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

• Published in: Frontiers in immunology 2019-11, Vol.10, p.2755-2755
• Main Authors: Castaño-Núñez, Ángel, Montes-Cano, Marco-Antonio, García-Lozano, José-Raúl, Ortego-Centeno, Norberto, García-Hernández, Francisco-José, Espinosa, Gerard, Graña-Gil, Genaro, Sánchez-Bursón, Juan, Juliá, María-Rosa, Solans, Roser, Blanco, Ricardo, Barnosi-Marín, Ana-Celia, Gómez de la Torre, Ricardo, Fanlo, Patricia, Rodríguez-Carballeira, Mónica, Rodríguez-Rodríguez, Luis, Camps, Teresa, Castañeda, Santos, Alegre-Sancho, Juan-Jose, Martín, Javier, González-Escribano, María-Francisca
• Format: Article
• Language: English
• Subjects: Behçet's disease; functional polymorphisms; HLA; Immunology; KIR; NK cells
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2019.02755

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 KIR3DL1 004 was lower in patients than in controls (0.15 vs. 0.20, = 0.005, Pc = 0.015; OR = 0.70; 95% CI 0.54-0.90) in both B51 positive and negative individuals. KIR3DL1 004, 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.