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
Current Molecular Medicine
Title: Possible Pathogenic Role of the Transmembrane Isoform of CD160 NK Lymphocyte Receptor in Paroxysmal Nocturnal Hemoglobinuria
Volume: 12 Issue: 2
Author(s): 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 and A. Marie-Cardine
Affiliation:
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
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
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Giustiniani J., Sabour-Alaoui S., Bernard J., Olive D., Bos C., Razafindratsita A., Petropoulou A., de Latour R.P., Le Bouteiller P., Bagot M., Socie G., Bensussan A. and Marie-Cardine A., Possible Pathogenic Role of the Transmembrane Isoform of CD160 NK Lymphocyte Receptor in Paroxysmal Nocturnal Hemoglobinuria, Current Molecular Medicine 2012; 12 (2) . https://dx.doi.org/10.2174/156652412798889081
DOI https://dx.doi.org/10.2174/156652412798889081 |
Print ISSN 1566-5240 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5666 |
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