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Prepublished online as a Blood First Edition Paper on August 28, 2003; DOI 10.1182/blood-2002-11-3409.
Submitted November 8, 2002
Accepted August 5, 2003
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
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Depatment of Medicine, Brigham and Women's Hospital, Boston, MA, USA; Department of Medicine, Harvard Medical School, Boston, MA, USA
Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Laboratory of Molecular Immunology, Center for Neurologic Disease, Department of Neurology, Brigham and Women's Hospital, Boston, MA, USA; Department of Pediatrics, Nagoya University, Nagoya, Aichi, Japan
* Corresponding author; email: Naoto_Hirano{at}dfci.harvard.edu.
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 out of 18 AA patients, an 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 CFU-GM 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.
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