Online citations, reference lists, and bibliographies.
← Back to Search

Citrullinated Proteins: Sparks That May Ignite The Fire In Rheumatoid Arthritis

E. Vossenaar, W. V. van Venrooij
Published 2004 · Medicine

Cite This
Download PDF
Analyze on Scholarcy
Share
Antibodies directed to citrullinated proteins (e.g. anti-CCP [cyclic citrullinated peptide] antibodies) are highly specific for rheumatoid arthritis (RA). These antibodies are produced at the site of inflammation in RA, and therefore citrullinated antigens are also expected to be present in the inflamed synovium. We discuss literature showing that the presence of citrullinated proteins in the synovium is not specific for RA. The RA-specific antibodies are therefore most likely the result of an abnormal immune response that specifically occurs in RA patients. It was recently shown that presence of anti-CCP antibodies precedes the onset of clinical symptoms of RA by years. It thus appears that it may take years for initial events that cause the generation of anti-CCP antibodies to develop into full-blown disease.
This paper references
Is expres­ sion o f intracellu lar citrullinated proteins in synovial tissue specific fo r rheum atoid arthritis
TJ Smeets (2002)
10.1186/AR93
Rheumatoid arthritis associated autoantibodies in patients with synovitis of recent onset
R. Goldbach-Mansky (2000)
Antibodies against citrullinated peptide and IgA rheum atoid factor predict the developm ent o f rheum atoid arthritis
S Rantapää-Dahlqvist (2003)
10.1186/ar634
Subclass distribution of IgG autoantibodies to deiminated fibrinogen in rheumatoid arthritis
S. Chapuy-Regaud (2003)
itrullination, a possible functional link between susceptib ility genes and rheum atoid arthritis
ER Vossenaar (2004)
The major synovial targets o f the rheum atoid a rthritis-specific antifilaggrin autoantibodies are deim inated form s o f the alpha- and beta-chains o f fibrin
C Masson-Bessière (2001)
10.1002/ART.11223
Antibodies against cyclic citrullinated peptide and IgA rheumatoid factor predict the development of rheumatoid arthritis.
S. Rantapää-Dahlqvist (2003)
10.1016/S0140-6736(82)90735-8
ORIGIN AND SIGNIFICANCE OF RICE BODIES IN SYNOVIAL FLUID
DanielJ Mccarty (1982)
Apoptosis in rheum atoid arthritis
PP Tak (1999)
Anti-cyclic citru llinated peptide antibodies in advanced rheum atoid arthritis
GC Pinheiro (2003)
10.1002/1521-1878(200007)22:7<627::AID-BIES5>3.0.CO;2-K
Cell death: a trigger of autoimmunity?
R. Rodenburg (2000)
TW: In undifferentiated arthritis, autoantibodies to cyclic citrullinated peptides (CCP) predict progression to rheumatoid arthritis: a prospective cohort study
FA van Gaalen (2004)
10.1016/0378-5955(94)90125-2
Nitric oxide synthase is an active enzyme in the spiral ganglion cells of the rat cochlea
C. Zdanski (1994)
10.1006/BBRC.2001.6303
Deimination of arginine residues in nucleophosmin/B23 and histones in HL-60 granulocytes.
T. Hagiwara (2002)
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)
Expression and activity of citrullinating PAD enzymes in monocytes and macrophages
ER Vossenaar (2004)
Nitric oxide synthase is an active enzyme in the spiral ganglion cells o f the rat cochlea
CJ Zdanski (1994)
Extravascular fibrin form ation and d issolution in synovial tissue o f patients with osteoarthritis and rheum atoid arthritis
JB Weinberg (1991)
10.1186/ar578
Epidemiology and genetics of rheumatoid arthritis
A. Silman (2002)
10.1038/sj.cdd.4401042
Cleavage of plasma membrane calcium pumps by caspases: a link between apoptosis and necrosis
B. L. Schwab (2002)
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)
In the rheum atoid pannus, anti-filaggrin autoantibodies are pro­ duced by local plasma cells and constitu te a higher propor­ tion o f IgG than in synovial fluid and serum
C Masson-Bessière (2000)
10.1271/BBB1961.50.2899
Calcium-dependent Properties of Peptidylarginine Deiminase from Rabbit Skeletal Muscle(Biological Chemistry)
H. Takahara (1986)
A su pram icrom olar elevation o f intracellular free calcium ([Ca2+] i) is co n s is te n tly required to induce th e execution phase o f apoptosis. C ell Death Differ
B Tombal (2002)
C itru l ­ lination o f synovial proteins in m urine m odels o f rheumatoid arthritis
ER Vossenaar (2003)
10.1002/ART.1780340809
Extravascular fibrin formation and dissolution in synovial tissue of patients with osteoarthritis and rheumatoid arthritis.
J. Weinberg (1991)
In und iffe r­ entiated arthritis, autoantibodies to cyclic citru llinated pep­ tides (CCP) predict progression to rheum atoid arthritis: a prospective cohort study
FA van Gaalen (2004)
PAD, a growing fam ily o f citru llinating enzymes: genes, features and involvem ent in disease
ER Vossenaar (2003)
Secretion o f anti-citrulline-containing peptide antibody by B lym phocytes in rheum atoid arthritis
CC Reparon-Schuijt (2001)
Anticitrullinated p ro te in /peptide antibody and its role in the diagnosis and prognosis o f early rheum atoid arthritis
WJ van Venrooij (2002)
Rheumatoid arthritis associated autoan­ tibodies in patients with synovitis o f recent onset
R Goldbach-Mansky (2000)
The presence o f deim inated fibrin in the synovial m em brane is not specific fo r rheum atoid arthritis [ abstract ]
S Chapuy-Regaud (2004)
10.1074/jbc.M208795200
Nuclear Localization of Peptidylarginine Deiminase V and Histone Deimination in Granulocytes*
K. Nakashima (2002)
The presence o f deim inated fibrin in the synovial m em brane is not specific fo r rheum atoid arthritis
S Chapuy-Regaud (2004)
10.1016/S0198-8859(00)00185-3
HLA class II association with rheumatoid arthritis: facts and interpretations.
E. Zanelli (2000)
10.7326/0003-4819-139-3-200308050-00023
Anti-cyclic citrullinated peptide antibodies in advanced rheumatoid arthritis.
G. Pinheiro (2003)
10.1177/002215549804601110
Deimination of 70-kD Nuclear Protein During Epidermal Apoptotic Events In Vitro
M. Mizoguchi (1998)
10.1006/BBRC.1996.1240
Preferential deimination of keratin K1 and filaggrin during the terminal differentiation of human epidermis.
T. Senshu (1996)
10.1002/ART.20018
Specific autoantibodies precede the symptoms of rheumatoid arthritis: a study of serial measurements in blood donors.
M. Nielen (2004)
Selective deim ination of vim entin in calcium ionophore-induced apoptosis o f mouse peritoneal macrophages
H Asaga (1998)
Antibodies against citrullinated peptide and IgA rheumatoid factor predict the development of rheumatoid arthritis
S Rantapää-Dahlqvist (2003)
In undifferentiated arthritis , autoantibodies to cyclic citrullinated peptides ( CCP ) predict progression to rheumatoid arthritis : a prospective cohort study
FA vanGaalen (2004)
10.1186/ar660
Citrullination of synovial proteins in murine models of rheumatoid arthritis
E. Vossenaar (2003)
C itrullination , a possible functional link between susceptib ility genes and rheum atoid arthritis
ER Vossenaar (2004)
10.1186/ar1149
Rheumatoid arthritis specific anti-Sa antibodies target citrullinated vimentin
E. Vossenaar (2004)
10.1002/1529-0131(200110)44:10<2255::AID-ART388>3.0.CO;2
Specific presence of intracellular citrullinated proteins in rheumatoid arthritis synovium: relevance to antifilaggrin autoantibodies.
D. Baeten (2001)
utting edge: the conversion o f arginine to citru lline allows for a h igh-affin ity peptide interaction w ith the rheumatoid arthritis-associated HLA-DRB1*0401 MHC class II molecule
JA Hill (2003)
10.4049/jimmunol.171.2.538
Cutting Edge: The Conversion of Arginine to Citrulline Allows for a High-Affinity Peptide Interaction with the Rheumatoid Arthritis-Associated HLA-DRB1*0401 MHC Class II Molecule1
Jonathan A. Hill (2003)
10.1136/ARD.2003.012211
Expression and activity of citrullinating peptidylarginine deiminase enzymes in monocytes and macrophages.
E. Vossenaar (2004)
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)
10.1002/ART.10473
Is expression of intracellular citrullinated proteins in synovial tissue specific for rheumatoid arthritis? Comment on the article by Baeten et al.
T. Smeets (2002)
Subclass d istribution o f IgG autoantibodies to de im i­ nated fibrinogen in rheum atoid arthritis
S Chapuy-Regaud (2003)
Calcium -dependent properties o f peptidylarginine deim inase from rabbit skeletal muscle
H Takahara (1986)
A supram icrom olar elevation o f intracellular free calcium ([Ca2+] i) is consis­ tently required to induce the execution phase o f apoptosis
B Tombal (2002)
C utting edge : the conversion o f arginine to citru lline allows for a h igh - affin ity peptide interaction w ith the rheumatoid arthritis - associated HLA - DRB 1 * 0401 MHC class II molecule
JA Hill (2003)
10.1155/S0962935195000020
Apoptosis and inflammation
C. Haanen (1995)
Zeijlemaker WP: Human IgG Subclasses: Useful Diagnostic Markers for Immunocompetence, 2nd ed
AJ Meulenbroek (2000)
10.1136/ard.62.2.120
Anticitrullinated protein/peptide antibody assays in early rheumatoid arthritis for predicting five year radiographic damage
O. Meyer (2003)
Anticitrullinated protein/peptide antibody and its role in the diagnosis and prognosis of early rheumatoid arthritis.
W. V. van Venrooij (2002)
Subclass d istribution o f IgG autoantibodies to de im i ­ nated fibrinogen in rheum atoid arthritis [ abstract ]
S Chapuy-Regaud (2003)
Insights into rheum atoid arthritis derived from the Sa im m une system
HA Menard (2000)
Is expres ­ sion o f intracellu lar citrullinated proteins in synovial tissue specific fo r rheum atoid arthritis ? Com m ent on the article by Baeten et al . Arthritis Rheum
TJ Smeets (2002)
10.1006/BBRC.1998.8148
Selective deimination of vimentin in calcium ionophore-induced apoptosis of mouse peritoneal macrophages.
H. Asaga (1998)
10.1186/ar1027
Citrullination, a possible functional link between susceptibility genes and rheumatoid arthritis
E. Vossenaar (2004)
10.1002/1529-0131(200101)44:1<41::AID-ANR6>3.0.CO;2-0
Secretion of anti-citrulline-containing peptide antibody by B lymphocytes in rheumatoid arthritis.
C. C. Reparon-Schuijt (2001)
Anti-CCP antibodies, a specific marker for (early) rheumatoid arthritis
ER Vossenaar (2004)
10.1097/00002281-200305000-00015
Apoptosis in rheumatoid arthritis
A. Baier (2003)
10.1186/ar1062
The presence of deiminated fibrin in the synovial membrane is not specific for rheumatoid arthritis
S. Chapuy-Regaud (2004)
10.1186/ar122
Insights into rheumatoid arthritis derived from the Sa immune system
H. Ménard (2000)
The Sa system: a novel antigen-antibody system specific for rheumatoid arthritis.
N. Despres (1994)
Specific presence o f intracellular citrullinated proteins in rheum atoid arthritis synovium: relevance to an tifi­ laggrin autoantibodies
D Baeten (2001)
10.1016/J.CAIR.2003.11.001
Anti-CCP antibodies, a highly specific marker for (early) rheumatoid arthritis
E. Vossenaar (2004)
Anti-CCP antibodies, a specific marker for (early) rheum atoid arthritis
ER Vossenaar (2004)
Epidem iology and genetics o f rheum a­ toid arthritis
AJ Silman (2002)
LA: C itru l­ lination o f synovial proteins in m urine m odels o f rheumatoid arthritis
ER Vossenaar (2003)
Expression and activity o f c itru llinating PAD enzymes in m onocytes and macrophages
ER Vossenaar (2004)
Preferential deim ination o f keratin K1 and filaggrin during the term inal d if­ ferentiation o f human epiderm is
T Senshu (1996)
Diagnosing early-onset rheumatoid arthritis: the role of anti-CCP antibodies.
A. Vasishta (2002)
10.1126/SCIENCE.1071059
The Danger Model: A Renewed Sense of Self
P. Matzinger (2002)
10.1038/sj.cdd.4400999
A supramicromolar elevation of intracellular free calcium ([Ca2+]i) is consistently required to induce the execution phase of apoptosis
B. Tombal (2002)
Cleavage o f plasma mem brane calcium pum ps by caspases: a link between apoptosis and necrosis
BL Schwab (2002)
10.1002/ART.20044
Autoantibodies to cyclic citrullinated peptides predict progression to rheumatoid arthritis in patients with undifferentiated arthritis: a prospective cohort study.
F. V. van Gaalen (2004)



This paper is referenced by
10.1186/ar3848
T-cell autoreactivity to citrullinated autoantigenic peptides in rheumatoid arthritis patients carrying HLA-DRB1 shared epitope alleles
S. Law (2012)
10.1021/acs.molpharmaceut.8b00741
Sequential Prodrug Strategy To Target and Eliminate ACPA-Selective Autoreactive B Cells
Lianne P W M Lelieveldt (2018)
Review Article – Rheumatoid Arthritis, Diagnosis and Treatment
Maria Aziz (2016)
10.3390/nu11081821
The Microbial Metabolite Trimethylamine N-Oxide Links Vascular Dysfunctions and the Autoimmune Disease Rheumatoid Arthritis
M. Chan (2019)
10.1007/128_2011_302
ABPP methodology: introduction and overview.
Matthew B. Nodwell (2012)
10.1016/j.jmgm.2014.10.014
Theoretical study of the mechanism of protein arginine deiminase 4 (PAD4) inhibition by F-amidine.
Dongmei Li (2015)
10.1007/S11926-004-0008-1
Update on autoantibodies in rheumatoid arthritis
S. L. Bridges (2004)
10.4172/2155-9899.1000146
Citrullination: A target for disease intervention in multiple sclerosis and other inflammatory diseases?
R. G. Chirivi (2013)
Disorder Activity of Some Enzymes Plays an Important Role in Pathological Mechanism of Rheumatoid Arthritis Disease
M. B. Al (2015)
Ectopic lymphoid structures support Epstein-Barr virus persistence and autoreactive plasma cell infection in Rheumatoid Arthritis synovium and Sjogren’s Syndrome salivary glands
C. Croia (2013)
10.1007/s11926-012-0314-y
The Role of the Microbiome in Rheumatic Diseases
N. Yeoh (2013)
10.1007/s00281-006-0013-8
Biological therapies directed against cells in autoimmune disease
P. Hasler (2006)
Pristane-Induced Arthritis Stimulator of Autoimmunity in Rats with Autoantigen hnRNP-A 2 ( RA 33 ) Is a Major The Rheumatoid Arthritis-Associated and Günter
M. Hoffmann (2007)
10.1038/ncprheum0249
Mechanisms of Disease: genetic susceptibility and environmental triggers in the development of rheumatoid arthritis
L. Klareskog (2006)
10.1111/j.1747-0285.2006.00438.x
Synthesis of Overlapping Fibrin Citrullinated Peptides and their use for Diagnosing Rheumatoid Arthritis
M. L. Pérez (2006)
Investigation of possible immunological mechanisms in the pathogenesis of a murine model of rheumatoid arthritis
A. Hanyecz (2013)
10.1002/prca.201400013
Proteomics of citrullination in cardiovascular disease
Justyna Fert-Bober (2014)
10.1371/journal.pone.0174442
Periodontitis increases rheumatic factor serum levels and citrullinated proteins in gingival tissues and alter cytokine balance in arthritic rats
M. Corrêa (2017)
10.4172/2155-9899.S6-006
Anti-Citrullinated Protein Antibodies as Novel Therapeutic Drugs in Rheumatoid Arthritis
R. G. Chirivi (2013)
10.1016/j.rbre.2016.01.005
Independence of carbohydrate-deficient isoforms of transferrin and cyclic citrullinated peptides in rheumatoid arthritis.
Monika Gudowska (2017)
Citrullination : how subtle molecular changes affect loss of self-tolerance in rheumatoid arthritis
J. V. Beers (2006)
The influence of autoantibody status and characteristics on the course of rheumatoid arthritis
RHEUMATOID ARHTRITIS (2014)
10.1016/B978-0-12-095461-2.00038-2
Case Studies and Enrichment References
N. V. Bhagavan (2011)
10.1016/j.humimm.2017.05.005
PADI4 polymorphisms and the functional haplotype are associated with increased rheumatoid arthritis susceptibility: A replication study in a Southern Mexican population.
C. J. Baños-Hernández (2017)
10.1002/ART.22373
The HLA-DRB1 shared epitope alleles differ in the interaction with smoking and predisposition to antibodies to cyclic citrullinated peptide.
A. H. M. van der Helm-van Mil (2007)
10.1586/1744666X.3.2.187
Citrullinated collagens in the pathogenesis of rheumatoid arthritis
J. Risteli (2007)
10.1007/s10787-014-0205-0
Pharmacology of intra-articular triamcinolone
J. Scherer (2014)
10.1038/nrrheum.2011.204
The influence of ACPA status and characteristics on the course of RA
A. Willemze (2012)
10.4172/2155-9899.S6-008
Immunotherapy in Rheumatoid Arthritis: Prospects for the Restoration of Tolerance
Jenny L. McGovern (2013)
10.1590/S0100-879X2009000900010
Effect of the human leukocyte antigen HLA-DRB1 and anti-cyclic citrullinated peptide on the outcome of rheumatoid arthritis patients.
H. Farouk (2009)
10.1016/J.CCA.2006.12.002
Pathogenic implications for autoantibodies against C-reactive protein and other acute phase proteins.
C. Sjöwall (2007)
10.1007/s12016-007-8017-2
Share Epitope, Citrullinated Cyclic Peptide Antibodies and Smoking in Brazilian Rheumatoid Arthritis Patients
R. Oliveira (2008)
See more
Semantic Scholar Logo Some data provided by SemanticScholar