title: Killer cell immunoglobulin-like receptor genes in Spanish multiple sclerosis patients.
abstract: Killer cell immunoglobulin-like receptors (KIRs) are regulators of cytolytic activity of natural killer and certain T cells through interactions with human leukocyte antigen (HLA) class I ligands. KIRs have been shown to contribute to the pathogenesis of several autoimmune diseases, but their role in multiple sclerosis (MS) is still unclear. Here we determined the influence of KIR genes and their HLA class I ligands on susceptibility to MS and on the response to interferon-beta treatment in a Spanish population. KIR and HLA genotyping were performed in 200 MS patients and 200 controls. Significantly higher frequencies were found for KIR2DL5 and KIR3DS1 genes in MS patients and the carriage of the KIR2DL1 gene was associated with a higher progression index. Moreover, the frequency of the HLA-Bw4 motif was significantly reduced in MS patients. The KIR2DL1 and HLA-C2 matches were more frequent in MS patients, whereas the KIR3DL1 and HLA-Bw4 matches were more frequent in healthy controls. Nevertheless, non significant associations were found between all the KIR genes and therapeutic response to interferon-beta. Our results confirm that the carriage of HLA-Bw4 is a protective factor in MS and suggest that KIR2DL5 and KIR3DS1 may have a predisposing role in the disease.
authors.affiliation: Research Laboratory, Clinical Neurosciences Institute, Carlos Haya Regional University Hospital and Fundación IMABIS, Hospital Civil, Pab. 5, Sótano, 29009 Málaga, Spain.
authors.forename: Juan A
authors.initials: JA
authors.lastname: García-León
authors.forename: María J
authors.initials: MJ
authors.lastname: Pinto-Medel
authors.forename: Lucía
authors.initials: L
authors.lastname: García-Trujillo
authors.forename: Carlos
authors.initials: C
authors.lastname: López-Gómez
authors.forename: Begoña
authors.initials: B
authors.lastname: Oliver-Martos
authors.forename: Isidro
authors.initials: I
authors.lastname: Prat-Arrojo
authors.forename: Carmen
authors.initials: C
authors.lastname: Marín-Bañasco
authors.forename: Margarita
authors.initials: M
authors.lastname: Suardíaz-García
authors.forename: Rafael
authors.initials: R
authors.lastname: Maldonado-Sanchez
authors.forename: Oscar
authors.initials: O
authors.lastname: Fernández-Fernández
authors.forename: Laura
authors.initials: L
authors.lastname: Leyva-Fernández
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D015235:HLA-B Antigens / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use; D016899:Interferon-beta / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology; D016133:Polymerase Chain Reaction; D054340:Receptors, KIR / Q000235:genetics* / Q000276:immunology; D013030:Spain; D055815:Young Adult
chemical_list: D015235:HLA-B Antigens; C042388:HLA-Bw4 antigen; D007155:Immunologic Factors; D054340:Receptors, KIR; D016899:Interferon-beta