title: IgG subclass distribution of the rheumatoid arthritis-specific autoantibodies to citrullinated fibrin.
abstract: In the rheumatoid synovium, deiminated ('citrullinated') forms of fibrin are the major targets of IgG autoantibodies to citrullinated proteins (ACPA), the most specific serological markers of rheumatoid arthritis (RA). To further the characterization of ACPA, we determined their subclass distribution. From a previously validated highly sensitive and specific enzyme-linked immunosorbent assay (ELISA) onto in vitro deiminated human fibrinogen - antihuman fibrin(ogen) autoantibodies (AhFibA)-ELISA - we derived and calibrated four ELISAs, using monoclonal antibodies to each of the four IgG subclasses, to determine the proportions of AhFibA subclasses in the sera. A series of 186 serum samples from RA patients was analysed. All AhFibA-positive sera contained IgG1-AhFibA, which reached the highest titres and accounted for more than 80% of AhFibA in three-quarters of the sera. One or two other subclasses were associated with IgG1 in 39% of the sera, IgG4-AhFibA being observed much more frequently and at higher titres than IgG3- or IgG2-AhFibA. IgG1 alone or IgG(1 + 4)-AhFibA were the AhFibA subclass profiles found in more than 80% of patients. AhFibA are mainly IgG1 and, to a lesser extent, IgG4. Such IgG subclass profiles may influence the effector phases of the immunological conflict between ACPA and deiminated fibrin that takes place specifically in the rheumatoid synovium and therefore may play a critical role in the self-maintenance of rheumatoid inflammation.
authors.affiliation: Laboratory of 'Epidermis Differentiation and Rheumatoid Autoimmunity', UMR 5165 CNRS-Toulouse III University, Toulouse, France.
authors.forename: S
authors.initials: S
authors.lastname: Chapuy-Regaud
authors.forename: L
authors.initials: L
authors.lastname: Nogueira
authors.forename: C
authors.initials: C
authors.lastname: Clavel
authors.forename: M
authors.initials: M
authors.lastname: Sebbag
authors.forename: C
authors.initials: C
authors.lastname: Vincent
authors.forename: G
authors.initials: G
authors.lastname: Serre
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D002956:Citrulline / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D005337:Fibrin / Q000276:immunology*; D005340:Fibrinogen / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D008297:Male; D008875:Middle Aged
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D007074:Immunoglobulin G; D002956:Citrulline; D005337:Fibrin; D005340:Fibrinogen
references.citation: Clin Exp Immunol. 2000 May;120(2):369-74
references.pmid: 10792390
references.citation: Arthritis Rheum. 2000 Apr;43(4):740-52
references.pmid: 10765918
references.citation: Br J Dermatol. 2000 Aug;143(2):337-42
references.pmid: 10951142
references.citation: Ann Rheum Dis. 2001 Jan;60(1):32-5
references.pmid: 11114279
references.citation: J Immunol. 2001 Mar 15;166(6):4177-84
references.pmid: 11238669
references.citation: Br J Dermatol. 2001 Apr;144(4):760-8
references.pmid: 11298534
references.citation: Arthritis Rheum. 2001 Apr;44(4):739-50
references.pmid: 11315912
references.citation: Ann Rheum Dis. 2001 Sep;60(9):882-7
references.pmid: 11502616
references.citation: Trends Immunol. 2001 Sep;22(9):510-6
references.pmid: 11525942
references.citation: Scand J Rheumatol. 2001;30(4):221-4
references.pmid: 11578017
references.citation: J Immunol. 2002 Jan 15;168(2):545-53
references.pmid: 11777945
references.citation: Immunity. 2002 Feb;16(2):157-68
references.pmid: 11869678
references.citation: Arthritis Rheum. 2002 Apr;46(4):934-45
references.pmid: 11953970
references.citation: Arthritis Rheum. 2002 May;46(5):1185-95
references.pmid: 12115222
references.citation: Clin Exp Immunol. 2002 Sep;129(3):549-55
references.pmid: 12197898
references.citation: Arthritis Rheum. 2002 Aug;46(8):2051-8
references.pmid: 12209508
references.citation: Blood. 1997 Aug 1;90(3):1109-14
references.pmid: 9242542
references.citation: J Clin Invest. 1998 Jan 1;101(1):273-81
references.pmid: 9421490
references.citation: Arthritis Rheum. 1998 Jan;41(1):48-57
references.pmid: 9433869
references.citation: J Exp Med. 1998 Feb 16;187(4):641-8
references.pmid: 9463414
references.citation: Infect Immun. 1998 Mar;66(3):1057-62
references.pmid: 9488395
references.citation: Int Arch Allergy Immunol. 1998 Apr;115(4):294-302
references.pmid: 9566352
references.citation: J Rheumatol. 1998 May;25(5):838-46
references.pmid: 9598877
references.citation: J Rheumatol. 1998 Aug;25(8):1466-71
references.pmid: 9712085
references.citation: J Immunol. 1999 Jan 1;162(1):585-94
references.pmid: 9886436
references.citation: Immunity. 1999 Apr;10(4):451-61
references.pmid: 10229188
references.citation: Immunology. 1999 Mar;96(3):358-64
references.pmid: 10233716
references.citation: Rheumatology (Oxford). 1999 Mar;38(3):214-20
references.pmid: 10325659
references.citation: Ann Rheum Dis. 1964 Jul;23:302-5
references.pmid: 14178016
references.citation: Ann Rheum Dis. 2004 Dec;63(12):1587-93
references.pmid: 15547083
references.citation: J Invest Dermatol. 2003 Jan;120(1):104-8
references.pmid: 12535205
references.citation: Rheumatology (Oxford). 2003 Apr;42(4):528-33
references.pmid: 12649399
references.citation: Ann Rheum Dis. 2003 May;62(5):427-30
references.pmid: 12695154
references.citation: J Rheumatol. 2003 May;30(5):926-33
references.pmid: 12734884
references.citation: Arthritis Rheum. 2004 Feb;50(2):380-6
references.pmid: 14872479
references.citation: Arthritis Rheum. 2004 Mar;50(3):709-15
references.pmid: 15022309
references.citation: Br Med J. 1979 Jul 14;2(6182):97-9
references.pmid: 111762
references.citation: Arthritis Rheum. 1984 Aug;27(8):845-51
references.pmid: 6466393
references.citation: Immunol Lett. 1985;10(3-4):223-52
references.pmid: 3899923
references.citation: J Immunol. 1987 Sep 1;139(5):1466-71
references.pmid: 3624864
references.citation: Arthritis Rheum. 1988 Mar;31(3):315-24
references.pmid: 3358796
references.citation: Clin Exp Immunol. 1990 Jul;81(1):83-9
references.pmid: 1696185
references.citation: Arthritis Rheum. 1992 Aug;35(8):914-7
references.pmid: 1379430
references.citation: Rheumatol Int. 1994;14(1):13-9
references.pmid: 7939135
references.citation: Ann Rheum Dis. 1994 Nov;53(11):735-42
references.pmid: 7529986
references.citation: Proc Natl Acad Sci U S A. 1995 May 23;92(11):5239-43
references.pmid: 7761479
references.citation: J Clin Invest. 1995 Jun;95(6):2672-9
references.pmid: 7539459
references.citation: Curr Opin Immunol. 1996 Apr;8(2):199-205
references.pmid: 8725943
references.citation: Ann Rheum Dis. 1997 Feb;56(2):123-5
references.pmid: 9068286
references.citation: Arthritis Rheum. 2000 Jan;43(1):155-63
references.pmid: 10643712
references.citation: Clin Exp Immunol. 2000 Mar;119(3):544-52
references.pmid: 10691929
references.citation: Mol Immunol. 1999 Sep-Oct;36(13-14):905-14
references.pmid: 10698345
references.citation: Ann Rheum Dis. 2000 Apr;59(4):263-8
references.pmid: 10733472
references.citation: Arthritis Rheum. 2000 Aug;43(8):1831-5
references.pmid: 10943873