presencia de 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