Annexin A2 As a Target Endothelial Cell Membrane Autoantigen in Behçet's Disease

Overview

Journal Sci Rep

Specialty Science

Date 2015 Feb 3

PMID 25641213

Citations 10

Authors

Peng Chen

Hai Yan

Yaping Tian

Yiping Xun

Lili Shi

Ran Bao

Huai Zhang

Guangyu Chen

Chunhe Yang

Shutao Sun

Yajie Wang

Li Liu

Yabin Zhou

Chunyan Zhang

Xiaoxu Wang

Yongqiang Wen

Yongzhong Bian

Hongwu Du

Affiliations

Soon will be listed here.

Abstract

Cell membrane proteins are believed to play a critical role in the pathogenesis of autoimmune diseases. However, few membrane autoantigens have been linked with Behçet's disease. Here, a cell-chip was performed to identify autoantibody target cells, and the suspected autoantigens were detected using immunoblotting. The amino acid sequences of the detected proteins were determined using LC-MALDI-TOF/TOF. Putative proteins were recombinantly expressed and purified, and a corresponding ELISA was developed and clinically validated using real clinical samples. It was found that a 36-kDa membrane protein--annexin A2--was detected in approximately one-third of the patients' blood circulation. The immunohistochemistry results showed that annexin A2 was highly expressed in vascular endothelial cells. Moreover, vascular involvement was significantly higher in the anti-annexin A2 antibody-positive group versus the anti-annexin A2 antibody-negative group among all the clinical samples analyzed, indicating that annexin A2 is a novel endothelial cell membrane antigen involved in Behçet's disease.

Citing Articles

Annexin A2: A Double-Edged Sword in Pathogen Infection.

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Shimizu J, Murayama M, Mizukami Y, Arimitsu N, Takai K, Miyabe Y Front Med (Lausanne). 2023; 10:1055753.

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The important roles and molecular mechanisms of annexin A autoantibody in children with nephrotic syndrome.

Ye Q, Zhang Y, Zhuang J, Bi Y, Xu H, Shen Q Ann Transl Med. 2021; 9(18):1452.

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References

. Criteria for diagnosis of Behçet's disease. International Study Group for Behçet's Disease. Lancet. 1990; 335(8697):1078-80. View

Swisher J, Khatri U, Feldman G . Annexin A2 is a soluble mediator of macrophage activation. J Leukoc Biol. 2007; 82(5):1174-84. DOI: 10.1189/jlb.0307154. View

Fang Y, Lin C, Liao P, Kuo Y, Wang S, Yeh T . Annexin A2 on lung epithelial cell surface is recognized by severe acute respiratory syndrome-associated coronavirus spike domain 2 antibodies. Mol Immunol. 2009; 47(5):1000-9. PMC: 7112629. DOI: 10.1016/j.molimm.2009.11.019. View

Backes P, Quinkert D, Reiss S, Binder M, Zayas M, Rescher U . Role of annexin A2 in the production of infectious hepatitis C virus particles. J Virol. 2010; 84(11):5775-89. PMC: 2876593. DOI: 10.1128/JVI.02343-09. View

Birtas-Atesoglu E, Inanc N, Yavuz S, Ergun T, Direskeneli H . Serum levels of free heat shock protein 70 and anti-HSP70 are elevated in Behçet's disease. Clin Exp Rheumatol. 2008; 26(4 Suppl 50):S96-8. View

Cho S, Ahn K, Kim D, Zheng Z, Cho S, Kang S . Identification of HnRNP-A2/B1 as a target antigen of anti-endothelial cell IgA antibody in Behçet's disease. J Invest Dermatol. 2011; 132(3 Pt 1):601-8. DOI: 10.1038/jid.2011.397. View

Iaccarino L, Ghirardello A, Canova M, Zen M, Bettio S, Nalotto L . Anti-annexins autoantibodies: their role as biomarkers of autoimmune diseases. Autoimmun Rev. 2011; 10(9):553-8. DOI: 10.1016/j.autrev.2011.04.007. View

Res P, Schaar C, Breedveld F, van Eden W, van Embden J, Cohen I . Synovial fluid T cell reactivity against 65 kD heat shock protein of mycobacteria in early chronic arthritis. Lancet. 1988; 2(8609):478-80. DOI: 10.1016/s0140-6736(88)90123-7. View

Delunardo F, Conti F, Margutti P, Alessandri C, Priori R, Siracusano A . Identification and characterization of the carboxy-terminal region of Sip-1, a novel autoantigen in Behçet's disease. Arthritis Res Ther. 2006; 8(3):R71. PMC: 1526626. DOI: 10.1186/ar1940. View

10.

Lokman N, Ween M, Oehler M, Ricciardelli C . The role of annexin A2 in tumorigenesis and cancer progression. Cancer Microenviron. 2011; 4(2):199-208. PMC: 3170418. DOI: 10.1007/s12307-011-0064-9. View

11.

Mor F, Weinberger A, Cohen I . Identification of alpha-tropomyosin as a target self-antigen in Behçet's syndrome. Eur J Immunol. 2002; 32(2):356-65. DOI: 10.1002/1521-4141(200202)32:2<356::AID-IMMU356>3.0.CO;2-9. View

12.

Lehner T, Lavery E, Smith R, van der Zee R, Mizushima Y, Shinnick T . Association between the 65-kilodalton heat shock protein, Streptococcus sanguis, and the corresponding antibodies in Behçet's syndrome. Infect Immun. 1991; 59(4):1434-41. PMC: 257860. DOI: 10.1128/iai.59.4.1434-1441.1991. View

13.

Salle V, Maziere J, Smail A, Cevallos R, Maziere C, Fuentes V . Anti-annexin II antibodies in systemic autoimmune diseases and antiphospholipid syndrome. J Clin Immunol. 2008; 28(4):291-7. DOI: 10.1007/s10875-008-9188-1. View

14.

Sun C, Zhang H, Li J, Huang H, Cheng H, Wang Y . Modulation of the major histocompatibility complex by neural stem cell-derived neurotrophic factors used for regenerative therapy in a rat model of stroke. J Transl Med. 2010; 8:77. PMC: 2936305. DOI: 10.1186/1479-5876-8-77. View

15.

Vural B, Sehitoglu E, Cavus F, Yalcinkaya N, Haytural H, Kucukerden M . Mitochondrial carrier homolog 1 (Mtch1) antibodies in neuro-Behçet's disease. J Neuroimmunol. 2013; 263(1-2):139-44. DOI: 10.1016/j.jneuroim.2013.08.007. View

16.

Xun Y, Chen P, Yan H, Yang W, Shi L, Chen G . Identification of prohibitin as an antigen in Behcet's disease. Biochem Biophys Res Commun. 2014; 451(3):389-93. DOI: 10.1016/j.bbrc.2014.07.126. View

17.

Lu Y, Ye P, Chen S, Tan E, Chan E . Identification of kinectin as a novel Behçet's disease autoantigen. Arthritis Res Ther. 2005; 7(5):R1133-9. PMC: 1257442. DOI: 10.1186/ar1798. View

18.

Zhang C, Bai N, Chang A, Zhang Z, Yin J, Shen W . ATF4 is directly recruited by TLR4 signaling and positively regulates TLR4-trigged cytokine production in human monocytes. Cell Mol Immunol. 2012; 10(1):84-94. PMC: 4003182. DOI: 10.1038/cmi.2012.57. View

19.

Verity D, Marr J, Ohno S, Wallace G, Stanford M . Behçet's disease, the Silk Road and HLA-B51: historical and geographical perspectives. Tissue Antigens. 1999; 54(3):213-20. DOI: 10.1034/j.1399-0039.1999.540301.x. View

20.

Du H, Chen G, Wang S, Wang S, Li S, Li C . Immunological screening and characterization of highly specific monoclonal antibodies against 20 kDa hGH. Bioanalysis. 2012; 4(17):2161-8. DOI: 10.4155/bio.12.188. View