title: Anomalies of intra-synovial citrullination: is there any interest in the diagnosis of early rheumatoid arthritis?
abstract: Autoantibodies to citrullinated proteins (ACPA) are specifically associated with rheumatoid arthritis (RA) and seem to play an important role in its pathogenesis. The specific immunological conflict between ACPA and citrullinated fibrin plays a major role in the self-maintenance of synovial inflammation by forming fibrin deposits in the synovial tissue. These deposits, secondarily citrullinated by a local peptidylarginine deiminase (PADI) enzyme activity, seem to maintain the immunological conflict and the inflammation. Our objective in this work is to study the anomalies of citrullination in a group of patients with early RA, in comparison with a control group of patients suffering from undetermined inflammatory arthritis, osteoarthritis and spondyloarthropathy. For this purpose, we used an enzyme-linked immunosorbent assay (ELISA) to determine the levels of ACPA in serum and synovial fluid. By immunohistochemistry, subtype 4 of PADI was also sought in the synovial biopsies taken from all our patients. We found that the ACPA levels in serum and synovial fluid were significantly higher in patients with RA. The enzyme PADI4 was found only in the group with RA and was statistically correlated with ACPA mean levels in sera and synovial fluid. The expression of PADI4 seems to correlate with intra-synovial deposits of fibrin in RA. However, determination of synovial ACPA levels and detection of intra-synovial PADI4 deposits are of no additional benefit compared with assessment of ACPA levels in serum for the diagnosis of early RA.
authors.affiliation: Rheumatology Department, La Rabta Hospital, Tunis, Tunisia. mrabetdalila@yahoo.fr
authors.forename: Dalila
authors.initials: D
authors.lastname: Mrabet
authors.forename: Lilia
authors.initials: L
authors.lastname: Laadhar
authors.forename: Slim
authors.initials: S
authors.lastname: Haouet
authors.forename: Héla
authors.initials: H
authors.lastname: Sahli
authors.forename: Béchir
authors.initials: B
authors.lastname: Zouari
authors.forename: Sondès
authors.initials: S
authors.lastname: Makni
authors.forename: Slaheddine
authors.initials: S
authors.lastname: Sellami
mesh_terms: D000328:Adult; D001172:Arthritis, Rheumatoid / Q000175:diagnosis* / Q000378:metabolism; D001323:Autoantibodies / Q000097:blood; D002956:Citrulline / Q000378:metabolism*; D005260:Female; D006801:Humans; D006867:Hydrolases / Q000502:physiology; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000276:immunology; D000080002:Protein-Arginine Deiminase Type 4; D000076342:Protein-Arginine Deiminases; D013583:Synovial Membrane / Q000378:metabolism*
chemical_list: D001323:Autoantibodies; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide; D002956:Citrulline; D006867:Hydrolases; C000629235:PADI4 protein, human; D000080002:Protein-Arginine Deiminase Type 4; D000076342:Protein-Arginine Deiminases
references.citation: Ann Rheum Dis. 1999 Jan;58(1):42-8
references.pmid: 10343539
references.citation: Reumatismo. 2006 Apr-Jun;58(2):116-20
references.pmid: 16829989
references.citation: Rheumatol Int. 2007 Jul;27(9):827-33
references.pmid: 17265154
references.citation: Autoimmun Rev. 2005 Apr;4(4):201-6
references.pmid: 15893712
references.citation: Ann Rheum Dis. 2004 Dec;63(12):1587-93
references.pmid: 15547083
references.citation: Clin Exp Rheumatol. 2007 Jul-Aug;25(4):599-604
references.pmid: 17888217
references.citation: Ann Rheum Dis. 2006 Jul;65(7):845-51
references.pmid: 16606649
references.citation: Arthritis Rheum. 2006 Feb 15;55(1):53-6
references.pmid: 16463412
references.citation: Arthritis Res Ther. 2009;11(5):R146
references.pmid: 19796386
references.citation: Joint Bone Spine. 2009 Jul;76(4):343-9
references.pmid: 19524474
references.citation: J Clin Invest. 1995 Jun;95(6):2672-9
references.pmid: 7539459
references.citation: Joint Bone Spine. 2004 Nov;71(6):493-502
references.pmid: 15589429
references.citation: Rheumatol Int. 2010 Sep;30(11):1465-70
references.pmid: 19823836
references.citation: Best Pract Res Clin Rheumatol. 2009 Feb;23(1):37-48
references.pmid: 19233044
references.citation: Ann Rheum Dis. 1992 Jun;51(6):743-6
references.pmid: 1377463
references.citation: Ann Rheum Dis. 2008 Nov;67(11):1557-61
references.pmid: 18234714
references.citation: Scand J Rheumatol. 2005 May-Jun;34(3):212-5
references.pmid: 16134727
references.citation: Rheumatology (Oxford). 2005 Jan;44(1):40-50
references.pmid: 15466895