Association of Functional Polymorphisms of KIR3DL1/DS1 With Behçet's Disease

Behçet's disease (BD) is an immune-mediated vasculitis related to imbalances between the innate and adaptive immune response. Infectious agents or environmental factors may trigger the disease in genetically predisposed individuals. HLA-B51 is the genetic factor stronger associated with the dis...

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Autores: Castaño-Núñez, Ángel, Montes-Cano, Marco-Antonio, García-Lozano, José-Raúl, Ortego-Centeno, Norberto|||0000-0003-2325-0937, García-Hernández, Francisco-José, Espinosa, Gerard|||0000-0003-1336-0163, Graña, Jenaro|||0000-0001-9041-8117, Sánchez Bursón, Juan, Juliá, María Rosa, Solans, Roser|||0000-0002-0058-1293, Blanco, Ricardo|||0000-0003-2344-2285, Barnosi-Marín, Ana-Celia, Gómez de la Torre, Ricardo, Fanlo, Patricia, Rodríguez-Carballeira, Mónica|||0000-0002-8802-0238, Rodriguez-Rodriguez, Luis|||0000-0002-2869-7861, Camps i Miró, Teresa, Castañeda, Santos|||0000-0002-7748-853X, Alegre-Sancho, Juan José|||0000-0003-1641-0875, Martín, Javier|||0000-0002-2202-0622, González-Escribano, María Francisca
Tipo de recurso: artículo
Fecha de publicación:2019
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:223419
Acceso en línea:https://ddd.uab.cat/record/223419
https://dx.doi.org/urn:doi:10.3389/fimmu.2019.02755
Access Level:acceso abierto
Palabra clave:Behçet's disease
HLA
KIR
NK cells
Functional polymorphisms
Descripción
Sumario:Behçet's disease (BD) is an immune-mediated vasculitis related to imbalances between the innate and adaptive immune response. Infectious agents or environmental factors may trigger the disease in genetically predisposed individuals. HLA-B51 is the genetic factor stronger associated with the disease, although the bases of this association remain elusive. NK cells have also been implicated in the etiopathogenesis of BD. A family of NK receptors, Killer-cell Immunoglobulin-like Receptor (KIR), with a very complex organization, is very important in the education and control of the NK cells by the union to their ligands, most of them, HLA class I molecules. This study aimed to investigate the contribution of certain KIR functional polymorphisms to the susceptibility to BD. A total of 466 BD patients and 444 healthy individuals were genotyped in HLA class I (A, B, and C). The set of KIR genes and the functional variants of KIR3DL1/DS1 and KIR2DS4 were also determined. Frequency of KIR3DL1004 was lower in patients than in controls (0.15 vs. 0.20, P = 0.005, Pc = 0.015; OR = 0.70; 95% CI 0.54-0.90) in both B51 positive and negative individuals. KIR3DL1004, which encodes a misfolded protein, is included in a common telomeric haplotype with only one functional KIR gene, KIR3DL2. Both, KIR3DL1 and KIR3DL2 sense pathogen-associated molecular patterns but they have different capacities to eliminate them. The education of the NK cells depending on the HLA, the balance of KIR3DL1/KIR3DL2 licensed NK cells and the different capacities of these receptors to eliminate pathogens could be involved in the etiopathogenesis of BD.