Possible Pathogenic Role of the Transmembrane Isoform of CD160 NK Lymphocyte Receptor in Paroxysmal Nocturnal Hemoglobinuria

J.      Giustiniani; S.      Sabour-Alaoui; J.      Bernard; D.      Olive; C.      Bos; A.      Razafindratsita; A.      Petropoulou; R.P.      de Latour; P.      Le Bouteiller; M.      Bagot; G.      Socie; A.      Bensussan; A.      Marie-Cardine

doi:10.2174/156652412798889081

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

Keywords: Anchored CD160, NK lymphocytes, paroxysmal nocturnal hemoglobinuria, transmembrane, polymorphic genes, haplotypes, apoptosis, signaling pathway, hematopoietic stem cells, mutations, idiopathic aplastic anemia, hypoplastic myelodysplastic syndrome, Eculizumab, thrombocytopenia, immunosuppressive therapy