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Blood, 15 October 2004, Vol. 104, No. 8, pp. 2425-2431. Prepublished online as a Blood First Edition Paper on June 24, 2004; DOI 10.1182/blood-2004-05-1839. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-05-1839v1 104/8/2425    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 Feng, X. Articles by Nakao, S. Search for Related Content PubMed PubMed Citation Articles by Feng, X. Articles by Nakao, S. Related Collections Hematopoiesis and Stem Cells Immunobiology Red Cells Free Research Articles Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Diazepam-binding inhibitor-related protein 1: a candidate autoantigen in acquired aplastic anemia patients harboring a minor population of paroxysmal nocturnal hemoglobinuria–type cells Xingmin Feng, Tatsuya Chuhjo, Chiharu Sugimori, Takeharu Kotani, Xuzhang Lu, Akiyoshi Takami, Hiroyuki Takamatsu, Hirohito Yamazaki, and Shinji Nakao From the Cellular Transplantation Biology, Kanazawa University Graduate School of Medical Science, Ishikawa, Japan; and the Protected Environmental Unit, Kanazawa University Hospital, Kanazawa, Ishikawa, Japan. To identify candidate antigens in aplastic anemia (AA), we screened proteins derived from a leukemia cell line with serum of an AA patient and identified diazepam-binding inhibitor-related protein 1 (DRS-1). Enzyme-linked immunosorbent assay (ELISA) revealed high titers of anti–DRS-1 antibodies (DRS-1 Abs) in 27 (38.0%) of 71 AA patients displaying increased paroxysmal nocturnal hemoglobinuria (PNH)–type cells (PNH+), 2 (6.3%) of 32 PNH– AA patients, 5 (38.5%) of 13 PNH+ myelodysplastic syndrome (MDS) patients, and none of 42 PNH– MDS patients. DRS-1 gene was abundantly expressed in myeloid leukemia cell lines and in CD34+ cells derived from healthy individuals. Stimulation of T cells from an AA patient displaying high DRS-1 Abs with a putative CD4+ T-cell epitope (amino acid residues [aa's] 191-204) presented by HLA-DR15, which overlapped with a hot spot (aa's 173-198) of DRS-1 Ab epitopes, gave rise to T cells cytotoxic for L cells (murine fibroblasts) that were transfected with DRB1*1501 and DRS-1. Enzyme-linked immunospot assay demonstrated increased frequency of T-cell precursors specific to the DRS-1 peptide in other HLA-DR15+ AA patients displaying high DRS-1 Ab titers. These findings indicate that DRS-1 may serve as an autoantigen eliciting immune attack against hematopoietic stem cells in a subset of AA patients characterized by increased PNH-type cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. L. Espinoza, H. Takamatsu, X. Lu, Z. Qi, and S. Nakao Anti-moesin antibodies derived from patients with aplastic anemia stimulate monocytic cells to secrete TNF-{alpha} through an ERK1/2-dependent pathway Int. Immunol., August 1, 2009; 21(8): 913 - 923. [Abstract] [Full Text] [PDF] H. Takamatsu, J. L. Espinoza, X. Lu, Z. Qi, K. Okawa, and S. Nakao Anti-Moesin Antibodies in the Serum of Patients with Aplastic Anemia Stimulate Peripheral Blood Mononuclear Cells to Secrete TNF-{alpha} and IFN-{gamma} J. Immunol., January 1, 2009; 182(1): 703 - 710. [Abstract] [Full Text] [PDF] K. Kurosu, Y. Takiguchi, O. Okada, N. Yumoto, S. Sakao, Y. Tada, Y. Kasahara, N. Tanabe, K. Tatsumi, M. Weiden, et al. Identification of Annexin 1 as a Novel Autoantigen in Acute Exacerbation of Idiopathic Pulmonary Fibrosis J. Immunol., July 1, 2008; 181(1): 756 - 767. [Abstract] [Full Text] [PDF] H. Takamatsu, X. Feng, T. Chuhjo, X. Lu, C. Sugimori, K. Okawa, M. Yamamoto, S. Iseki, and S. Nakao Specific antibodies to moesin, a membrane-cytoskeleton linker protein, are frequently detected in patients with acquired aplastic anemia Blood, March 15, 2007; 109(6): 2514 - 2520. [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] M. Battiwalla, T. Hahn, M. Radovic, H. Roy, A. Wahab, E. Duman, R. Bajwa, S. Padmanabhan, J. Becker, A. J. Barrett, et al. Human leukocyte antigen (HLA) DR15 is associated with reduced incidence of acute GVHD in HLA-matched allogeneic transplantation but does not impact chronic GVHD incidence Blood, March 1, 2006; 107(5): 1970 - 1973. [Abstract] [Full Text] [PDF] C. Sugimori, T. Chuhjo, X. Feng, H. Yamazaki, A. Takami, M. Teramura, H. Mizoguchi, M. Omine, and S. Nakao Minor population of CD55-CD59- blood cells predicts response to immunosuppressive therapy and prognosis in patients with aplastic anemia Blood, February 15, 2006; 107(4): 1308 - 1314. [Abstract] [Full Text] [PDF] N. S. Young Pathophysiologic Mechanisms in Acquired Aplastic Anemia Hematology, January 1, 2006; 2006(1): 72 - 77. [Abstract] [Full Text] [PDF]

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