22
views
0
recommends
+1 Recommend
1 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Inmunopatogenia de la psoriasis. Impacto en las manifestaciones clínicas y el tratamiento de la enfermedad Translated title: Immunopathogenesis of psoriasis. Impact on clinical manifestations and its treatment

      review-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          La psoriasis es una enfermedad inflamatoria crónica de la piel mediada por células T que afecta a individuos con predisposición genética y presenta varios subtipos clínicos. Se caracteriza por la presencia de placas eritematosas bien definidas, escamosas y de bordes irregulares, que afectan fundamentalmente las regiones de los codos, las rodillas, el cuero cabelludo y el tronco. El alelo HLA-Cw6 del sistema principal de histocompatibilidad está relacionado con la presencia y severidad de la enfermedad. Desde el punto de vista fisiopatogénico, la psoriasis es una enfermedad inmune de tipo Th1, en la que es fundamental el eje IL-23/Th17. Las células Th17 producen las citocinas proinflamatorias (IL-17A, IL-17F, IL-22 e IL-26) que activan los queratinocitos y causan hiperproliferación y mayor producción de citocinas proinflamatorias y péptidos antimicrobianos, los que a su vez reclutan y activan otras células inmunes de la piel inflamada. Se produce así una amplificación de la respuesta inflamatoria que conduce a las manifestaciones clínicas de la enfermedad. El tratamiento de la psoriasis incluye agentes antiinflamatorios tópicos, fototerapia, inmunosupresores sistémicos y agentes biológicos, entre los que se encuentran las proteínas de fusión, los inhibidores del factor de necrosis tumoral alfa y los inhibidores de las interleucinas 12 y 23.

          Translated abstract

          Psoriasis is a T cell-mediated chronic inflammatory disease of the skin. It affects genetically predisposed individuals and presents several subtypes. It is characterized by the presence of well-defined erythematous, scaly, irregular border plaque or lesions, affecting mainly the elbows, knees, scalp, and trunk. The HLA-Cw6 allele of major histocompatibility system is related to the presence and severity of this disease. From the physiopathogenic viewpoint, psoriasis is a Th1-type immune disease in which the axle IL-23/Th17 is fundamental. Th17 cells produce proinflammatory cytokines (IL-17A, IL-17F, IL-22 and IL-26) which activate keratinocytes and cause hyperproliferation and increased production of proinflammatory cytokines and antimicrobial peptides. The latter, in turn, recruit and activate other immune cells of swollen skin. There is thus an amplification of the inflammatory response that leads to clinical manifestations of this disease. The treatment of psoriasis includes topical antiinflammatory agents, phototherapy and systemic immunosuppressive biological agents, including those which are fusion proteins, inhibitors of alpha tumor factor necrosis, and interleukin inhibitors 12 and 23.

          Related collections

          Most cited references107

          • Record: found
          • Abstract: found
          • Article: not found

          Pathogenesis and therapy of psoriasis.

          Psoriasis is one of the most common human skin diseases and is considered to have key genetic underpinnings. It is characterized by excessive growth and aberrant differentiation of keratinocytes, but is fully reversible with appropriate therapy. The trigger of the keratinocyte response is thought to be activation of the cellular immune system, with T cells, dendritic cells and various immune-related cytokines and chemokines implicated in pathogenesis. The newest therapies for psoriasis target its immune components and may predict potential treatments for other inflammatory human diseases.
            Bookmark
            • Record: found
            • Abstract: not found
            • Article: not found

            Novel p19 Protein Engages IL-12p40 to Form a Cytokine, IL-23, with Biological Activities Similar as Well as Distinct from IL-12

              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              A large-scale genetic association study confirms IL12B and leads to the identification of IL23R as psoriasis-risk genes.

              We performed a multitiered, case-control association study of psoriasis in three independent sample sets of white North American individuals (1,446 cases and 1,432 controls) with 25,215 genecentric single-nucleotide polymorphisms (SNPs) and found a highly significant association with an IL12B 3'-untranslated-region SNP (rs3212227), confirming the results of a small Japanese study. This SNP was significant in all three sample sets (odds ratio [OR](common) 0.64, combined P [Pcomb]=7.85x10(-10)). A Monte Carlo simulation to address multiple testing suggests that this association is not a type I error. The coding regions of IL12B were resequenced in 96 individuals with psoriasis, and 30 additional IL12B-region SNPs were genotyped. Haplotypes were estimated, and genotype-conditioned analyses identified a second risk allele (rs6887695) located approximately 60 kb upstream of the IL12B coding region that exhibited association with psoriasis after adjustment for rs3212227. Together, these two SNPs mark a common IL12B risk haplotype (OR(common) 1.40, Pcomb=8.11x10(-9)) and a less frequent protective haplotype (OR(common) 0.58, Pcomb=5.65x10(-12)), which were statistically significant in all three studies. Since IL12B encodes the common IL-12p40 subunit of IL-12 and IL-23, we individually genotyped 17 SNPs in the genes encoding the other chains of these cytokines (IL12A and IL23A) and their receptors (IL12RB1, IL12RB2, and IL23R). Haplotype analyses identified two IL23R missense SNPs that together mark a common psoriasis-associated haplotype in all three studies (OR(common) 1.44, Pcomb=3.13x10(-6)). Individuals homozygous for both the IL12B and the IL23R predisposing haplotypes have an increased risk of disease (OR(common) 1.66, Pcomb=1.33x10(-8)). These data, and the previous observation that administration of an antibody specific for the IL-12p40 subunit to patients with psoriasis is highly efficacious, suggest that these genes play a fundamental role in psoriasis pathogenesis.
                Bookmark

                Author and article information

                Contributors
                Role: ND
                Journal
                hih
                Revista Cubana de Hematología, Inmunología y Hemoterapia
                Rev Cubana Hematol Inmunol Hemoter
                Editorial Ciencias Médicas (Ciudad de la Habana )
                1561-2996
                December 2012
                : 28
                : 4
                : 357-373
                Affiliations
                [1 ] Instituto de Hematología e Inmunología Cuba
                Article
                S0864-02892012000400005
                f0c9c41d-2c88-4e80-ae6a-059fec78fb34

                http://creativecommons.org/licenses/by/4.0/

                History
                Product

                SciELO Cuba

                Self URI (journal page): http://scielo.sld.cu/scielo.php?script=sci_serial&pid=0864-0289&lng=en
                Categories
                HEMATOLOGY

                Hematology
                psoriasis,immunopathogenesis,T cells,IFNa,plasmacytoid dendritic cells,Th17 cells,IL-23/Th17 axis,inmunopatogenia,células T,células dendríticas plasmacitoides,células Th17,eje IL-23/Th17

                Comments

                Comment on this article