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Blood, 15 February 2004, Vol. 103, No. 4, pp. 1383-1390. Prepublished online as a Blood First Edition Paper on October 2, 2003; DOI 10.1182/blood-2003-04-1281. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-04-1281v1 103/4/1383    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Takahashi, Y. Articles by Childs, R. W. Search for Related Content PubMed PubMed Citation Articles by Takahashi, Y. Articles by Childs, R. W. Related Collections Immunobiology Red Cells Transplantation Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY In vitro and in vivo evidence of PNH cell sensitivity to immune attack after nonmyeloablative allogeneic hematopoietic cell transplantation Yoshiyuki Takahashi, J. Philip McCoy, Jr, Cristian Carvallo, Candido Rivera, Takehito Igarashi, Ramaprasad Srinivasan, Neal S. Young, and Richard W. Childs From the Hematology Branch and the Flow Cytometry Core Facility, National Heart, Lung, and Blood Institute, Bethesda, MD; the Urologic Oncology Branch, National Cancer Institute, Bethesda, MD; and the Department of Laboratory Medicine, the Warren Magnusson Clinical Center, National Institutes of Health, Bethesda, MD. It has been proposed that paroxysmal nocturnal hemoglobinuria (PNH) cells may proliferate through their intrinsic resistance to immune attack. To evaluate this hypothesis, we examined the impact of alloimmune pressure on PNH and normal cells in the clinical setting of nonmyeloablative allogeneic hematopoietic cell transplantation (HCT). Five patients with severe PNH underwent HCT from an HLA-matched family donor after conditioning with cyclophosphamide and fludarabine. PNH neutrophils (CD15+/CD66b–/CD16–) were detected in all patients at engraftment, but they subsequently declined to undetectable levels in all cases by 4 months after transplantation. To test for differences in susceptibility to immune pressure, minor histocompatibility antigen (mHa)–specific T-cell lines or clones were targeted against glycosylphosphatidylinositol (GPI)–negative and GPI-positive monocyte and B-cell fractions purified by flow cytometry sorting. Equivalent amounts of interferon- (IFN-) were secreted following coculture with GPI-negative and GPI-positive targets. Furthermore, mHa-specific T-cell lines and CD8+ T-cell clones showed similar cytotoxicity against both GPI-positive and GPI-negative B cells. Presently, all 5 patients survive without evidence of PNH 5 to 39 months after transplantation. These in vitro and in vivo studies show PNH cells can be immunologically eradicated following nonmyeloablative HCT. Relative to normal cells, no evidence for a decreased sensitivity of PNH cells to T-cell–mediated immunity was observed. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: R. A. Brodsky Narrative Review: Paroxysmal Nocturnal Hemoglobinuria: The Physiology of Complement-Related Hemolytic Anemia Ann Intern Med, April 15, 2008; 148(8): 587 - 595. [Full Text] [PDF] C. Parker, M. Omine, S. Richards, J.-i. Nishimura, M. Bessler, R. Ware, P. Hillmen, L. Luzzatto, N. Young, T. Kinoshita, et al. Diagnosis and management of paroxysmal nocturnal hemoglobinuria Blood, December 1, 2005; 106(12): 3699 - 3709. [Full Text] [PDF] J. P. Maciejewski and A. M. Risitano Aplastic Anemia: Management of Adult Patients Hematology, January 1, 2005; 2005(1): 110 - 117. [Abstract] [Full Text] [PDF] T. Igarashi, J. Wynberg, R. Srinivasan, B. Becknell, J. P. McCoy Jr, Y. Takahashi, D. A. Suffredini, W. M. Linehan, M. A. Caligiuri, and R. W. Childs Enhanced cytotoxicity of allogeneic NK cells with killer immunoglobulin-like receptor ligand incompatibility against melanoma and renal cell carcinoma cells Blood, July 1, 2004; 104(1): 170 - 177. [Abstract] [Full Text] [PDF]

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