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Blood, 15 December 2003, Vol. 102, No. 13, pp. 4567-4575. Prepublished online as a Blood First Edition Paper on August 28, 2003; DOI 10.1182/blood-2002-11-3409. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-11-3409v1 102/13/4567    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 Hirano, N. Articles by Nadler, L. M. Search for Related Content PubMed PubMed Citation Articles by Hirano, N. Articles by Nadler, L. M. Related Collections Hematopoiesis and Stem Cells Immunobiology Red Cells Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  RED CELLS Autoantibodies frequently detected in patients with aplastic anemia Naoto Hirano, Marcus O. Butler, Michael S. von Bergwelt-Baildon, Britta Maecker, Joachim L. Schultze, Kevin C. O'Connor, Peter H. Schur, Seiji Kojima, Eva C. Guinan, and Lee M. Nadler From the Departments of Medical Oncology and Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA; Department of Medicine, Brigham and Women's Hospital, Boston, MA; Laboratory of Molecular Immunology, Center for Neurologic Disease, Department of Neurology, Brigham and Women's Hospital, Boston, MA; Department of Medicine, Harvard Medical School, Boston, MA; and Department of Pediatrics, Nagoya University, Japan. Although accumulating evidence strongly suggests that aplastic anemia (AA) is a T cell-mediated autoimmune disease, no target antigens have yet been described for AA. In autoimmune diseases, target autoantigens frequently induce not only cellular T-cell responses but also humoral B-cell responses. We hypothesized that the presence of antigen-specific autoantibodies could be used as a "surrogate marker" for the identification of target T-cell autoantigens in AA patients. We screened a human fetal liver library for serologic reactivity against hematopoietic stem/progenitor cell antigens and isolated 32 genes. In 7 of 18 AA patients, an immunoglobulin G (IgG) antibody response was detected to one of the genes, kinectin, which is expressed in all hematopoietic cell lineages tested including CD34+ cells. No response to kinectin was detected in healthy volunteers, multiply transfused non-AA patients, or patients with other autoimmune diseases. Epitope mapping of IgG autoantibodies against kinectin revealed that the responses to several of the epitopes were shared by different AA patients. Moreover, CD8+ cytotoxic T cells raised against kinectin-derived peptides suppressed the colony formation of granulocyte macrophage colony-forming units (CFU-GMs) in an HLA class I-restricted fashion. These results suggest that kinectin may be a candidate autoantigen that is involved in the pathophysiology of AA. (Blood. 2003;102:4567-4575) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: F. S. Hodi, M. Butler, D. A. Oble, M. V. Seiden, F. G. Haluska, A. Kruse, S. MacRae, M. Nelson, C. Canning, I. Lowy, et al. Immunologic and clinical effects of antibody blockade of cytotoxic T lymphocyte-associated antigen 4 in previously vaccinated cancer patients PNAS, February 26, 2008; 105(8): 3005 - 3010. [Abstract] [Full Text] [PDF] N. S. Young, R. T. Calado, and P. Scheinberg Current concepts in the pathophysiology and treatment of aplastic anemia Blood, October 15, 2006; 108(8): 2509 - 2519. [Abstract] [Full Text] [PDF] N. Hirano, M. O. Butler, Z. Xia, A. Berezovskaya, A. P. Murray, S. Ansen, S. Kojima, and L. M. Nadler Identification of an immunogenic CD8+ T-cell epitope derived from {gamma}-globin, a putative tumor-associated antigen for juvenile myelomonocytic leukemia Blood, October 15, 2006; 108(8): 2662 - 2668. [Abstract] [Full Text] [PDF] X. Feng, T. Chuhjo, C. Sugimori, T. Kotani, X. Lu, A. Takami, H. Takamatsu, H. Yamazaki, and S. Nakao Diazepam-binding inhibitor-related protein 1: a candidate autoantigen in acquired aplastic anemia patients harboring a minor population of paroxysmal nocturnal hemoglobinuria-type cells Blood, October 15, 2004; 104(8): 2425 - 2431. [Abstract] [Full Text] [PDF]

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