Abstract
Anti-cyclic citrullinated peptide (anti-CCP) antibody is highly specific for diagnosing rheumatoid arthritis (RA). Cigarette smoking is a lifestyle and environmental factor associated with anti-CCP production and is strongly associated with chronic obstructive pulmonary disease (COPD). This study assessed levels of anti-CCP antibodies and rheumatoid factor (RF) among patients with RA and COPD. The study sample comprised 63 patients with RA and 70 patients with COPD, all of whom underwent assessment of anti-CCP antibody and RF levels. Testing revealed that 54.2 % of RA patients and 0 % of COPD patients were positive for anti-CCP antibodies. Additionally, 82.5 % of RA patients and 42 % of COPD patients were positive for RF. Among RA patients, levels of anti-CCP antibodies were higher among smokers than among nonsmokers (242.7 ± 128.3 vs. 68.1 ± 112.1, P < 0.001). COPD patients had low titers of RF but were negative for anti-CCP antibodies. The presence of anti-CCP antibodies was a reliable serologic marker in RA diagnosis and was associated with cigarette smoking.
Similar content being viewed by others
References
Barra L, Pope J, Bessette L, Haraoui B, Bykerk V (2011) Lack of seroconversion of rheumatoid factor and anti-cyclic citrullinated peptide in patients with early inflammatory arthritis: a systematic literature review. Rheumatology (Oxford) 50:311–316
Szodoray P, Szabo Z, Kapitany A et al (2010) Anti-citrullinated protein/peptide autoantibodies in association with genetic and environmental factors as indicators of disease outcome in rheumatoid arthritis. Autoimmun Rev 9:140–143
Wiik AS, van Venrooij WJ, Pruijn GJ (2010) All you wanted to know about anti-CCP but were afraid to ask. Autoimmun Rev 10:90–93
Kokkonen H, Mullazehi M, Berglin E et al (2011) Antibodies of IgG, IgA and IgM isotypes against cyclic citrullinated peptide precede the development of rheumatoid arthritis. Arthr Res Ther 13:R13
Rantapaa-Dahlqvist S, de Jong BA, Berglin E et al (2003) Antibodies against cyclic citrullinated peptide and IgA rheumatoid factor predict the development of rheumatoid arthritis. Arthr Rheum 48:2741–2749
Scott DL, Wolfe F, Huizinga TW (2010) Rheumatoid arthritis. Lancet 376:1094–1108
Svard A, Kastbom A, Soderlin MK, Reckner-Olsson A, Skogh T (2011) A comparison between IgG- and IgA-class antibodies to cyclic citrullinated peptides and to modified citrullinated vimentin in early rheumatoid arthritis and very early arthritis. J Rheumatol 38:1265–1272
Goeldner I, Skare TL, de Messias Reason IT, Nisihara RM, Silva MB, da Rosa Utiyama SR (2011) Association of anticyclic citrullinated peptide antibodies with extra-articular manifestations, gender, and tabagism in rheumatoid arthritis patients from southern Brazil. Clin Rheumatol 30:975–980
Young KA, Deane KD, Derber LA et al. (2013) Relatives without rheumatoid arthritis show reactivity to anti-citrullinated protein/peptide antibodies which are associated with arthritis-related traits: studies of the etiology of rheumatoid arthritis. Arthr Rheum 65:1995–2004
Burr ML, Viatte S, Bukhari M et al (2012) Long-term stability of anti-cyclic citrullinated peptide antibody status in patients with early inflammatory polyarthritis. Arthr Res Ther 14:R109
Lima I, Santiago M (2010) Antibodies against cyclic citrullinated peptides in infectious diseases—a systematic review. Clin Rheumatol 29:1345–1351
Bang SY, Lee KH, Cho SK, Lee HS, Lee KW, Bae SC (2010) Smoking increases rheumatoid arthritis susceptibility in individuals carrying the HLA-DRB1 shared epitope, regardless of rheumatoid factor or anti-cyclic citrullinated peptide antibody status. Arthr Rheum 62:369–377
Mahdi H, Fisher BA, Kallberg H et al (2009) Specific interaction between genotype, smoking and autoimmunity to citrullinated alpha-enolase in the etiology of rheumatoid arthritis. Nat Genet 41:1319–1324
Pistelli R, Ferrara L, Misuraca C, Bustacchini S (2011) Practical management problems of stable chronic obstructive pulmonary disease in the elderly. Curr Opin Pulm Med 17(Suppl 1):S43–S48
Brusselle GG, Joos GF, Bracke KR (2011) New insights into the immunology of chronic obstructive pulmonary disease. Lancet 378:1015–1026
Tsoumakidou M, Tzanakis N, Kyriakou D, Chrysofakis G, Siafakas NM (2004) Inflammatory cell profiles and T-lymphocyte subsets in chronic obstructive pulmonary disease and severe persistent asthma. Clin Exp Allergy 34:234–240
Vaguliene N, Zemaitis M, Lavinskiene S, Miliauskas S, Sakalauskas R (2013) Local and systemic neutrophilic inflammation in patients with lung cancer and chronic obstructive pulmonary disease. BMC Immunol 14:36
Kilsgard O, Andersson P, Malmsten M et al (2012) Peptidylarginine deiminases present in the airways during tobacco smoking and inflammation can citrullinate the host defense peptide LL-37, resulting in altered activities. Am J Respir Cell Mol Biol 46:240–248
Reynisdottir G, Karimi R, Joshua V et al (2013) Structural lung changes and local anti-citrulline immunity are early features of anti citrullinated-proteins antibodies positive rheumatoid arthritis. Arthr Rheum
Wood AM, de Pablo P, Buckley CD, Ahmad A, Stockley RA (2011) Smoke exposure as a determinant of autoantibody titre in alpha(1)-antitrypsin deficiency and COPD. Eur Respir J 37:32–38
Newkirk MM, Mitchell S, Procino M et al (2012) Chronic smoke exposure induces rheumatoid factor and anti-heat shock protein 70 autoantibodies in susceptible mice and humans with lung disease. Eur J Immunol 42:1051–1061
Ruiz-Esquide V, Gomara MJ, Peinado VI et al (2012) Anti-citrullinated peptide antibodies in the serum of heavy smokers without rheumatoid arthritis. A differential effect of chronic obstructive pulmonary disease? Clin Rheumatol 31:1047–1050
Fischer A, Solomon JJ, du Bois RM et al (2012) Lung disease with anti-CCP antibodies but not rheumatoid arthritis or connective tissue disease. Respir Med 106:1040–1047
Klareskog L, Stolt P, Lundberg K et al (2006) A new model for an etiology of rheumatoid arthritis: smoking may trigger HLA-DR (shared epitope)-restricted immune reactions to autoantigens modified by citrullination. Arthr Rheum 54:38–46
Makrygiannakis D, Hermansson M, Ulfgren AK et al (2008) Smoking increases peptidylarginine deiminase 2 enzyme expression in human lungs and increases citrullination in BAL cells. Ann Rheum Dis 67:1488–1492
Kallberg H, Padyukov L, Plenge RM et al (2007) Gene-gene and gene-environment interactions involving HLA-DRB1, PTPN22, and smoking in two subsets of rheumatoid arthritis. Am J Hum Genet 80:867–875
Michou L, Teixeira VH, Pierlot C et al (2008) Associations between genetic factors, tobacco smoking and autoantibodies in familial and sporadic rheumatoid arthritis. Ann Rheum Dis 67:466–470
Oliveira RD, Junta CM, Oliveira FR, Silva LM, Donadi EA, Louzada-Junior P (2008) Share epitope, citrullinated cyclic peptide antibodies and smoking in Brazilian rheumatoid arthritis patients. Clin Rev Allergy Immunol 34:32–35
Klareskog L, Padyukov L, Alfredsson L (2007) Smoking as a trigger for inflammatory rheumatic diseases. Curr Opin Rheumatol 19:49–54
Fan LY, He DY, Wang Q et al (2012) Citrullinated vimentin stimulates proliferation, pro-inflammatory cytokine secretion, and PADI4 and RANKL expression of fibroblast-like synoviocytes in rheumatoid arthritis. Scand J Rheumatol 41:354–358
Vignola MB, Davila S, Cremonezzi D, Simes JC, Palma JA, Campana VR (2012) Evaluation of inflammatory biomarkers associated with oxidative stress and histological assessment of magnetic therapy on experimental myopathy in rats. Electromagn Biol Med 31:320–332
Jonsson T, Thorsteinsson J, Valdimarsson H (1998) Does smoking stimulate rheumatoid factor production in non-rheumatic individuals? APMIS 106:970–974
Hayahara C, Ikeda K, Sakanishi Y, Ota T (2010) Incidence of serum rheumatoid factors in elder non-rheumatic individuals. Rinsho Byori 58:211–215
Korpilahde T, Heliovaara M, Knekt P, Marniemi J, Aromaa A, Aho K (2004) Smoking history and serum cotinine and thiocyanate concentrations as determinants of rheumatoid factor in non-rheumatoid subjects. Rheumatology (Oxford) 43:1424–1428
Nielsen SF, Bojesen SE, Schnohr P, Nordestgaard BG (2012) Elevated rheumatoid factor and long term risk of rheumatoid arthritis: a prospective cohort study. BMJ 345:e5244
Masdottir B, Jonsson T, Manfredsdottir V, Vikingsson A, Brekkan A, Valdimarsson H (2000) Smoking, rheumatoid factor isotypes and severity of rheumatoid arthritis. Rheumatology (Oxford) 39:1202–1205
Cader MZ, Filer AD, Buckley CD, Raza K (2010) The relationship between the presence of anti-cyclic citrullinated peptide antibodies and clinical phenotype in very early rheumatoid arthritis. BMC Musculoskelet Disord 11:187
Acknowledgments
This study is supported by the Taichung Armed-Forces General Hospital (Grant No. 101-05). We also thank Miss Tzi-Yi Wu for her professional design.
Conflict of interest
The author has no conflicts of interest to declare.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Yang, DH., Tu, CC., Wang, SC. et al. Circulating anti-cyclic citrullinated peptide antibody in patients with rheumatoid arthritis and chronic obstructive pulmonary disease. Rheumatol Int 34, 971–977 (2014). https://doi.org/10.1007/s00296-013-2926-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00296-013-2926-6