Abstract
Recently, it has been found that some lupus patients may have anti-cyclic citrullinated peptide antibodies (anti-CCP), although the clinical significance of such finding is not well established. Systemic lupus erythematosus (SLE) patients may have joint complaints that are very similar to those observed in rheumatoid arthritis (RA). In early stages of disease, this form of arthritis can be difficult to differentiate from RA, so it is not rare that some SLE patients are initially misdiagnosed to have this disease. This study aims to investigate the prevalence of anti-CCP in SLE patients from Southern Brazil and its association with clinical and serological profiles. One hundred nine SLE patients were studied for anti-CCP and compared with data of 156 RA patients and 100 healthy volunteers. Comparison of clinical and autoantibody profile of anti-CCP-positive and anti-CCP-negative SLE patients was done. All SLE patients positive of anti-CCP were submitted to hand and feet X-rays. Anti-CCP was positive in 15 of 109 SLE patients, and one of them had confirmed the diagnosis of rhupus. This prevalence was significantly higher than in healthy controls (p = 0.0004) and lower than in RA patients (p < 0.0001). No relationship could be found with clinical profile, including joint complaints. SLE patients with anti-CCP had higher prevalence of anti-Ro (p = 0.02) and anti-La (p = 0.004) autoantibodies, in comparison with those negative to anti-CCP. We found that 13.7 % of Brazilian patients with SLE have positive anti-CCP. Patients with anti-CCP showed higher prevalence of anti-Ro and anti-La autoantibodies than those negative for anti-CCP. Only a careful and prolonged follow-up will reveal the real clinical value of these markers in each patient individually.
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References
Di Cesare PE, Valle CJD, Zuckerman JD (2004) Articular manifestations of Systemic lupus erythematosus. In: Lahita RG (ed) Systemic lupus erythematosus. Elsevier, San Diego, pp 1037–1063
Aitcheson CT, Peebles C, Joslin F, Tan EM (1980) Characteristics of antinuclear antibodies in rheumatoid arthritis. Arthritis Rheum 23:528–537
De La Torre IG, Miranda-Mendez L (1982) Studies of antinuclear antibodies in rheumatoid arthritis patients. J Rheumatol 42:603–606
Caspi D, Elkayan O, Eisinger M, Vardinon N, Yaron M, Burke M (2001) Clinical significance of low titer antinuclear antibodies in early rheumatoid arthritis: implications on the presentation and long term course of the disease. Rheumatol Int 20:43–47
Quismoro FP (1993) Other serologic abnormalities in SLE. In: Wallace DJ, Hahn B (eds) Dubois systemic lupus erythematosus. Lea & Febiger, Philadelphia, pp 264–276
Ioan-Facsinay A, Willemze A, Robinson DB, Peschken CA, Markland J, Van der Woude D et al (2008) Marked differences in fine specificity and isotype usage of the anti-citrullinated protein antibody in health and disease. Arthritis Rheum 58:3000–3008
Lee AN, Beck CE, Hall M (2008) Rheumatoid factor and anti-CCP antibodies in rheumatoid arthritis: a review. Clin Lab Sci 21:15–18
Nishimura K, Sugiyama D, Kogata Y, Tsuji G, Nakazawa T, Kawano S et al (2007) Meta-analysis: diagnostic accuracy of anti-cyclic citrullinated peptide antibody and rheumatoid factor for rheumatoid arthritis. Ann Intern Med 146:797–808
Avouac J, Gossec L, Dougados M (2006) Diagnostic and predictive value of anti-cyclic citrullinated protein antibodies in rheumatoid arthritis: a systematic literature review. Ann Rheum Dis 65:845–851
Singh U, Singh S, Singh NK, Verma PK, Singh S (2011) Anti cyclic citrullinated peptide autoantibodies in systemic lupus erythematosus. Rheumatol Int 31:765–767
Zhao Y, Li J, Li X, Li L, Li Z (2009) What can we learn from the presence of anti-cyclic citrullinated peptide antibodies in systemic lupus erythematosus? Joint Bone Spine 76:501–507
Qing Y-F, Zhang Q-B, Zhou J-G, Yuan G-H, Wei J, Xing Y et al (2009) The detecting and clinical value of anti cyclic citrullinated peptide antibodies in patients with systemic lupus erythematosus. Lupus 18:713–717
Kakumanu P, Sobel ES, Narain S, Akaogi J, Yamasaki Y, Segal MS et al (2009) Citrulline dependence of anti cyclic citrullinated peptide antibodies in systemic lupus erythematosus as a marker of deforming/erosive arthritis. J Rheumatol 36:2682–2690
Damian-Abrego GN, Cabiedes J, Cabral AR (2008) Anti citrullinated peptide antibodies in lupus patients with or without deforming arthropathy. Lupus 17:300–304
Mediwake R, Isenberg DA, Schellekens GA, van Venrooij WJ (2001) Use of anti-citrullinated peptide and anti-RA33 antibodies in distinguishing erosive arthritis in patients with systemic lupus erythematosus and rheumatoid arthritis. Ann Rheum Dis 60:67–68
Taraborelli M, Inverardi F, Fredi M, Ceribelli A, Cavazzana I, Tincani A, Franceschini F (2012) Anti-cyclic citrullinated peptide antibodies in systemic lupus erythematosus patients with articular involvement: a predictive marker for erosive disease? Reumatismo 64:321–325
Hochberg MC (1997) Updating the American college of Rheumatology revised criteria for systemic lupus erythematosus. Arthritis Rheum 40:1725
Goeldner I, Skare TL, de Messias Reason IT, Nisihara RM, Silva MB, Utiyama SR (2010) Anti-Cyclic citrullinated peptide antibodies and rheumatoid factor in rheumatoid arthritis patients and relatives from Brazil. Rheumatology 49:1590–1593
Fox RI (1997) Sjögren’s syndrome. Controversies and progress. Clin Lab Med 17:431–444
Marinez JB, Valero JS, Bautista AJ, Restrepo JF, Matteson EL, Rondon F et al (2007) Erosive arthropathy: clinical variance in lupus erythematosus and association with anti CCP case series and review of the literature. Clin Exp Rheumatol 25:47–53
Skare TS, Nisihara RM, Silva RM, Munhoz da Silva DJ, Gameiro Silva MB, Utiyama SR (2011) Anti-cyclic citrullinated peptide antibodies in adult patients with juvenile idiopathic arthritis. Clin Rheumatol 17:421–423
Polimeni M, Feniman D, Skare TS, Nisihara RM (2012) Anticyclic citrullinated peptide antibodies in scleroderma patients. Clin Rheumatol 31:877–880
Alenius GM, Berglin E, Dalqvist SR (2006) Antibodies against cyclic cytrullinated peptide (CCP) in psoriatic patients with or without joint inflammation. Ann Rheum Dis 65:398–400
Senkpiehl I, Marget M, Wedler M, Jenisch S, Georgi J et al (2005) HLA-DRB1 and anti-cyclic citrullinated peptide antibody production in rheumatoid arthritis. Int Arch Allergy Immunol 137:315–318
Kakumanu P, Sobel ES, Narain S, Jun UL, Akogi K, Yamasaki Y et al (2009) Citrulline dependence of anti cyclic citrullinated peptide antibodies in systemic lupus erythematosus as a marker of deforming/erosive arthritis. J Rheumatol 36:2682–2690
Panush RS, Edwards NL, Longley S, Webster E (1988) Rhupus syndrome. Arch Intern Med 148:1633–6
Nielen MM, van Schaardenburg D, Reesink HW, van de Stadt RJ, Van der Horst-Bruinsma IE, de Kpning MH et al (2004) Specific autoantibodies precede the symptoms of rheumatoid arthritis: a study of serial measurements in blood donors. Arthritis Rheum 50:380–386
Majka DS, Deane KD, Parrish LA, Lazar AA, Barón AE, Walker CM et al (2008) Duration of preclinical RA-related autoantibody positivity increases in subjects with older age at time of disease diagnosis. Ann Rheum Dis 67:801–807
Chibnik LB, Mandi LA, Costendaber KH, Shur PH, Karlson EW (2009) Comparison of threshold cut-points and continuous measures of anti-CCP antibodies in predicting future RA. J Rheumatol 36:706–711
Lee DM, Pjillips R, Hagan EM, Chibnik LB, Costenbader KH, Shur PH (2009) Quantifying anti-cyclic citrullinated peptide titres: clinical utility and association with tobacco exposure in patients with rheumatoid arthritis. Ann Rheum Dis 68:201–208
Cavazzana I, Francheschini F, Quinzanini M, Manera C, Del Papa N, Maglione W et al (2006) Anti Ro/SS-A antibodies in rheumatoid arthritis. Clinical and immunological associations. Clin Exp Rheumatol 24:59–64
Franchescini F, Cavazzana L (2005) Anti-Ro/SSA and La/SSB antibodies. Autoimmunity 38:55–63
Schneeberger E, Citera G, Heredia M, Cocco JM (2008) Clinical significance of anti- Ro antibodies in rheumatoid arthritis. Clin Rheumatol 27:517–519
Zanlorenzi L, Azevedo LOP, Silva MB, Skare TL (2012) Anti-Ro in rheumatoid arthritis. Acta Rheum Port 37:149–151
Mohammed K, Pope J, Riche N, Brintnell W, Cairns E, Coles R et al (2009) Association of severe inflammatory polyarthritis in primary sjögren’s syndrome: clinical, serological and HLA analysis. J Rheumatol 36:1937–1942
Verpoort KN, van Gaalen FA, Mil AHMH, Schreuder GMT, Breedveld FCM, Huizinga TWJ et al (2005) Association of HLA-DR3 with anti cyclic citrullinated peptide antibody-negative rheumatoid arthritis. Arthritis Rheum 52:3058–3062
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Skare, T.L., Nisihara, R., Barbosa, B.B. et al. Anti-CCP in systemic lupus erythematosus patients: a cross sectional study in Brazilian patients. Clin Rheumatol 32, 1065–1070 (2013). https://doi.org/10.1007/s10067-013-2213-7
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DOI: https://doi.org/10.1007/s10067-013-2213-7