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This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Schubert, J. Articles by Schmidt, R. E. Search for Related Content PubMed PubMed Citation Articles by Schubert, J. Articles by Schmidt, R. E. Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  The PIG-anchoring defect in NK lymphocytes of PNH patients J Schubert, P Uciechowski, P Delany, HJ Tischler, W Kolanus and RE Schmidt Abt. Immunologie und Transfusionsmedizin, Medizinische Hochschule Hannover, Federal Republic of Germany. Paroxysmal nocturnal hemoglobinuria (PNH) is clinically characterized by intravascular hemolysis, hemoglobinuria, iron deficiency anemia, and venous thrombosis. Pathophysiologically the disease has now been generally accepted as an acquired defect of phosphatidylinositol glycan (PIG)-anchored molecules on the cell surface of bone marrow-derived cells. This defect is functionally characterized by an abnormal susceptibility to complement-mediated lysis and has been described on erythrocytes, granulocytes, monocytes, and platelets. In contrast, contradictory data exist so far on the involvement of lymphocytes and natural killer (NK) cells. Using monoclonal antibodies (MoAbs) against newly defined PIG-linked surface structures such as CD48, CD55, and CD59, which are homogeneously expressed on lymphocytes of normal donors, we analyzed lymphocytes and their subpopulations in nine PNH patients by two color immunofluorescence. Our results showed that CD3+ T cells as well as CD16+ NK cells are at least partially involved in the deficient PIG-molecule surface expression. To more clearly define the defect in PNH, we generated NK clones from a PNH patient. Phenotypic analysis of these NK clones showed that they either were positive (n = 3) for PIG-linked surface structures such as CD48, CD55, and CD59 (eg, NKP1) or were completely negative (n = 7) for all of them (eg, NKP1). In functional tests the PIG-molecule negative clone NKP2 showed increased susceptibility to human complement compared with the PIG molecule positive clone NKP1. When analyzing the mRNA levels of the PIG-linked molecules CD55 and CD59 there was no difference at all between the two clones. We conclude from our data that NK cells as well as other lymphocyte subpopulations are involved in the PIG-linkage defect of PNH. These NK clones with differential expression of PIG- linked surface structures present for the first time ex vivo mutant cell lymphocyte lines that carry the defect leading to PIG deficiency in PNH. Volume 76, Issue 6, pp. 1181-1187, 09/15/1990 Copyright © 1990 by The American Society of Hematology CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. Poggi, S. Negrini, M. R. Zocchi, A.-M. Massaro, L. Garbarino, S. Lastraioli, L. Gargiulo, L. Luzzatto, and R. Notaro Patients with paroxysmal nocturnal hemoglobinuria have a high frequency of peripheral-blood T cells expressing activating isoforms of inhibiting superfamily receptors Blood, October 1, 2005; 106(7): 2399 - 2408. [Abstract] [Full Text] [PDF] Stephen. J. Richards, Derek. R. Norfolk, D. M. Swirsky, and P. Hillmen Lymphocyte Subset Analysis and Glycosylphosphatidylinositol Phenotype in Patients With Paroxysmal Nocturnal Hemoglobinuria Blood, September 1, 1998; 92(5): 1799 - 1806. [Abstract] [Full Text] [PDF]

	Copyright © 1990 by American Society of Hematology         Online ISSN: 1528-0020