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
Export Options
About this article
Cite this article as:
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 |
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Concomitant Use of Immunomodulators with Anti-TNF in Crohns Disease: Yes or No?
Current Drug Targets Collateral Damage Control in Cancer Therapy: Defining the Stem Identity in Gliomas
Current Pharmaceutical Design Myeloma Cells and Their Interactions With the Bone Marrow Endothelial Cells
Current Immunology Reviews (Discontinued) Cardiac Toxicity of Antineoplastic Anthracyclines
Current Medicinal Chemistry - Anti-Cancer Agents Phenothiazines and Related Drugs as Multi Drug Resistance Reversal Agents in Cancer Chemotherapy Mediated by p-glycoprotein
Current Cancer Therapy Reviews Genetic Surgery - A Right Strategy to Attack Cancer
Current Gene Therapy Acetylenic Anticancer Agents
Anti-Cancer Agents in Medicinal Chemistry The Role of YY1 in Oncogenesis and Its Potential as a Drug Target in Cancer Therapies
Current Cancer Drug Targets Recent Developments in the Chemical Biology of Epothilones
Current Pharmaceutical Design Tumor Stem Cell Niches: A New Functional Framework for the Action of Anticancer Drugs
Recent Patents on Anti-Cancer Drug Discovery Chlorogenic Acid and Mental Diseases: From Chemistry to Medicine
Current Neuropharmacology Cytotoxic, Apoptotic and DNA Synthesis Inhibitory Effects of Some Thiazole Derivatives
Letters in Drug Design & Discovery Paullones as Inhibitors of Protein Kinases
Current Topics in Medicinal Chemistry Hemangiomas, Angiosarcomas, and Vascular Malformations Represent the Signaling Abnormalities of Pathogenic Angiogenesis
Current Molecular Medicine Archaeosome Immunostimulatory Vaccine Delivery System
Current Drug Delivery Histone Modifications as Molecular Targets in Nasopharyngeal Cancer
Current Medicinal Chemistry Immunotoxins and Neuropeptide-Toxin Conjugates Experimental Applications
Mini-Reviews in Medicinal Chemistry Topical Calcineurin Inhibitors, Pimecrolimus and Tacrolimus
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Microfluidic Methods for Non-Viral Gene Delivery
Current Gene Therapy Non-Celiac Gluten Sensitivity Triggers Gut Dysbiosis, Neuroinflammation, Gut-Brain Axis Dysfunction, and Vulnerability for Dementia
CNS & Neurological Disorders - Drug Targets