title: Possible pathogenic role of the transmembrane isoform of CD160 NK lymphocyte receptor in paroxysmal nocturnal hemoglobinuria.
abstract: PIGA mutations in paroxysmal nocturnal hemoglobinuria (PNH) patients lead to a glycosylphosphatidylinositol (GPI)-linked membrane proteins expression deficiency. Herein, we report the constitutive expression of the transmembrane CD160 (CD160-TM) activating receptor on non PIGA-mutated PNH patients circulating NK cells. In healthy individuals, only the GPI-anchored isoform of CD160 receptors is expressed on the circulating NK lymphocytes, while the transmembrane isoform appears after ex vivo activation. Similarly to CD160-GPI, we identified CD160-TM as a receptor for the MHC class I molecules. We demonstrate that PNH patients NK lymphocytes spontaneously produce significant amounts of IFN-γ that is inhibited by anti-CD160-TM or anti-MHC class I mAbs. These results indicate that circulating NK cells from PNH patients exhibit a self-MHC class I molecule reactive effector function, which could be mediated through the recruitment of CD160-TM receptor. Our data provide new insights regarding the possible role of CD160-TM on PNH patients NK lymphocytes and in the pathogenesis of the disease.
authors.affiliation: INSERM U976, F-75475 Paris, France.
authors.forename: J
authors.initials: J
authors.lastname: Giustiniani
authors.forename: S S
authors.initials: SS
authors.lastname: Alaoui
authors.forename: A
authors.initials: A
authors.lastname: Marie-Cardine
authors.forename: J
authors.initials: J
authors.lastname: Bernard
authors.forename: D
authors.initials: D
authors.lastname: Olive
authors.forename: C
authors.initials: C
authors.lastname: Bos
authors.forename: A
authors.initials: A
authors.lastname: Razafindratsita
authors.forename: A
authors.initials: A
authors.lastname: Petropoulou
authors.forename: R P
authors.initials: RP
authors.lastname: de Latour
authors.forename: P
authors.initials: P
authors.lastname: Le Bouteiller
authors.forename: M
authors.initials: M
authors.lastname: Bagot
authors.forename: G
authors.initials: G
authors.lastname: Socié
authors.forename: A
authors.initials: A
authors.lastname: Bensussan
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D002460:Cell Line; D002675:Child, Preschool; D005260:Female; D058851:GPI-Linked Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015870:Gene Expression; D015789:HLA-A2 Antigen / Q000276:immunology / Q000378:metabolism; D006457:Hemoglobinuria, Paroxysmal / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011485:Protein Binding / Q000276:immunology; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011971:Receptors, Immunologic / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; C114505:CD160 protein, human; D058851:GPI-Linked Proteins; D015789:HLA-A2 Antigen; D020033:Protein Isoforms; D011971:Receptors, Immunologic; D007371:Interferon-gamma