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Synovial Fluid Is A Site Of Citrullination Of Autoantigens In Inflammatory Arthritis.

Andrew J Kinloch, K. Lundberg, R. Wait, Natalia Wegner, N. H. Lim, A. J. W. Zendman, T. Saxne, V. Malmström, P. Venables
Published 2008 · Medicine

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OBJECTIVE To examine synovial fluid as a site for generating citrullinated antigens, including the candidate autoantigen citrullinated alpha-enolase, in rheumatoid arthritis (RA). METHODS Synovial fluid was obtained from 20 patients with RA, 20 patients with spondylarthritides (SpA), and 20 patients with osteoarthritis (OA). Samples were resolved using sodium dodecyl sulfate-polyacrylamide gel electrophoresis, followed by staining with Coomassie blue and immunoblotting for citrullinated proteins, alpha-enolase, and the deiminating enzymes peptidylarginine deiminase type 2 (PAD-2) and PAD-4. Proteins from an RA synovial fluid sample were separated by 2-dimensional electrophoresis, and each protein was identified by immunoblotting and mass spectrometry. Antibodies to citrullinated alpha-enolase peptide 1 (CEP-1) and cyclic citrullinated peptide 2 were measured by enzyme-linked immunosorbent assay. RESULTS Citrullinated polypeptides were detected in the synovial fluid from patients with RA and patients with SpA, but not in OA samples. Alpha-enolase was detected in all of the samples, with mean levels of 6.4 ng/microl in RA samples, 4.3 ng/microl in SpA samples, and <0.9 ng/microl in OA samples. Two-dimensional electrophoresis provided evidence that the alpha-enolase was citrullinated in RA synovial fluid. The citrullinating enzyme PAD-4 was detected in samples from all 3 disease groups. PAD-2 was detected in 18 of the RA samples, in 16 of the SpA samples, and in none of the OA samples. Antibodies to CEP-1 were found in 12 of the RA samples (60%), in none of the SpA samples, and in 1 OA sample. CONCLUSION These results highlight the importance of synovial fluid for the expression of citrullinated autoantigens in inflammatory arthritis. Whereas the expression of citrullinated proteins is a product of inflammation, the antibody response remains specific for RA.
This paper references
10.1002/ART.21220
Synovial intracellular citrullinated proteins colocalizing with peptidyl arginine deiminase as pathophysiologically relevant antigenic determinants of rheumatoid arthritis-specific humoral autoimmunity.
L. De Rycke (2005)
10.1186/ar1845
Identification of citrullinated α-enolase as a candidate autoantigen in rheumatoid arthritis
Andrew J Kinloch (2005)
10.1002/ART.22817
Mutation and citrullination modifies vimentin to a novel autoantigen for rheumatoid arthritis.
H. Bang (2007)
10.1038/ng1206
Functional haplotypes of PADI4, encoding citrullinating enzyme peptidylarginine deiminase 4, are associated with rheumatoid arthritis
A. Suzuki (2003)
10.1002/BIES.10357
PAD, a growing family of citrullinating enzymes: genes, features and involvement in disease
E. Vossenaar (2003)
10.4081/REUMATISMO.2006.116
[Usefulness of anti-cyclic citrullinate peptide antibody determination in synovial fluid analysis of patients with rheumatoid arthritis].
A. Spadaro (2006)
10.1002/prca.200600221
In pursuit of B‐cell synovial autoantigens in rheumatoid arthritis: Confirmation of citrullinated fibrinogen, detection of vimentin, and introducing carbonic anhydrase as a possible new synovial autoantigen
K. Tilleman (2007)
10.1136/ard.2005.044743
Citrullinated fibrinogen detected as a soluble citrullinated autoantigen in rheumatoid arthritis synovial fluids
Y. Takizawa (2006)
10.1002/ART.22276
Association of citrullinated proteins with synovial exosomes.
K. Skriner (2006)
10.4049/jimmunol.174.8.5057
Fibrin Deimination in Synovial Tissue Is Not Specific for Rheumatoid Arthritis but Commonly Occurs during Synovitides1
S. Chapuy-Regaud (2005)
10.1136/ARD.2003.012211
Expression and activity of citrullinating peptidylarginine deiminase enzymes in monocytes and macrophages.
E. Vossenaar (2004)
10.4049/jimmunol.166.6.4177
The Major Synovial Targets of the Rheumatoid Arthritis-Specific Antifilaggrin Autoantibodies Are Deiminated Forms of the α- and β-Chains of Fibrin1
C. Masson-Bessière (2001)
10.1586/1744666X.2.3.365
Pathogenic role of antibodies to citrullinated proteins in rheumatoid arthritis
Andrew J Kinloch (2006)
10.1136/ARD.2005.049403
Citrullination is an inflammation-dependent process.
D. Makrygiannakis (2006)
10.1186/ar2085
Identification of novel citrullinated autoantigens of synovium in rheumatoid arthritis using a proteomic approach
K. Matsuo (2006)
10.1046/j.1365-2249.2000.01171.x
In the rheumatoid pannus, anti‐filaggrin autoantibodies are produced by local plasma cells and constitute a higher proportion of IgG than in synovial fluid and serum
C. Masson-Bessière (2000)



This paper is referenced by
10.1021/cb200258q
Synthesis and screening of a haloacetamidine containing library to identify PAD4 selective inhibitors.
J. Jones (2012)
10.1080/14756366.2017.1368505
Reactive oxygen species inhibit catalytic activity of peptidylarginine deiminase
D. Damgaard (2017)
10.1016/j.ddtec.2012.06.002
Peptidylarginine deiminases: physiological function, interaction with chemokines and role in pathology.
E. Moelants (2012)
10.1002/bip.22127
The protein arginine deiminases: Structure, function, inhibition, and disease.
Kevin L Bicker (2013)
10.1016/j.bbrc.2016.10.154
Hypoxia-induced production of peptidylarginine deiminases and citrullinated proteins in malignant glioma cells.
T. Sase (2017)
10.1186/s13075-018-1533-z
Smoking is not linked to the development of anti-peptidylarginine deiminase 4 autoantibodies in rheumatoid arthritis
L. Cappelli (2018)
10.1186/ar3829
PAD4 is not essential for disease in the K/BxN murine autoantibody-mediated model of arthritis
Amanda S. Rohrbach (2012)
10.1186/ar3520
Detection of autoantibodies to citrullinated BiP in rheumatoid arthritis patients and pro-inflammatory role of citrullinated BiP in collagen-induced arthritis
H. Shoda (2011)
10.3389/fimmu.2018.02696
Autoantibodies to Peptidylarginine Deiminase 2 Are Associated With Less Severe Disease in Rheumatoid Arthritis
E. Darrah (2018)
Genetic and environmental determinants for disease risk in subsets of rheumatoid arthritis defi ned by the anticitrullinated protein / peptide antibody fi ne specifi city profi
K. Lundberg (2012)
10.1002/art.37720
The rheumatoid arthritis synovial fluid citrullinome reveals novel citrullinated epitopes in apolipoprotein E, myeloid nuclear differentiation antigen, and β-actin.
J. V. van Beers (2013)
10.3390/ijms21114015
Anti-Citrullinated Protein Antibodies in Patients with Rheumatoid Arthritis: Biological Effects and Mechanisms of Immunopathogenesis
Chao-Yi Wu (2020)
10.1371/journal.pone.0203214
Relative efficiencies of peptidylarginine deiminase 2 and 4 in generating target sites for anti-citrullinated protein antibodies in fibrinogen, alpha-enolase and histone H3
D. Damgaard (2018)
10.1016/j.jaut.2017.01.006
Peptidylarginine deiminase 2 is required for tumor necrosis factor alpha-induced citrullination and arthritis, but not neutrophil extracellular trap formation.
M. Bawadekar (2017)
Functional and transcriptional characterisation of synovial fibroblasts in early inflammatory arthritis and established rheumatoid arthritis
J. Pérez (2015)
10.1002/9781119250906.CH7
The Deimination of Arginine to Citrulline
Andrew J Creese (2016)
10.1016/j.jaut.2012.03.004
Neuronal PAD4 expression and protein citrullination: possible role in production of autoantibodies associated with neurodegenerative disease.
Nimish K. Acharya (2012)
TITLE : THE ROLE OF RHEUMATOID FACTOR IN THE DIAGNOSIS OF RHEUMATOID ARTHRITIS
F. Khan (2012)
10.1016/j.biochi.2012.09.029
Peptidylarginine deiminase expression and activity in PAD2 knock-out and PAD4-low mice.
Joyce J.B.C. van Beers (2013)
10.1155/2019/7592851
An Overview of the Intrinsic Role of Citrullination in Autoimmune Disorders
Mohammed I. Alghamdi (2019)
10.1002/art.30639
Immunization with Porphyromonas gingivalis enolase induces autoimmunity to mammalian α-enolase and arthritis in DR4-IE-transgenic mice.
Andrew J Kinloch (2011)
Outcomes of Periodontal Treatment in Patients with Rheumatoid Arthritis (OPERA) : quantitative and qualitative results of a pilot randomized controlled trial
S. Serban (2017)
10.1111/j.0105-2896.2009.00856.x
The role of antibodies in inflammatory arthritis
Ann Duskin (2010)
10.1186/ar3740
Inhibiting citrullination in rheumatoid arthritis: taking fuel from the fire
B. Fisher (2012)
10.4172/IJM.1000122
Link between Dimethyl arginine Derivats and Acpa Antibodies in Patients with Rheumatoid Arthritis
T. SpasovskiDandSotirova (2014)
Pathogenetic factors of importance for the development and progression of rheumatoid arthritis
Heidi Kokkonen (2012)
Design Synthesis and Evaluation of Novel Anti rheumatic Agents
Vadiraj Kurdekar (2014)
10.1186/ar4093
Polymorphisms in peptidylarginine deiminase associate with rheumatoid arthritis in diverse Asian populations: evidence from MyEIRA study and meta-analysis
C. L. Too (2012)
10.4172/2155-9899.S6-006
Anti-Citrullinated Protein Antibodies as Novel Therapeutic Drugs in Rheumatoid Arthritis
R. G. Chirivi (2013)
10.3390/antib6020006
Collagen Autoantibodies and Their Relationship to CCP Antibodies and Rheumatoid Factor in the Progression of Early Rheumatoid Arthritis
S. Whittingham (2017)
10.1111/cbdd.12526
PAD2 Activity Monitored via a Fluorescent Substrate Analog
Mary J Sabulski (2015)
10.1371/journal.pone.0150784
Characterization and Localization of Citrullinated Proteoglycan Aggrecan in Human Articular Cartilage
T. Glant (2016)
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