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Autoantibodies specific to hnRNP K: a new diagnostic marker for immune pathophysiology in aplastic anemia

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Abstract

To identify a new diagnostic marker for the immune pathophysiology of aplastic anemia (AA), we screened sera of immune-mediated AA patients for the presence of antibodies (Abs) specific to proteins derived from a leukemia cell line UT-7 using two-dimensional electrophoresis followed by immunoblotting. The target proteins were identified by peptide mass fingerprinting. Heterogeneous nuclear ribonucleoprotein (hnRNP) K was identified as a novel autoantigen. An enzyme-linked immunosorbent assay revealed high titers of anti-hnRNP K Abs in 85 (31%) of 273 patients with AA. Sixty-four patients received antithymocyte globulin and cyclosporine after undergoing screening for anti-hnRNP K Ab, anti-DRS-1 Ab, anti-moesin Ab, and paroxysmal nocturnal hemoglobinuria (PNH)-type cells. Twenty (87%) of 23 patients with the presence of anti-hnRNP K Abs responded to the immunosuppressive therapy (IST), while 19 (46%) of 41 patients without the presence of anti-hnRNP K Abs responded. A multivariate analysis showed only PNH-type cells and anti-hnRNP K Abs to be significant factors for the prediction of a good response to IST. The detection of anti-hnRNP K Abs as well as PNH-type cells may therefore be useful for diagnosing the immune pathophysiology of AA.

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Acknowledgments

The authors would like to thank R. Oumi and T. Tanaka of Cellular Transplantation Biology of Kanazawa University who provided some technical assistance and all of the BMF study groups who provided sera of patients to this study. This work was supported by a grant from Grant-in-Aid for Scientific Research from the Ministry of Education, Science, Technology, Sports and Culture of Japan (KAKENHI No. 21390291) and grants from the Research Committee for Idiopathic Hematopoietic Disorders, the Ministry of Health, Labor, and Welfare, Japan.

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Authors and Affiliations

  1. Cellular Transplantation Biology, Kanazawa University Graduate School of Medical Science, 13-1 Takaramachi, Kanazawa, 920-8641, Japan

    Zhirong Qi, Hiroyuki Takamatsu, J. Luis Espinoza, Xuzhang Lu, Naomi Sugimori, Hirohito Yamazaki & Shinji Nakao

  2. West China Medical Center, Sichuan University, Chengdu, China

    Zhirong Qi

  3. Biomolecular Characterization Unit, Frontier Technology Center, Kyoto University Graduate School of Medicine, Kyoto, Japan

    Katsuya Okawa

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  1. Zhirong Qi
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Correspondence to Shinji Nakao.

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Qi, Z., Takamatsu, H., Espinoza, J.L. et al. Autoantibodies specific to hnRNP K: a new diagnostic marker for immune pathophysiology in aplastic anemia. Ann Hematol 89, 1255–1263 (2010). https://doi.org/10.1007/s00277-010-1020-3

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  • DOI: https://doi.org/10.1007/s00277-010-1020-3

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