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

[ Vol. 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   Pages 188 - 198 ( 11 )

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

Affiliation:

Hopital Saint Louis, INSERM U976, Equerre Bazin, 1 Avenue Claude Vellefaux, 75010 Paris, France., Hopital Saint Louis, INSERM U976, Equerre Bazin, 1 Avenue Claude Vellefaux, 75010 Paris, France.



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