title: An innovative method to identify autoantigens expressed on the endothelial cell surface: serological identification system for autoantigens using a retroviral vector and flow cytometry (SARF).
abstract: Autoantibodies against integral membrane proteins are usually pathogenic. Although anti-endothelial cell antibodies (AECAs) are considered to be critical, especially for vascular lesions in collagen diseases, most molecules identified as autoantigens for AECAs are localized within the cell and not expressed on the cell surface. For identification of autoantigens, proteomics and expression library analyses have been performed for many years with some success. To specifically target cell-surface molecules in identification of autoantigens, we constructed a serological identification system for autoantigens using a retroviral vector and flow cytometry (SARF). Here, we present an overview of recent research in AECAs and their target molecules and discuss the principle and the application of SARF. Using SARF, we successfully identified three different membrane proteins: fibronectin leucine-rich transmembrane protein 2 (FLRT2) from patients with systemic lupus erythematosus (SLE), intercellular adhesion molecule 1 (ICAM-1) from a patient with rheumatoid arthritis, and Pk (Gb3/CD77) from an SLE patient with hemolytic anemia, as targets for AECAs. SARF is useful for specific identification of autoantigens expressed on the cell surface, and identification of such interactions of the cell-surface autoantigens and pathogenic autoantibodies may enable the development of more specific intervention strategies in autoimmune diseases.
authors: Department of Hematology and Rheumatology, Tohoku University Graduate School of Medicine, Sendai, Miyagi 980-8574, Japan.
authors: Tsuyoshi
authors: T
authors: Shirai
authors: Hiroshi
authors: H
authors: Fujii
authors: Masao
authors: M
authors: Ono
authors: Ryu
authors: R
authors: Watanabe
authors: Tomonori
authors: T
authors: Ishii
authors: Hideo
authors: H
authors: Harigae
mesh_terms: D000743:Anemia, Hemolytic / Q000150:complications / Q000175:diagnosis* / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000175:diagnosis* / Q000276:immunology; D001324:Autoantigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D002469:Cell Separation; D004847:Epithelial Cells / Q000276:immunology*; D005434:Flow Cytometry; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000150:complications / Q000175:diagnosis* / Q000276:immunology; D040901:Proteomics; D012190:Retroviridae / Q000235:genetics*; D012699:Serology / Q000379:methods* / Q000639:trends
chemical_list: D001324:Autoantigens
references: Arthritis Rheum. 2004 Oct;50(10):3221-31
references: 15476243
references: Blood. 2008 May 1;111(9):4559-70
references: 17993611
references: Arthritis Rheum. 2006 Jul;54(7):2326-33
references: 16802373
references: Int Immunol. 2001 Feb;13(2):203-10
references: 11157853
references: Clin Rev Allergy Immunol. 2008 Oct;35(1-2):59-65
references: 18228162
references: Clin Rev Allergy Immunol. 1997 Spring;15(1):41-52
references: 9209800
references: Br J Haematol. 1997 Apr;97(1):227-32
references: 9136970
references: Ann Rheum Dis. 2010 Feb;69(2):319-24
references: 20107031
references: J Interferon Cytokine Res. 1995 Sep;15(9):819-25
references: 8536111
references: Arthritis Res Ther. 2012 Jul 02;14(4):R157
references: 22747982
references: J Immunol. 1986 Sep 1;137(5):1532-7
references: 3745915
references: Kidney Int. 2004 May;65(5):1564-7
references: 15086893
references: Microbiol Immunol. 2004;48(9):703-11
references: 15383707
references: Clin Exp Immunol. 1997 Jan;107(1):120-6
references: 9010266
references: J Immunol. 1996 Jun 15;156(12):4946-51
references: 8648146
references: J Immunol. 1999 Mar 1;162(5):2990-6
references: 10072550
references: Lancet. 1988 Jul 23;2(8604):183-6
references: 2899661
references: Immunobiology. 2005;210(10):789-97
references: 16325499
references: Arthritis Rheum. 2006 Jul;54(7):2250-62
references: 16802364
references: J Immunol. 1996 Dec 1;157(11):5097-103
references: 8943419
references: Nephron. 1994;66(1):21-8
references: 8107950
references: Arthritis Rheum. 2005 Dec;52(12):4028-38
references: 16320351
references: Biochem Biophys Res Commun. 1998 Sep 29;250(3):694-8
references: 9784408
references: Autoimmunity. 2001 May;33(3):171-9
references: 11683377
references: Glycoconj J. 1992 Dec;9(6):325-9
references: 1305424
references: Infect Immun. 1998 Sep;66(9):4355-66
references: 9712788
references: Transplantation. 2005 Jul 27;80(2):264-71
references: 16041273
references: Clin Rev Allergy. 1994 Fall;12(3):275-86
references: 7804959
references: Genomics. 1999 Dec 15;62(3):417-26
references: 10644439
references: Transpl Immunol. 1997 Jun;5(2):104-11
references: 9269032
references: J Rheumatol. 2001 Apr;28(4):805-8
references: 11327255
references: Aust N Z J Med. 1992 Dec;22(6):652-9
references: 1489288
references: Clin Immunol. 2006 Aug;120(2):212-9
references: 16580263
references: J Biol Chem. 2000 Jun 2;275(22):16723-9
references: 10747952
references: Arthritis Rheum. 1996 May;39(5):758-66
references: 8639172
references: J Biol Chem. 1994 Apr 29;269(17):12536-40
references: 7909803
references: Autoimmun Rev. 2010 Mar;9(5):A259-66
references: 19963079
references: Blood. 2011 Jan 13;117(2):678-87
references: 20971946
references: Clin Immunol. 2004 Jun;111(3):241-51
references: 15183145
references: Clin Exp Immunol. 1971 Dec;9(6):753-60
references: 4945736
references: Arthritis Rheum. 2001 Jul;44(7):1484-94
references: 11465698
references: Autoimmun Rev. 2002 Dec;1(6):365-72
references: 12848993
references: Gene Ther. 2000 Jun;7(12):1063-6
references: 10871756
references: Am J Clin Pathol. 2011 Dec;136(6):903-12
references: 22095376
references: Arthritis Rheum. 2000 Nov;43(11):2550-62
references: 11083280
references: Int J Cardiol. 2008 Nov 28;130(3):405-8
references: 18234377
references: Clin Immunol Immunopathol. 1994 Mar;70(3):206-10
references: 8313657
references: Adv Exp Med Biol. 2013;756:147-53
references: 22836630
references: Arthritis Rheum. 1998 Oct;41(10):1738-47
references: 9778215
references: Annu Rev Immunol. 1993;11:79-104
references: 8476578
references: Chest. 2010 Dec;138(6):1303-8
references: 20576735
references: Autoimmun Rev. 2008 Jun;7(6):426-30
references: 18558356
references: Am J Pathol. 1992 Sep;141(3):673-83
references: 1519671
references: Arthritis Rheum. 2003 Jul;48(7):2025-35
references: 12847697
references: Scand Cardiovasc J. 2010 Oct;44(5):255-9
references: 20528242
references: APMIS. 1993 Jan;101(1):91-4
references: 8457331
references: Arthritis Rheum. 1997 May;40(5):849-53
references: 9153545
references: J Autoimmun. 1999 Aug;13(1):121-7
references: 10441176
references: Expert Opin Biol Ther. 2011 Jan;11(1):77-87
references: 21133816
references: Proc Natl Acad Sci U S A. 2011 Jun 21;108(25):10255-9
references: 21646518
references: PLoS One. 2011 Feb 07;6(2):e14654
references: 21326874
references: Respir Med. 2008 Jan;102(1):128-33
references: 17851060
references: N Engl J Med. 2001 Aug 2;345(5):340-50
references: 11484692
references: Cardiovasc Res. 2001 Jun;50(3):547-55
references: 11376630
references: Clin Exp Immunol. 2010 Sep;161(3):459-70
references: 20646000
references: J Immunol. 2000 Sep 15;165(6):3375-83
references: 10975856
references: J Clin Immunol. 1993 May;13(3):204-11
references: 8320314
references: J Immunol. 1994 Mar 1;152(5):2488-95
references: 7510744
references: Pathobiology. 1995;63(2):76-82
references: 8554703
references: J Immunol Methods. 2012 Aug 31;382(1-2):32-9
references: 22580760
references: Autoimmun Rev. 2011 Jun;10(8):503-8
references: 21397735
references: Pharmacol Rep. 2009 Jan-Feb;61(1):22-32
references: 19307690
references: Clin Diagn Lab Immunol. 1999 Mar;6(2):156-60
references: 10066646
references: Cancer Res. 1993 Nov 1;53(21):5314-9
references: 8221667
references: Exp Hematol. 2003 Nov;31(11):1007-14
references: 14585362
references: Mod Rheumatol. 2008;18(6):570-7
references: 18568384