title: Cutting edge: susceptibility to psoriatic arthritis: influence of activating killer Ig-like receptor genes in the absence of specific HLA-C alleles.
abstract: NK cell activity is partially controlled through interactions between killer Ig-like receptors (KIR) on NK cells and their respective HLA class I ligands. Independent segregation of HLA and KIR genes, along with KIR specificity for particular HLA allotypes, raises the possibility that any given individual may express KIR molecules for which no ligand is present. Inhibitory receptor genes KIR2DL2/3 and KIR2DL1 were present in nearly all subjects sampled in this study, whereas their respective activating homologs, KIR2DS2 and KIR2DS1, are each present in about half of the subjects. In this work we report that subjects with activating KIR2DS1 and/or KIR2DS2 genes are susceptible to developing psoriatic arthritis, but only when HLA ligands for their homologous inhibitory receptors, KIR2DL1 and KIR2DL2/3, are missing. Absence of ligands for inhibitory KIRs could potentially lower the threshold for NK (and/or T) cell activation mediated through activating receptors, thereby contributing to pathogenesis of psoriatic arthritis.
authors.affiliation: Basic Research Program, SAIC-Frederick, MD 21702, USA.
authors.forename: Maureen P
authors.initials: MP
authors.lastname: Martin
authors.forename: George
authors.initials: G
authors.lastname: Nelson
authors.forename: Jeong-Hee
authors.initials: JH
authors.lastname: Lee
authors.forename: Fawnda
authors.initials: F
authors.lastname: Pellett
authors.forename: Xiaojiang
authors.initials: X
authors.lastname: Gao
authors.forename: Judith
authors.initials: J
authors.lastname: Wade
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Wilson
authors.forename: John
authors.initials: J
authors.lastname: Trowsdale
authors.forename: Dafna
authors.initials: D
authors.lastname: Gladman
authors.forename: Mary
authors.initials: M
authors.lastname: Carrington
mesh_terms: D000483:Alleles; D015535:Arthritis, Psoriatic / Q000235:genetics* / Q000276:immunology*; D005786:Gene Expression Regulation / Q000276:immunology*; D005787:Gene Frequency / Q000276:immunology; D020022:Genetic Predisposition to Disease; D015236:HLA-C Antigens / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism*; D008024:Ligands; D011971:Receptors, Immunologic / Q000235:genetics* / Q000378:metabolism; D054340:Receptors, KIR; D054342:Receptors, KIR2DL1; D054343:Receptors, KIR2DL2
chemical_list: D015236:HLA-C Antigens; C515077:KIR2DL2 protein, human; D008024:Ligands; D011971:Receptors, Immunologic; D054340:Receptors, KIR; D054342:Receptors, KIR2DL1; D054343:Receptors, KIR2DL2