Skip to main content
Top
Published in: Clinical Reviews in Allergy & Immunology 1/2008

01-02-2008

Does the Presence of Anti-CCP Autoantibodies and Their Serum Levels Influence the Severity and Activity in Rheumatoid Arthritis Patients?

Authors: Nikolaos G. Papadopoulos, Georgios Z. Tsiaousis, Aikaterini Pavlitou-Tsiontsi, Anastasia Giannakou, Vassiliki K. Galanopoulou

Published in: Clinical Reviews in Allergy & Immunology | Issue 1/2008

Login to get access

Abstract

This study aims to investigate the association of the presence and of the titer of autoantibodies against cyclic citrullinated peptides (aCCP), with clinical manifestations and disease activity in a cohort of patients with rheumatoid arthritis (RA). From January 2000 through December 2005, 135 patients were diagnosed with RA at the Rheumatology Unit of our hospital. Demographic, clinical, laboratory, and therapeutic parameters were evaluated in all patients at study entry and at every follow-up visit. Positivity in aCCP and also their levels were determined for all patients. At the end of the study, we reevaluated the above parameters, dividing patients into aCCP positive and aCCP negative. From 135 patients, 53.3% were aCCP positive. The majority of aCCP-positive patients were males (p < 0.001), positive to rheumatoid factor (p < 0.001) and current smokers (p < 0.05). At diagnosis, aCCP-positive patients presented with higher tender joint counts (p < 0.001) and swollen joint counts (p < 0.001), and exhibited more active disease, expressed by higher disease activity scores for 28 joints (DAS-28) (p < 0.001). At the end of the study, aCCP-positive patients also displayed more active disease, with higher DAS-28 (p < 0.001), and more severe disease, as this was indicated by the higher radiological Larsen score (p < 0.001). The serum levels of aCCP were not found to be associated with disease activity and severity. In early RA, the presence of aCCP is associated with increased disease activity and severity. This was found to be independent of circulating levels of aCCP.
Literature
1.
go back to reference Hochberg MC, Spector TD (1990) Epidemiology of Rheumatoid Arthritis. Update. Epidemiol Rev 12:247–252PubMed Hochberg MC, Spector TD (1990) Epidemiology of Rheumatoid Arthritis. Update. Epidemiol Rev 12:247–252PubMed
2.
go back to reference Hochberg MC (1994) Predicting the prognosis of patients with rheumatoid arthritis. Is there a crystal ball? J Rheumatol 20:1265–1267 Hochberg MC (1994) Predicting the prognosis of patients with rheumatoid arthritis. Is there a crystal ball? J Rheumatol 20:1265–1267
3.
go back to reference Turesson C, O’Fallon MW, Crowson CS, Gabriel SE, Matteson EL (2002) Occurrence of extra-articular disease manifestation is associated with excess mortality in a community-based cohort of patients with rheumatoid arthritis. J Rheumatol 29:62–67PubMed Turesson C, O’Fallon MW, Crowson CS, Gabriel SE, Matteson EL (2002) Occurrence of extra-articular disease manifestation is associated with excess mortality in a community-based cohort of patients with rheumatoid arthritis. J Rheumatol 29:62–67PubMed
4.
go back to reference Arnett FC, Edworthy SM, Bloch DA et al (1988) The American Rheumatism Association 1987 criteria for the classification of rheumatoid arthritis. Arthritis Rheum 31:315–324PubMedCrossRef Arnett FC, Edworthy SM, Bloch DA et al (1988) The American Rheumatism Association 1987 criteria for the classification of rheumatoid arthritis. Arthritis Rheum 31:315–324PubMedCrossRef
5.
go back to reference Quinn MA, Green MS, Emery P (1997) Evaluation and management of early inflammatory arthritis severity. Ann Rheum Dis 56:463–469CrossRef Quinn MA, Green MS, Emery P (1997) Evaluation and management of early inflammatory arthritis severity. Ann Rheum Dis 56:463–469CrossRef
6.
go back to reference Avouac J, Gossec L, Dougados M (2006) Diagnostic and predictive value of anticyclic citrullinated protein antibodies in rheumatoid arthritis: a systematic literature review. Ann Rheum Dis 65:845–851PubMedCrossRef Avouac J, Gossec L, Dougados M (2006) Diagnostic and predictive value of anticyclic citrullinated protein antibodies in rheumatoid arthritis: a systematic literature review. Ann Rheum Dis 65:845–851PubMedCrossRef
7.
go back to reference Zendman AJW, van Venrooij WJ, Pruijn GJM (2006) Use and significance of anti-CCP autoantibodies in rheumatoid arhritis. Rheumatology 45:20–25PubMedCrossRef Zendman AJW, van Venrooij WJ, Pruijn GJM (2006) Use and significance of anti-CCP autoantibodies in rheumatoid arhritis. Rheumatology 45:20–25PubMedCrossRef
8.
go back to reference Ates A, Karaaslan Y, Aksaray S (2006) Predictive value of autoantibodies to cyclic citrullinated peptide in patients with early arthritis. Clin Rheumatol 25:743–745CrossRef Ates A, Karaaslan Y, Aksaray S (2006) Predictive value of autoantibodies to cyclic citrullinated peptide in patients with early arthritis. Clin Rheumatol 25:743–745CrossRef
9.
go back to reference Larsen A, Dale K, Eek M (1977) Radiographic evaluation of rheumatoid arthritis and related conditions by standard reference films. Acta Radiol Diagn (Stockh) 18:481–491 Larsen A, Dale K, Eek M (1977) Radiographic evaluation of rheumatoid arthritis and related conditions by standard reference films. Acta Radiol Diagn (Stockh) 18:481–491
10.
go back to reference Davis MG, Dawes PT, Fowler PD et al (1990) Comparison and evaluation of a disease activity index for use in patients with rheumatoid arthritis. Br J Rheumatol 29:111–115PubMedCrossRef Davis MG, Dawes PT, Fowler PD et al (1990) Comparison and evaluation of a disease activity index for use in patients with rheumatoid arthritis. Br J Rheumatol 29:111–115PubMedCrossRef
11.
go back to reference Von Schaardenbourg D, Hazes IMW, de Boer A (1993) Outcome of rheumatoid arthritis relation to age and rheumatoid factors at diagnosis. J Rheumatol 20:45–52 Von Schaardenbourg D, Hazes IMW, de Boer A (1993) Outcome of rheumatoid arthritis relation to age and rheumatoid factors at diagnosis. J Rheumatol 20:45–52
12.
go back to reference Houssien DA, Jonsson T, Davies E, Scott D (1998) Rheumatoid factors isotypes, disease activity and the outcome of rheumatoid arthritis. Scand J Rheumatol 27:46–53PubMedCrossRef Houssien DA, Jonsson T, Davies E, Scott D (1998) Rheumatoid factors isotypes, disease activity and the outcome of rheumatoid arthritis. Scand J Rheumatol 27:46–53PubMedCrossRef
13.
go back to reference Mattey DL, Dawes PT, Clarke S et al (2002) Relationship among the HLA-DRB1 shared epitope, smoking, and rheumatoid factor production in rheumatoid arthritis. Arthritis Rheum 47:403–407PubMedCrossRef Mattey DL, Dawes PT, Clarke S et al (2002) Relationship among the HLA-DRB1 shared epitope, smoking, and rheumatoid factor production in rheumatoid arthritis. Arthritis Rheum 47:403–407PubMedCrossRef
14.
go back to reference De Rycke L, Peene I, Hoffman IG et al (2004) Rheumatoid factor and anticitrullinated protein antibodies in rheumatoid arthritis: diagnostic value, associations with radiological progression rate, and extra-articular manifestations. Ann Rheum Dis 63:1587–1593PubMedCrossRef De Rycke L, Peene I, Hoffman IG et al (2004) Rheumatoid factor and anticitrullinated protein antibodies in rheumatoid arthritis: diagnostic value, associations with radiological progression rate, and extra-articular manifestations. Ann Rheum Dis 63:1587–1593PubMedCrossRef
15.
go back to reference Herold M, Boeser V, Russe E, Klotz W (2005) Anti-CCP: history and its usefulness. Clin Dev Immunol 12:131–135PubMedCrossRef Herold M, Boeser V, Russe E, Klotz W (2005) Anti-CCP: history and its usefulness. Clin Dev Immunol 12:131–135PubMedCrossRef
16.
go back to reference Lee W, Weisman MH (2006) The predictive power of anti-cyclic citrullinated peptide antibodies: window into understanding gene/environment/immunity intractions. J Rheumatol 33:1216–1217PubMed Lee W, Weisman MH (2006) The predictive power of anti-cyclic citrullinated peptide antibodies: window into understanding gene/environment/immunity intractions. J Rheumatol 33:1216–1217PubMed
17.
go back to reference Russell AS, Devani A, Maksymowych WP (2006) The role of anti-cyclic citrullinated peptide antibodies in predicting progression of palindromic rheumatism to rheumatoid arthritis. J Rheumatol 33:1240–1242PubMed Russell AS, Devani A, Maksymowych WP (2006) The role of anti-cyclic citrullinated peptide antibodies in predicting progression of palindromic rheumatism to rheumatoid arthritis. J Rheumatol 33:1240–1242PubMed
18.
go back to reference Kaltenhauser S, Pierer M, Arnold S, Kamprad M, Baerwald C, Hantzschel, H, Wagner U (2007) Antibodies against cyclic citrullinated peptide are associated with the DRB1 shared epitope and predict joint erosion in rheumatoid arthritis. Rheumatology (Oxford) 46:100–104CrossRef Kaltenhauser S, Pierer M, Arnold S, Kamprad M, Baerwald C, Hantzschel, H, Wagner U (2007) Antibodies against cyclic citrullinated peptide are associated with the DRB1 shared epitope and predict joint erosion in rheumatoid arthritis. Rheumatology (Oxford) 46:100–104CrossRef
19.
go back to reference Nell VP, Machold KP, Stamm TA et al (2005) Autoantibody profiling as early diagnostic and prognostic tool for rheumatoid arthritis. Ann Rheum Dis 64:1731–1736PubMedCrossRef Nell VP, Machold KP, Stamm TA et al (2005) Autoantibody profiling as early diagnostic and prognostic tool for rheumatoid arthritis. Ann Rheum Dis 64:1731–1736PubMedCrossRef
20.
go back to reference Skogh T (2005) Does positive anti-CCP test identify a distinct arthritis entity? Arthritis Res Ther 7:R230–232CrossRef Skogh T (2005) Does positive anti-CCP test identify a distinct arthritis entity? Arthritis Res Ther 7:R230–232CrossRef
21.
go back to reference van der Helm-van Mil AHM, Verpoort KN, Breedveld FC, Toes RE, Huizinga TW (2005) Antibodies to citrullinated proteins and differences in clinical progression of rheumatoid arthritis. Arthritis Res Ther 7:R949–R958PubMedCrossRef van der Helm-van Mil AHM, Verpoort KN, Breedveld FC, Toes RE, Huizinga TW (2005) Antibodies to citrullinated proteins and differences in clinical progression of rheumatoid arthritis. Arthritis Res Ther 7:R949–R958PubMedCrossRef
22.
go back to reference Samanci N, Ozdem S, Akbas H, Mutlu D, Gultekin M, Arman M, Donmez, L (2005) Diagnostic value and clinical significance of anti-CCP in patients with advanced rheumatoid arthritis. J Natl Med Assoc 97:1120–1126PubMed Samanci N, Ozdem S, Akbas H, Mutlu D, Gultekin M, Arman M, Donmez, L (2005) Diagnostic value and clinical significance of anti-CCP in patients with advanced rheumatoid arthritis. J Natl Med Assoc 97:1120–1126PubMed
23.
go back to reference Quinn MA, Gough AK, Green MJ, Devlin J, Greenstein A, Fraser A, Emery P (2006) Anti-CCP antibodies measured at disease onset help identify seronegative rheumatoid arthritis and predict radiological and functional outcome. Rheumatology (Oxford) 45:478–480CrossRef Quinn MA, Gough AK, Green MJ, Devlin J, Greenstein A, Fraser A, Emery P (2006) Anti-CCP antibodies measured at disease onset help identify seronegative rheumatoid arthritis and predict radiological and functional outcome. Rheumatology (Oxford) 45:478–480CrossRef
24.
go back to reference Mewar D, Coote A, Moore DJ, Marinou L, Dickson MC, Montgomery DS, Binks MH, Wilson AG (2006) Independent associations of anti-cyclic citrullinated peptide antibodies and rheumatoid factor with radiographic severity of rheumatoid arthritis. Arthritis Res Ther 8:R128PubMedCrossRef Mewar D, Coote A, Moore DJ, Marinou L, Dickson MC, Montgomery DS, Binks MH, Wilson AG (2006) Independent associations of anti-cyclic citrullinated peptide antibodies and rheumatoid factor with radiographic severity of rheumatoid arthritis. Arthritis Res Ther 8:R128PubMedCrossRef
25.
go back to reference Korkmaz C, Us T, Kasifoglou T, Akgun Y (2006) Anti-cyclic citrullinated peptide (CCP) antibodies in patients with long-standing rheumatoid arthritis and their relationship with extra-articular manifestations. Clin Biochem 39:961–965PubMedCrossRef Korkmaz C, Us T, Kasifoglou T, Akgun Y (2006) Anti-cyclic citrullinated peptide (CCP) antibodies in patients with long-standing rheumatoid arthritis and their relationship with extra-articular manifestations. Clin Biochem 39:961–965PubMedCrossRef
26.
go back to reference Agrawal S, Misra R, Aggarwal A (2007) Autoantibodies in rheumatoid arthritis: associaton with severity of disease in established RA. Clin Rheumatol 26:201–204PubMedCrossRef Agrawal S, Misra R, Aggarwal A (2007) Autoantibodies in rheumatoid arthritis: associaton with severity of disease in established RA. Clin Rheumatol 26:201–204PubMedCrossRef
27.
go back to reference Turesson C, Jacobsson LT, Sturfelt G, Matteson EL, Mathsson L, Ronnelid, J (2007) Rheumatoid factor and antibodies to cyclic citrullinated peptides are associated with severe extra-articular manifestations in rheumatoid arthritis. Ann Rheum Dis 66:59–64PubMedCrossRef Turesson C, Jacobsson LT, Sturfelt G, Matteson EL, Mathsson L, Ronnelid, J (2007) Rheumatoid factor and antibodies to cyclic citrullinated peptides are associated with severe extra-articular manifestations in rheumatoid arthritis. Ann Rheum Dis 66:59–64PubMedCrossRef
28.
go back to reference Aotsuka S, Okawa-Takatsuji M, Nagatani K, Nagashio C, Kano T, Nakajima K, Ito K, Mimori A (2005) A retrospective study of the fluctuation in serum levels of anti-cyclic citrullinated peptide antibody in patients with rheumatoid arthritis. Clin Exp Rheumatol 23:475–481PubMed Aotsuka S, Okawa-Takatsuji M, Nagatani K, Nagashio C, Kano T, Nakajima K, Ito K, Mimori A (2005) A retrospective study of the fluctuation in serum levels of anti-cyclic citrullinated peptide antibody in patients with rheumatoid arthritis. Clin Exp Rheumatol 23:475–481PubMed
29.
go back to reference Del Val del Amo N, Ibanez Bosch R, Fito Manteca C, Loza Cortina E (2006) Anticyclic citrullinated peptide antibody in rheumatoid arthritis: relation with disease aggressiveness. Clin Exp Rheumatol 24:281–286PubMed Del Val del Amo N, Ibanez Bosch R, Fito Manteca C, Loza Cortina E (2006) Anticyclic citrullinated peptide antibody in rheumatoid arthritis: relation with disease aggressiveness. Clin Exp Rheumatol 24:281–286PubMed
30.
go back to reference Berglin E, Johansson T, Sundin U, Jidell E, Wadell G, Hallmans G, Rantapaa-Dahlqvist S (2006) Radiological outcome in rheumatoid arthritis is predicted by presence of antibodies against cyclic citrullinated peptide before and at disease onset, and by IgA-RF at disease onset and IgA rheumatoid factors with serological parameters of disease activity in rheumatoid arthritis. Ann Rheum Dis 65:453–458PubMedCrossRef Berglin E, Johansson T, Sundin U, Jidell E, Wadell G, Hallmans G, Rantapaa-Dahlqvist S (2006) Radiological outcome in rheumatoid arthritis is predicted by presence of antibodies against cyclic citrullinated peptide before and at disease onset, and by IgA-RF at disease onset and IgA rheumatoid factors with serological parameters of disease activity in rheumatoid arthritis. Ann Rheum Dis 65:453–458PubMedCrossRef
31.
go back to reference Greiner A, Plischke H, Kellner H, Gruber R (2005) Association of anti-cyclic citrullinated peptide antibodies, anti-citrulline antibodies, and IgM and IgA rheumatoid factors with serological parameters of disease activity in rheumatoid arthritis. Ann N Y Acad Sci 1050:295–303PubMedCrossRef Greiner A, Plischke H, Kellner H, Gruber R (2005) Association of anti-cyclic citrullinated peptide antibodies, anti-citrulline antibodies, and IgM and IgA rheumatoid factors with serological parameters of disease activity in rheumatoid arthritis. Ann N Y Acad Sci 1050:295–303PubMedCrossRef
32.
go back to reference Hitchon CA, Alex P, Erdile LB, Frank MB, Dozmorov I, Tang Y, Wong K, Centola M, El-Gabalawy HS (2004) A distinct multicytokine profile is associated with anti-cyclical citrullinated peptide in patients with early untreated inflammatory arthritis. J Rheumatol 31:2336–2346PubMed Hitchon CA, Alex P, Erdile LB, Frank MB, Dozmorov I, Tang Y, Wong K, Centola M, El-Gabalawy HS (2004) A distinct multicytokine profile is associated with anti-cyclical citrullinated peptide in patients with early untreated inflammatory arthritis. J Rheumatol 31:2336–2346PubMed
33.
go back to reference Albano S, Santana-Sahagun E, Weisman MH (2001) Cigarette smoking and rheumatoid arthritis. Semin Arthritis Rheum 31:146–159PubMedCrossRef Albano S, Santana-Sahagun E, Weisman MH (2001) Cigarette smoking and rheumatoid arthritis. Semin Arthritis Rheum 31:146–159PubMedCrossRef
34.
go back to reference Papadopoulos NG, Alamanos Y, Voulgari PV, Epagelis EK, Tsifetaki N, Drosos AA (2005) Does cigarette smoking influence disease expression, activity and severity in early rheumatoid arthritis patients? Clin Exp Rheumatol 23:861–866PubMed Papadopoulos NG, Alamanos Y, Voulgari PV, Epagelis EK, Tsifetaki N, Drosos AA (2005) Does cigarette smoking influence disease expression, activity and severity in early rheumatoid arthritis patients? Clin Exp Rheumatol 23:861–866PubMed
35.
go back to reference Linn-Rasker SP, van der Helm-van Mil AH, van Gaalen FA, Kloppenburg M, de Vries RR, le Ccessie S, Breedveld FC, Toes RE, Huizinga TW (2006) Smoking is a risk factor for anti-CCP antibodies only in rheumatoid arthritis patients who carry HLA-DRB1 shared epitope alleles. Ann Rheum Dis 65:366–371PubMedCrossRef Linn-Rasker SP, van der Helm-van Mil AH, van Gaalen FA, Kloppenburg M, de Vries RR, le Ccessie S, Breedveld FC, Toes RE, Huizinga TW (2006) Smoking is a risk factor for anti-CCP antibodies only in rheumatoid arthritis patients who carry HLA-DRB1 shared epitope alleles. Ann Rheum Dis 65:366–371PubMedCrossRef
Metadata
Title
Does the Presence of Anti-CCP Autoantibodies and Their Serum Levels Influence the Severity and Activity in Rheumatoid Arthritis Patients?
Authors
Nikolaos G. Papadopoulos
Georgios Z. Tsiaousis
Aikaterini Pavlitou-Tsiontsi
Anastasia Giannakou
Vassiliki K. Galanopoulou
Publication date
01-02-2008
Publisher
Humana Press Inc
Published in
Clinical Reviews in Allergy & Immunology / Issue 1/2008
Print ISSN: 1080-0549
Electronic ISSN: 1559-0267
DOI
https://doi.org/10.1007/s12016-007-8018-1

Other articles of this Issue 1/2008

Clinical Reviews in Allergy & Immunology 1/2008 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.