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Blood, 15 March 2007, Vol. 109, No. 6, pp. 2514-2520.
Prepublished online as a Blood First Edition Paper on November 16, 2006; DOI 10.1182/blood-2006-07-036715.
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Submitted July 25, 2006
Accepted October 24, 2006
Specific antibodies to moesin, a membrane-cytoskeleton linker protein, are frequently detected in patients with acquired aplastic anemia
Hiroyuki Takamatsu, Xingmin Feng, Tatsuya Chuhjo, Xuzhang Lu, Chiharu Sugimori, Katsuya Okawa, Miyuki Yamamoto, Shoichi Iseki, and Shinji Nakao*
Cellular Transplantation Biology, Div. of Cancer Medicine, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan
Internal Medicine, NTT WEST Kanazawa Hospital, Kanazawa, Japan
Biomolecular Characterization Unit, Kyoto University Graduate School of Medicine, Kyoto, Japan
Department of Histology and Embryology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan
* Corresponding author; email: snakao{at}med3.m.kanazawa-u.ac.jp.
To identify novel autoantibodies in acquired aplastic anemia (AA), we screened the sera of AA patients possessing small populations of paroxysmal nocturnal hemoglobinuria (PNH)-type cells for the presence of antibodies (Abs) which recognize proteins derived from a leukemia cell line, UT-7. Immunoblotting using proteins derived from lysates or culture supernatants of UT-7 cells revealed the presence of IgG Abs specific to an 80 kD protein. Peptide mass fingerprinting identified this 80 kD protein as moesin. Enzyme-linked immunosorbent assay (ELISA) using recombinant moesin showed high titers of anti-moesin Abs in 25 (37%) of 67 AA patients. Moesin was secreted from several myeloid leukemia cell lines other than UT-7, such as OUN-1 and K562, as an exosomal protein. The presence of anti-moesin Abs was significantly correlated with the presence of PNH-type cells and anti-diazepam-binding inhibitor-related protein-1 (DRS-1) Abs. AA patients that did not show any of these three markers tended to respond poorly to immunosuppressive therapy. These findings suggest that a B-cell response to moesin, possibly derived from hematopoietic cells, frequently occurs in patients with AA and that detection of anti-moesin Abs in combination with other markers may be useful in diagnosing immune pathophysiology in AA patients.

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