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

AuthorsCastaño-Núñez, Á; Montes-Cano, MA; García-Lozano, JR; Ortego-Centeno, N.; García-Hernández, FJ; Espinosa, G; Graña-Gil, Genaro; Sánchez-Bursón, J; Juliá, MR; Solans, R; Blanco, R; Barnosi-Marín, AC; Gómez de la Torre,R; Fanlo, P; Rodríguez-Carballeira, M; Rodríguez-Rodríguez, L; Camps, T; Castañeda, S; Alegre-Sancho, J. J.; Martín, J.; González-Escribano, María Francisca
KeywordsBehçet's disease, HLA, KIR, NK cells, functional polymorphisms
Issue Date2019
PublisherFrontiers Media
CitationFrontiers in Immunology 10: 2755 (2019)
AbstractBehçet'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, P = 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.
Publisher version (URL)http://dx.doi.org/10.3389/fimmu.2019.02755
Identifiersdoi: 10.3389/fimmu.2019.02755
e-issn: 1664-3224
Appears in Collections:(IPBLN) Artículos
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