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Antiendothelial cell antibodies as the tip of the iceberg: What is hidden underneath?

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Abstract

A system analysis of the published data on antiendothelial cell antibodies (AECAs) was performed. The AECAs target antigens on endothelial cells are characterized, the methodology of revealing AECAs is described, and the role of antibodies in the pathogenesis of processes caused by the activation/dysfunction of endothelium is considered. The review summarizes the present-day results of Russian and international studies published in the last 25 years in the Pubmed, High Wire, and e-Library databases. The characteristics of natural and disease-associated AECAs (related to pathology) and mechanisms of their influence on cells in different pathologies are presented.

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References

  • Aird, W.C., Endothelium in health and disease, Pharmacol. Rep., 2008, vol. 60, no. 1, pp. 139–143.

    PubMed  Google Scholar 

  • Alessandri, C., Bombardieri, M., and Valesini, G., Pathogenic mechanisms of anti-endothelial cell antibodies (AECA): their prevalence and clinical relevance, Adv. Clin. Chem., 2006, vol. 42, pp. 297–326.

    Article  PubMed  Google Scholar 

  • Al Mahri, A., Holgersson, J., and Alheim, M., Detection of complement-fixing and non-fixing antibodies specific for endothelial precursor cells and lymphocytes using flow cytometry, Tissue Antigens, 2012, vol. 80, no. 5, pp. 404–415.

    Article  Google Scholar 

  • Baranska, P., Jerczynska, H., Pawlowska, Z., et al., Expression of integrins and adhesive properties of human endothelial cell line EA.hy 926, Cancer Genomics Proteomics, 2005, vol. 2, no. 5, pp. 3–7.

    Google Scholar 

  • Belizna, C., Duijvestijn, A., Hamidou, M., and Tervaert, J.W., Antiendothelial cell antibodies in vasculitis and con nective tissue disease, Ann. Rheum. Dis., 2006, vol. 65, no. 12, pp. 1545–1550.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bordron, A., Révélen, R., D’Arbonneau, F., et al., Functional heterogeneity of anti-endothelial antibodies, Clin. Exp. Immunol., 2001, vol. 124, no. 3, pp. 492–501.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Carvalho, D., Savage, C.O., Isenberg, D., and Pearson, J.D., IgG antiendothelial cell antibodies from patients with systemic lupus erythematosus or systemic vasculitis stimulate the release of two endothelial cell-derived mediators, which enhance adhesion molecule expression and leukocyte adhesion in a autocrine manner, Arthritis Rheum., 1999, vol. 42, no. 4, pp. 631–640.

    Article  CAS  PubMed  Google Scholar 

  • Cieslik, P., Hrycek, A., and Klucinski, P., Vasculopathy and vasculitis in systemic lupus erythematosus, Pol. Arch. Med. Wewn., 2008, vol. 118, nos. 1–2, pp. 57–63.

    PubMed  Google Scholar 

  • Cines, D.B., Pollak, E.S., Buck, C.A., et al., Endothelial cells in physiology and in the pathophysiology of vascular disorders, Blood, 1998, vol. 91, no. 10, pp. 3527–3561.

    CAS  PubMed  Google Scholar 

  • Constans, J., Dupuy, R., Blann, A.D., et al., Anti-endothelial cell antibodies and soluble markers of endothelial cell dysfunction in systemic lupus erythematosus, J. Rheumatol., 2003, vol. 30, no. 9, pp. 1963–1966.

    CAS  PubMed  Google Scholar 

  • Dib, H., Tamby, M.C., Bussone, G., et al., Targets of antiendothelial cell antibodies in pulmonary hypertension and scleroderma, Eur. Respir. J., 2012, vol. 39, no. 6, pp. 1405–1414.

    Article  CAS  PubMed  Google Scholar 

  • Dieude, M., Senecal, J.L., and Raymond, Y., Induction of endothelial cell apoptosis by heat-shock protein 60-reactive antibodies from anti-endothelial cell autoantibody— positive systemic lupus erythematosus patients, Arthritis Rheum., 2004, vol. 50, no. 10, pp. 3221–3231.

    Article  CAS  PubMed  Google Scholar 

  • Drouet, C., Nissou, M.F., Ponard, D., et al., Detection of antiendothelial cell antibodies by an enzyme-linked immunosorbent assay using antigens from cell lysate: minimal interference with antinuclear antibodies and rheumatoid factors, Clin. Diagn. Lab. Immunol., 2003, vol. 10, no. 5, pp. 934–939.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Duval, A., Helley, D., Capron, L., et al., Endothelial dysfunction in systemic lupus patients with low disease activity: evaluation by quantification and characterization of circulating endothelial microparticles, role of anti-endothelial cell antibodies, Rheumatology, 2010, vol. 49, no. 6, pp. 1049–1055.

    Article  CAS  PubMed  Google Scholar 

  • Edgell, C.J., McDonald, C.C., and Graham, J.B., Permanent cell line expressing human factor VIII-related antigen established by hybridization, Proc. Natl. Acad. Sci. U.S.A., 1983, vol. 80, no. 12, pp. 3734–3737.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Florey, O.J., Johns, M., Esho, O.O., et al., Antiendothelial cell antibodies mediate enhanced leukocyte adhesion to cytokine-activated endothelial cells through a novel mechanism requiring cooperation between FcγRIIa and CXCR1/2, Blood, 2007, vol. 109, no. 9, pp. 3881–3889.

    Article  CAS  PubMed  Google Scholar 

  • Frolova, L.A., Frolov, A.K., Fushtei, I.M., et al., Analysis of the dynamics of humoral immunity factors in the blood plasma of women in different periods of ontogenesis, Immunopatol., Allergol., Infektol., 2013, no. 2, pp. 20–24.

    Google Scholar 

  • Gomazkov, O.A., Endothelium—“endocrine tree,” Priroda (Moscow), 2000, no. 5, pp. 5–7.

    Google Scholar 

  • Graham, A., Ford, I, Morrison, R., et al., Anti-endothelial cell antibodies interfere in apoptotic cell clearance and promote thrombosis in patients with antiphospholipid syndrome, J. Immunol., 2009, vol. 182, no. 3, pp. 1756–1762.

    Article  CAS  PubMed  Google Scholar 

  • Guilpain, P. and Mouthon, L., Antiendothelial cells autoantibodies in vasculitis-associated systemic diseases, Clin. Rev. Allergy Immunol., 2008, vol. 35, nos. 1–2, pp. 59–65.

    Article  CAS  PubMed  Google Scholar 

  • Holmen, C., Elsheikh, E., Christensson, M., et al., Antiendothelial cell antibodies selectively activate SAPK/JNK signaling in Wegener’s granulomatosis, J. Am. Soc. Nephrol., 2007, vol. 18, no. 9, pp. 2497–2508.

    Article  CAS  PubMed  Google Scholar 

  • Horvathova, M., Jahnova, E., and Nyulassy, S., Detection of antiendothelial cell antibodies in patients with connective tissue diseases by flow cytometry and their relation to endothelial cell activation, Physiol. Res., 2002, vol. 51, no. 6, pp. 613–617.

    CAS  PubMed  Google Scholar 

  • Jackson, A.M., Lucas, D.P., Melancon, J.K., and Desai, N.M., Clinical relevance and IgG subclass determination of non-HLA antibodies identified using endothelial cell precursors isolated from donor blood, Transplantation, 2011, vol. 92, pp. 54–60.

    Article  CAS  PubMed  Google Scholar 

  • Jackson, A.M., Sigdel, T.K., Delville, M., et al., Endothelial cell antibodies associated with novel targets and increased rejection, J. Am. Soc. Nephrol., 2015, vol. 26, no. 5, pp. 1161–1171.

    Article  CAS  PubMed  Google Scholar 

  • Karasawa, R., Fujieda, M., Ohta, K., and Yudoh, K., Validation of a new biomarker in patients with Kawasaki disease identified by proteomics, J. Data Min. Genomics Proteomics, 2013, vol. 4, pp. 1–3.

    Google Scholar 

  • Kimura, A., Yoshikura, N., Koumura, A., et al., Identification of target antigens of naturally occurring autoantibodies in cerebrospinal fluid, J. Proteomics, 2015, vol. 128, pp. 450–457.

    Article  CAS  PubMed  Google Scholar 

  • King, A., Boocock, C., Sharkey, A.M., et al., Evidence for the expression of HLA-C class I mRNA and protein by human first trimester trophoblast, J. Immunol., 1996, vol. 156, no. 6, pp. 2068–2076.

    CAS  PubMed  Google Scholar 

  • Kornberg, A., Renaudineau, Y., Blank, M., et al., Antibeta2- glycoprotein I antibodies induce tissue factor in endothelial cells, Isr. Med. Assoc. J., 2000, vol. 2, pp. 27–31.

    PubMed  Google Scholar 

  • Lewandowska, K., Ciurzynski, M., Gorska, E., et al., Antiendothelial cell antibodies in patients with systemic sclerosis in relation to pulmonary hypertension and lung fibrosis, Adv. Exp. Med. Biol., 2013, vol. 756, pp. 147–153.

    Article  CAS  PubMed  Google Scholar 

  • Li, M.T., Tian, Z., Fang, Q., et al., Prevalence of antiendothelial cell antibodies in patients with pulmonary arterial hypertension associated with connective tissue diseases, Chin. Med. Sci. J., 2010, vol. 25, no. 1, pp. 27–31.

    Article  PubMed  Google Scholar 

  • Lindqvist, K.J. and Osterland, C.K., Human antibodies to vascular endothelium, Clin. Exp. Immunol., 1971, vol. 9, no. 6, pp. 753–760.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Magro, C.M., Poe, J.C., Lubow, M., and Susac, J.O., Susac syndrome: an organ-specific autoimmune endotheliopathy syndrome associated with anti-endothelial cell antibodies, Am. J. Clin. Pathol., 2011, vol. 136, no. 6, pp. 903–912.

    Article  CAS  PubMed  Google Scholar 

  • Mendonca, L.L., Khamashta, M.A., Cuadrado, M.J., et al., Natural immune response involving anti-endothelial cell antibodies in normal and lupus pregnancy, Arthritis Rheum., 2000, vol. 43, no. 7, pp. 1511–1515.

    Article  CAS  PubMed  Google Scholar 

  • Meroni, P., Ronda, N., Raschi, E., and Borghi, M.O., Humoral autoimmunity against endothelium: theory or reality? Trends Immunol., 2005, vol. 26, no. 5, pp. 275–281.

    Article  CAS  PubMed  Google Scholar 

  • Perricone, C., Pendolino, M., Olivieri, M., et al., Neuropsychiatric manifestations associated with anti-endothelial cell antibodies in systemic lupus erythematosus, Isr. Med. Assoc. J., 2015, vol. 17, no. 3, pp. 171–178.

    PubMed  Google Scholar 

  • Praprotnik, S., Blank, M., Levy, Y., Tavor, S., et al., Antiendothelial cell antibodies from patients with thrombotic thrombocytopenic purpura specifically activate small vessel endothelial cells, Int. Immunol., 2001a, vol. 13, no. 2, pp. 203–210.

    Google Scholar 

  • Praprotnik, S., Blank, M., Meroni, P.L., Rozman, B., Eldor, A., and Shoenfeld, Y., Classification of antiendothelial cell antibodies into antibodies against microvascular and macrovascular endothelial cells: the pathogenic and diagnostic implications, Arthritis Rheum., 2001b, vol. 44, pp. 1484–1494.

    Google Scholar 

  • Rappaport, V.J., Hirata, G., Yap, H.K., and Jordan, S.C., Anti-vascular endothelial cell antibodies in severe preeclampsia, Am. J. Obstet. Gynecol., 1990, vol. 162, no. 1, pp. 138–146.

    Article  CAS  PubMed  Google Scholar 

  • Regent, A., Dib, H., Ly, K.H., et al., Identification of target antigens of anti-endothelial cell and anti-vascular smooth muscle cell antibodies in patients with giant cell arteritis: a proteomic approach, Arthritis Res. Ther., 2011, vol. 13, no. 3, p. R107.

    Google Scholar 

  • Renaudineau, Y., Revelen, R., Bordron, A., et al., Two populations of endothelial cell antibodies cross-react with heparin, Lupus, 1998, vol. 7, no. 2, pp. 86–94.

    Article  CAS  PubMed  Google Scholar 

  • Ronda, N., Bernini, F., Giacosa, R., et al., Normal human IgG prevents endothelial cell activation induced by TNFalpha and oxidized low-density lipoprotein atherogenic stimuli, Clin. Exp. Immunol., 2003, vol. 133, no. 2, pp. 219–226.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Roussev, R.G., Stern, J.J., Kaider, B.D., and Thaler, C.J., Anti-endothelial cell antibodies: another cause for pregnancy loss? Am. J. Reprod. Immunol., 1998, vol. 39, no. 2, pp. 89–95.

    Article  CAS  PubMed  Google Scholar 

  • Servettaz, A., Guilpain, P., Camoin, L., et al., Identification of target antigens of anti-endothelial cell antibodies in healthy individuals. A proteomic approach, Proteomics, 2008a, vol. 8, no. 5, pp. 1000–1008.

    Google Scholar 

  • Servettaz, A., Guilpain, P., Tamas, N., et al., Natural antiendothelial cell antibodies, Autoimmun. Rev., 2008b, vol. 7, no. 6, pp. 426–430.

    Google Scholar 

  • Shirai, T., Fuji, H., Ono, M., et al., An innovative method to identify autoantigens expressed on the cell surface: Serological Identification System for Autoantigens Using a Retroviral Vector and Flow Cytometry (SARF), Clin. Dev. Immunol., 2013, vol. 2013, pp. 1–10.

    Article  Google Scholar 

  • Tamby, M.C., Chanseaud, Y., Humbert, M., et al., Antiendothelial cell antibodies in idiopathic and systemic sclerosis associated pulmonary arterial hypertension, Thorax, 2005, vol. 60, no. 9, pp. 765–772.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tseng, J.C., Lu, L.Y., Hu, R.J., et al., Elevated serum antiendothelial cell autoantibodies titer is associated with lupus nephritis in patients with systemic lupus erythematosus, J. Microbiol. Immun. Infect., 2007, vol. 40, no. 1, pp. 50–55.

    CAS  Google Scholar 

  • Urlacher, A., Tongio, M.M., and Pasquali, J.L., IgM antiidiotypes that block anti-HLA antibodies: naturally occurring or immune antibodies? Clin. Exp. Immunol., 1991, vol. 83, no. 1, pp. 116–120.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Varela, C., de Haro, J., Bleda, S., et al., Anti-endothelial cell antibodies are associated with peripheral arterial disease and markers of endothelial dysfunction and inflammation, Interact. Cardiovasc. Thorac. Surg., 2011, vol. 13, no. 5, pp. 463–467.

    Article  PubMed  Google Scholar 

  • Wigley, F.M., Vascular disease in scleroderma, Clin. Rev. Allergy Immunol., 2009, vol. 36, nos. 2–3, pp. 150–175.

    Article  PubMed  Google Scholar 

  • Yamamoto, T., Takahashi, Y., Kuno, S., et al., Effects of anti-endothelial cell antibody in pre-eclampsia on endothelin-1 release from cultured endothelial cells, Immunol. Cell. Biol., 1997, vol. 75, no. 4, pp. 340–344.

    Article  CAS  PubMed  Google Scholar 

  • Yamamoto, T., Geshi, Y., Kuno, S., et al., Anti-endothelial cell antibody in preeclampsia: clinical findings and serum cytotoxity to endothelial cell, Jpn. J. Clin. Immunol., 1998, vol. 21, no. 5, pp. 191–197.

    Article  CAS  Google Scholar 

  • Youinou, P., New target antigens for antiendothelial cell antibodies, Immunobiology, 2005, vol. 210, no. 10, pp. 789–797.

    Article  CAS  PubMed  Google Scholar 

  • Ziganshina, M.M., Bovin, N.V., and Sukhikh, G.T., Natural antibodies as a key element of the mechanism supporting homeostasis in the immune system, Immunologiya, 2013a, vol. 34, no. 5, pp. 277–282.

    Google Scholar 

  • Ziganshina, M.M., Pavlovich, S.V., Bovin, N.V., and Sukhikh, G.T., Humoral rejection in the obstetrical pathology, Akush. Ginekol. (Moscow), 2013b, no. 6, pp. 3–10.

    Google Scholar 

  • Ziganshina, M.M., Nikolaeva, M.A., Stepanova, E.O., et al., Detection of antibodies in vitro binding to endothelial cells in the women with normal pregnancy and preeclampsia, Bull. Exp. Biol. Med., 2015, vol. 159, no. 4, pp. 475–478.

    Article  CAS  PubMed  Google Scholar 

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Correspondence to M. M. Ziganshina.

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Original Russian Text © M.M. Ziganshina, O.A. Sergunina, M.A. Nikolaeva, G.T. Sukhikh, 2017, published in Uspekhi Sovremennoi Biologii, 2017, Vol. 137, No. 3, pp. 288–299.

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Ziganshina, M.M., Sergunina, O.A., Nikolaeva, M.A. et al. Antiendothelial cell antibodies as the tip of the iceberg: What is hidden underneath?. Biol Bull Rev 7, 537–546 (2017). https://doi.org/10.1134/S207908641706010X

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  • DOI: https://doi.org/10.1134/S207908641706010X

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