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Published in: International Journal of Hematology 5/2017

01-11-2017 | Original Article

Screening novel autoantigens targeted by serum IgG autoantibodies in immunorelated pancytopenia by SEREX

Authors: Shanfeng Hao, Rong Fu, Huaquan Wang, Zonghong Shao

Published in: International Journal of Hematology | Issue 5/2017

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Abstract

Immunorelated pancytopenia (IRP) is characterized by pancytopenia caused by autoantibody-mediated destruction or suppression of bone marrow. However, the autoantigens targeted by autoantibodies in IRP remain unclear. In the present study, we screened novel autoantigens in IRP by serological analysis of recombinant cDNA expression libraries and compared anti-UQCR10 antibody levels between IRP and normal controls detected by immunoblotting. Our results indicate that we successfully constructed the K562 cDNA library, which we used to screen seven candidate autoantigens expressed in haematopoietic cells of IRP: ferritin, light polypeptide, ubiquinol-cytochrome c reductase, complex III subunit X (UQCR10), multifunctional methyl-transferase subunit TRM112-like protein isoform 1 (TRMT112), hemoglobin gamma-G, stathmin 1 (STMN1), transcript variant 3, phosphoglycerate kinase 1 (PGK1), and trafficking protein particle complex subunit 4 (TRAPPC4). Six of 17 (35.29%) IRP patients exhibited positive reactivity to UQCR10 antigen, while only one of 10 (10%) of normal controls reacted to UQCR10 antigen. The IRP patients with positive reactivity to UQCR10 antigen exhibited significantly improved total efficiency (6/6) compared with those with negative reactivity (5/11). Thus, UQCR10 may be implicated as one of the autoantigens involved in development of IRP.
Literature
1.
go back to reference He H, Shao Z, Liu H, Song L, Tian P, Cao Z, et al. Immunorelated pancytopenia. Zhonghua Xue Ye Xue Za Zhi. 2001;22:79–82.PubMed He H, Shao Z, Liu H, Song L, Tian P, Cao Z, et al. Immunorelated pancytopenia. Zhonghua Xue Ye Xue Za Zhi. 2001;22:79–82.PubMed
2.
go back to reference Yue LZ, Shao ZH. Research progress on the red cell diseases in China. Chin Med J (Engl). 2012;125:2746–51. Yue LZ, Shao ZH. Research progress on the red cell diseases in China. Chin Med J (Engl). 2012;125:2746–51.
3.
go back to reference He H, Shao Z, Cao Z, Tian P, Cui W, Liu H, et al. Category of bone marrow mononuclear cells Coombs test. Zhonghua Xue Ye Xue Za Zhi. 2000;22:550. He H, Shao Z, Cao Z, Tian P, Cui W, Liu H, et al. Category of bone marrow mononuclear cells Coombs test. Zhonghua Xue Ye Xue Za Zhi. 2000;22:550.
4.
go back to reference Fu R, Shao ZH, Liu H, He H, Jia HR, Sun J, et al. Category, quantity and clinical significance of autoantibodies on bone marrow hematopoietic cells in patients with immunorelated cytopenia. Zhonghua Xue Ye Xue Za Zhi. 2003;24:177–80.PubMed Fu R, Shao ZH, Liu H, He H, Jia HR, Sun J, et al. Category, quantity and clinical significance of autoantibodies on bone marrow hematopoietic cells in patients with immunorelated cytopenia. Zhonghua Xue Ye Xue Za Zhi. 2003;24:177–80.PubMed
5.
go back to reference Wang YH, Fu R, Dong SW, Liu H, Shao ZH. Erythroblastic islands in the bone marrow of patients with immune-related pancytopenia. PLoS One. 2014;9:e95143.CrossRefPubMedPubMedCentral Wang YH, Fu R, Dong SW, Liu H, Shao ZH. Erythroblastic islands in the bone marrow of patients with immune-related pancytopenia. PLoS One. 2014;9:e95143.CrossRefPubMedPubMedCentral
6.
go back to reference Liu H, Fu R, Wang Y, Liu H, Li L, Wang H, et al. Detection and analysis of autoantigens targeted by autoantibodies in immunorelated pancytopenia. Clin Dev Immunol. 2013;2013:297678.PubMedPubMedCentral Liu H, Fu R, Wang Y, Liu H, Li L, Wang H, et al. Detection and analysis of autoantigens targeted by autoantibodies in immunorelated pancytopenia. Clin Dev Immunol. 2013;2013:297678.PubMedPubMedCentral
7.
go back to reference Shao Y, Fu R, Liu H, Wang Y, Ding S, Wang H, et al. IgG autoantibody subclasses altered in immuno-related hemocytopenia. Cell Immunol. 2015;294:13–20.CrossRefPubMed Shao Y, Fu R, Liu H, Wang Y, Ding S, Wang H, et al. IgG autoantibody subclasses altered in immuno-related hemocytopenia. Cell Immunol. 2015;294:13–20.CrossRefPubMed
8.
go back to reference Fu R, Shao ZH, Liu H, Wu YH, Wang HQ, Xing LM. Role of B lymphocyte and its subpopulations in pathogenesis of immunorelated pancytopenia. Chin Med Sci J. 2007;22:199–202.PubMed Fu R, Shao ZH, Liu H, Wu YH, Wang HQ, Xing LM. Role of B lymphocyte and its subpopulations in pathogenesis of immunorelated pancytopenia. Chin Med Sci J. 2007;22:199–202.PubMed
9.
go back to reference Fu R, Shao Z, He H, Liu H, Jia H, Sun J, et al. Quantity and apoptosis-related protein level of B lymphocyte in patients with immunorelated pancytopenia. Zhonghua Xue Ye Xue Za Zhi. 2002;23:236–8.PubMed Fu R, Shao Z, He H, Liu H, Jia H, Sun J, et al. Quantity and apoptosis-related protein level of B lymphocyte in patients with immunorelated pancytopenia. Zhonghua Xue Ye Xue Za Zhi. 2002;23:236–8.PubMed
10.
go back to reference Fu R, Shao ZH, Liu H, He H, Sun J, Zhao MF, et al. Proliferation of bone marrow hematopoietic stem cells and function of T helper lymphocytes of patients with immuno-related pancytopenia. Zhonghua Xue Ye Xue Za Zhi. 2004;25:213–6.PubMed Fu R, Shao ZH, Liu H, He H, Sun J, Zhao MF, et al. Proliferation of bone marrow hematopoietic stem cells and function of T helper lymphocytes of patients with immuno-related pancytopenia. Zhonghua Xue Ye Xue Za Zhi. 2004;25:213–6.PubMed
11.
go back to reference Fu R, Wang HL, Chen J, Wang J, Li LJ, Liu H, et al. Study of the quantity and function of Th17 cells in the blood cytopenic patients with positive BMMNC-Coombs test. Zhonghua Xue Ye Xue Za Zhi. 2010;31:684–7.PubMed Fu R, Wang HL, Chen J, Wang J, Li LJ, Liu H, et al. Study of the quantity and function of Th17 cells in the blood cytopenic patients with positive BMMNC-Coombs test. Zhonghua Xue Ye Xue Za Zhi. 2010;31:684–7.PubMed
12.
go back to reference Fu R, Chen J, Wang HL, Wang J, Li LJ, Liu H, et al. Quantity and function of regulatory T cells in hemocytopenic patients with positive BMMNC-Coombs test. Zhonghua Yi Xue Za Zhi. 2010;90:2989–93.PubMed Fu R, Chen J, Wang HL, Wang J, Li LJ, Liu H, et al. Quantity and function of regulatory T cells in hemocytopenic patients with positive BMMNC-Coombs test. Zhonghua Yi Xue Za Zhi. 2010;90:2989–93.PubMed
13.
go back to reference Teng GS, Fu R, Liu H, Wang HL, Wang YH, Ruan EB, et al. Expression of CD80 and CD86 on dendritic cells of patients with immune related pancytopenia and its clinical significance. Zhonghua Xue Ye Xue Za Zhi. 2012;33:865–8.PubMed Teng GS, Fu R, Liu H, Wang HL, Wang YH, Ruan EB, et al. Expression of CD80 and CD86 on dendritic cells of patients with immune related pancytopenia and its clinical significance. Zhonghua Xue Ye Xue Za Zhi. 2012;33:865–8.PubMed
14.
go back to reference Teng GS, Fu R, Liu H, Wang HL, Wang YH, Ruan EB, et al. Quantity and subtypes of dendritic cells in patients with immune related pancytopenia and their clinical significance. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2012;20:722–6.PubMed Teng GS, Fu R, Liu H, Wang HL, Wang YH, Ruan EB, et al. Quantity and subtypes of dendritic cells in patients with immune related pancytopenia and their clinical significance. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2012;20:722–6.PubMed
15.
go back to reference Yu H, Fu R, Wang YH, Wang HQ, Liu H, Li LJ, et al. Preliminary study on the quantity and function of T follicular helper cells in the cytopenic patients with positive BMMNC-Coombs test. Zhonghua Xue Ye Xue Za Zhi. 2013;34:606–9.PubMed Yu H, Fu R, Wang YH, Wang HQ, Liu H, Li LJ, et al. Preliminary study on the quantity and function of T follicular helper cells in the cytopenic patients with positive BMMNC-Coombs test. Zhonghua Xue Ye Xue Za Zhi. 2013;34:606–9.PubMed
16.
go back to reference Yu H, Zhang J, Fu R, Liu H, Wang H, Ding K, et al. Increased frequency of bone marrow T follicular helper cells in patients with immune-related pancytopenia. Clin Dev Immunol. 2013;2013:730450.PubMedPubMedCentral Yu H, Zhang J, Fu R, Liu H, Wang H, Ding K, et al. Increased frequency of bone marrow T follicular helper cells in patients with immune-related pancytopenia. Clin Dev Immunol. 2013;2013:730450.PubMedPubMedCentral
17.
go back to reference Wang YH, Fu R, Shao ZH. A pilot study of memory B lymphocytes in relapsed immune-related pancytopenia patients. Clin Lab. 2014;60:729–33.PubMed Wang YH, Fu R, Shao ZH. A pilot study of memory B lymphocytes in relapsed immune-related pancytopenia patients. Clin Lab. 2014;60:729–33.PubMed
18.
go back to reference Wang YH, Fu R, Shao ZH, Wang HQ, Xing LM, Liu H, et al. Study on quantity and function of bone marrow macrophages in patients with BMMNC-Coombs Test(+) pancytopenia. Zhonghua Xue Ye Xue Za Zhi. 2009;30:538–42.PubMed Wang YH, Fu R, Shao ZH, Wang HQ, Xing LM, Liu H, et al. Study on quantity and function of bone marrow macrophages in patients with BMMNC-Coombs Test(+) pancytopenia. Zhonghua Xue Ye Xue Za Zhi. 2009;30:538–42.PubMed
19.
go back to reference Wang YH, Fu R, Shao ZH, Xing LM, Wang HQ, Wu YH, et al. Expression of bone marrow macrophages antigen activation and its clinical significance in pancytopenia patients with positive bone marrow mononuclear cells-Coombs test. Zhonghua Nei Ke Za Zhi. 2010;49:146–9.PubMed Wang YH, Fu R, Shao ZH, Xing LM, Wang HQ, Wu YH, et al. Expression of bone marrow macrophages antigen activation and its clinical significance in pancytopenia patients with positive bone marrow mononuclear cells-Coombs test. Zhonghua Nei Ke Za Zhi. 2010;49:146–9.PubMed
20.
go back to reference Chen J, Fu R, Li LJ, Liu H, Wang YH, Wang HL, et al. Variation in complement level and its significance in cytopenia patients with positive BMMNC-Coombs. Zhonghua Xue Ye Xue Za Zhi. 2009;30:454–7.PubMed Chen J, Fu R, Li LJ, Liu H, Wang YH, Wang HL, et al. Variation in complement level and its significance in cytopenia patients with positive BMMNC-Coombs. Zhonghua Xue Ye Xue Za Zhi. 2009;30:454–7.PubMed
21.
go back to reference Valent P, Horny HP, Bennett JM, Fonatsch C, Germing U, Greenberg P, et al. Definitions and standards in the diagnosis and treatment of the myelodysplastic syndromes: consensus statements and report from a working conference. Leuk Res. 2007;31:727–36.CrossRefPubMed Valent P, Horny HP, Bennett JM, Fonatsch C, Germing U, Greenberg P, et al. Definitions and standards in the diagnosis and treatment of the myelodysplastic syndromes: consensus statements and report from a working conference. Leuk Res. 2007;31:727–36.CrossRefPubMed
22.
go back to reference Malcovati L, Cazzola M. The shadowlands of MDS: idiopathic cytopenias of undetermined significance (ICUS) and clonal hematopoiesis of indeterminate potential (CHIP). Hematology Am Soc Hematol Educ Program. 2015;2015:299–307.PubMed Malcovati L, Cazzola M. The shadowlands of MDS: idiopathic cytopenias of undetermined significance (ICUS) and clonal hematopoiesis of indeterminate potential (CHIP). Hematology Am Soc Hematol Educ Program. 2015;2015:299–307.PubMed
23.
go back to reference Schroeder T, Ruf L, Bernhardt A, Hildebrandt B, Aivado M, Aul C, et al. Distinguishing myelodysplastic syndromes (MDS) from idiopathic cytopenia of undetermined significance (ICUS): HUMARA unravels clonality in a subgroup of patients. Ann Oncol. 2010;21:2267–71.CrossRefPubMed Schroeder T, Ruf L, Bernhardt A, Hildebrandt B, Aivado M, Aul C, et al. Distinguishing myelodysplastic syndromes (MDS) from idiopathic cytopenia of undetermined significance (ICUS): HUMARA unravels clonality in a subgroup of patients. Ann Oncol. 2010;21:2267–71.CrossRefPubMed
24.
go back to reference Fu R, Liu H, Wang Y, Liu H, He H, Chen J, et al. Distinguishing immunorelated haemocytopenia from idiopathic cytopenia of undetermined significance (ICUS): a bone marrow abnormality mediated by autoantibodies. Clin Exp Immunol. 2014;177:412–8.CrossRefPubMedPubMedCentral Fu R, Liu H, Wang Y, Liu H, He H, Chen J, et al. Distinguishing immunorelated haemocytopenia from idiopathic cytopenia of undetermined significance (ICUS): a bone marrow abnormality mediated by autoantibodies. Clin Exp Immunol. 2014;177:412–8.CrossRefPubMedPubMedCentral
25.
go back to reference Krebs P, Kurrer M, Sahin U, Tureci O, Ludewig B. Autoimmunity seen through the SEREX-scope. Autoimmun Rev. 2003;2:339–45.CrossRefPubMed Krebs P, Kurrer M, Sahin U, Tureci O, Ludewig B. Autoimmunity seen through the SEREX-scope. Autoimmun Rev. 2003;2:339–45.CrossRefPubMed
26.
go back to reference Lozzio BB, Lozzio CB, Bamberger EG, Feliu AS. A multipotential leukemia cell line (K-562) of human origin. Proc Soc Exp Biol Med. 1981;166:546–50.CrossRefPubMed Lozzio BB, Lozzio CB, Bamberger EG, Feliu AS. A multipotential leukemia cell line (K-562) of human origin. Proc Soc Exp Biol Med. 1981;166:546–50.CrossRefPubMed
27.
go back to reference Shao ZH, Fu R. Immuno-related pancytopenia: a newly identified disease. Natl Med J China. 2005;40:5–9. Shao ZH, Fu R. Immuno-related pancytopenia: a newly identified disease. Natl Med J China. 2005;40:5–9.
28.
go back to reference Schagger H, Brandt U, Gencic S, von Jagow G. Ubiquinol-cytochrome-c reductase from human and bovine mitochondria. Methods Enzymol. 1995;260:82–96.CrossRefPubMed Schagger H, Brandt U, Gencic S, von Jagow G. Ubiquinol-cytochrome-c reductase from human and bovine mitochondria. Methods Enzymol. 1995;260:82–96.CrossRefPubMed
29.
go back to reference Meunier B, Fisher N, Ransac S, Mazat JP, Brasseur G. Respiratory complex III dysfunction in humans and the use of yeast as a model organism to study mitochondrial myopathy and associated diseases. Biochim Biophys Acta. 2013;1827:1346–61.CrossRefPubMed Meunier B, Fisher N, Ransac S, Mazat JP, Brasseur G. Respiratory complex III dysfunction in humans and the use of yeast as a model organism to study mitochondrial myopathy and associated diseases. Biochim Biophys Acta. 2013;1827:1346–61.CrossRefPubMed
30.
go back to reference Shichijo K, Mitsui T, Kunishige M, Kuroda Y, Masuda K, Matsumoto T. Involvement of mitochondria in myasthenia gravis complicated with dermatomyositis and rheumatoid arthritis: a case report. Acta Neuropathol. 2005;109:539–42.CrossRefPubMed Shichijo K, Mitsui T, Kunishige M, Kuroda Y, Masuda K, Matsumoto T. Involvement of mitochondria in myasthenia gravis complicated with dermatomyositis and rheumatoid arthritis: a case report. Acta Neuropathol. 2005;109:539–42.CrossRefPubMed
31.
go back to reference Li X, Fang P, Mai J, Choi ET, Wang H, Yang XF. Targeting mitochondrial reactive oxygen species as novel therapy for inflammatory diseases and cancers. J Hematol Oncol. 2013;6:19.CrossRefPubMedPubMedCentral Li X, Fang P, Mai J, Choi ET, Wang H, Yang XF. Targeting mitochondrial reactive oxygen species as novel therapy for inflammatory diseases and cancers. J Hematol Oncol. 2013;6:19.CrossRefPubMedPubMedCentral
32.
go back to reference Sena LA, Li S, Jairaman A, Prakriya M, Ezponda T, Hildeman DA, et al. Mitochondria are required for antigen-specific T cell activation through reactive oxygen species signaling. Immunity. 2013;38:225–36.CrossRefPubMedPubMedCentral Sena LA, Li S, Jairaman A, Prakriya M, Ezponda T, Hildeman DA, et al. Mitochondria are required for antigen-specific T cell activation through reactive oxygen species signaling. Immunity. 2013;38:225–36.CrossRefPubMedPubMedCentral
33.
go back to reference Pazmandi K, Agod Z, Kumar BV, Szabo A, Fekete T, Sogor V, et al. Oxidative modification enhances the immunostimulatory effects of extracellular mitochondrial DNA on plasmacytoid dendritic cells. Free Radic Biol Med. 2014;77:281–90.CrossRefPubMed Pazmandi K, Agod Z, Kumar BV, Szabo A, Fekete T, Sogor V, et al. Oxidative modification enhances the immunostimulatory effects of extracellular mitochondrial DNA on plasmacytoid dendritic cells. Free Radic Biol Med. 2014;77:281–90.CrossRefPubMed
Metadata
Title
Screening novel autoantigens targeted by serum IgG autoantibodies in immunorelated pancytopenia by SEREX
Authors
Shanfeng Hao
Rong Fu
Huaquan Wang
Zonghong Shao
Publication date
01-11-2017
Publisher
Springer Japan
Published in
International Journal of Hematology / Issue 5/2017
Print ISSN: 0925-5710
Electronic ISSN: 1865-3774
DOI
https://doi.org/10.1007/s12185-017-2287-0

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