Evaluation of clinical and laboratory findings of 147 patients with systemic lupus erythematosus: The relationship between anti-CCP and arthritis

Öz

Aim: Anti-cyclic citrullinated peptide antibodies (Anti-CCP) is considered as a novel marker in the assessment of rheumatoid disorders. Some studies have emphasized the importance of anti-CCP in indicating erosive arthropathy in Systemic Lupus Erythematosus (SLE), like Rheumatoid Arthritis (RA). These studies have reported that the chance of erosive arthritis development is significantly increased in anti-CCP-positive patients. This study aimed to investigate the relationship between anti-CCP and arthritis along with other clinical and laboratory parameters in patients with SLE.

Methods: A total of 147 SLE patients who had been admitted to Kocaeli University Medical Faculty, Department of Internal Medicine, Division of Rheumatology between January 2001 and October 2015 were included in this retrospective study. SLE diagnosis was verified according to American College of Rheumatology (ACR) and/or The Systemic Lupus Erythematosus International Collaborating Clinics (SLICC) criteria. Patients whose diagnosis was not definite and not having anti-CCP were excluded.

Results: Female/male ratio was found as 5.6, and the mean age was calculated as 43.9±11.85 years. The mean follow-up period was 73.3±44.97 months. Anti-CCP was found to be positive in ten patients whereas arthritis was found to be present in 100 patients. Anti-CCP was positive in seven patients with arthritis. RF (Rheumatoid Factor) was found as positive in 50 patients of whom 40 had arthritis. A relationship was found between Anti-CCP and RF. There was no relationship between anti-CCP and arthritis. 

Conclusions: Anti-CCP has been reported to be significantly related to arthritis and other characteristics of rheumatoid disorders, particularly RA in several studies. There are conflicting results about the relationship between anti-CCP and arthritis in patients with SLE. These conflicting results may be derived from different subtypes of anti-CCP (citrulline-dependent), different cut-off values, and characteristics of the patient population. We did not observe any relationship between the Anti-CCP and arthritis.

Anahtar Kelimeler

• Arthritis,Systemic lupus erythematosus,Anti-cyclic citrullinated peptide antibodies

Sistemik lupus eritematozuslu 147 hastanın klinik ve laboratuvar bulgularının değerlendirilmesi: Anti CCP ile artrit arasındaki ilişkinin incelenmesi

Öz

Giriş: Anti-siklik sitrülline peptid antikorları (Anti-CCP), romatoid hastalıkların değerlendirilmesinde yeni bir belirteç olarak kabul edilir. Bazı çalışmalar Romatoid Artrit (RA) gibi sistemik lupus eritematozus’da (SLE) eroziv artropatinin gösterilmesinde Anti-CCP'nin önemini vurgulamıştır. Bu çalışmalar, Anti-CCP pozitif hastalarda eroziv artrit gelişme ihtimalinin anlamlı şekilde arttığını bildirmiştir. Bu çalışmanın amacı, SLE'li hastalarda Anti-CCP ve artrit ile diğer klinik ve laboratuvar parametreleri arasındaki ilişkiyi araştırmaktır. 

Yöntemler: Ocak 2001 - Ekim 2015 tarihleri arasında Kocaeli Üniversitesi Tıp Fakültesi, İç Hastalıkları Anabilim Dalı, Romatoloji Bilim Dalı’na başvuran SLE'li toplam 147 hasta çalışmaya dahil edildi. SLE tanısı Amerikan Romatoloji Birliği (ACR) ve / veya Sistemik Lupus Eritematozus Uluslararası İşbirliği Klinikleri (SLICC) kriterleri ile doğrulandı. Kesin olmayan ve Anti-CCP si olmayan hastalar çalışma dışı bırakıldı. 

Bulgular: Kadın / erkek oranı 5,6, yaş ortalaması 43,9±11,85 idi. Ortalama takip süresi 73,3±44,97 aydı. 10 hastada anti-CCP pozitifti, 100 hastada ise artrit vardı. Artritli hastaların yedisinde Anti-CCP pozitifti. RF (Romatoid Faktör), 40’ı artritli olan 50 hastada pozitif bulundu. Anti-CCP ile RF arasında bir ilişki olduğu tespit edildi. Anti-CCP ile artrit arasında ise ilişki yoktu. 

Sonuçlar: Bazı çalışmalarda, özellikle RA gibi romatolojik hastalıkların artrit ve diğer özelliklerinin Anti-CCP ile bağlantısı olduğu rapor edilmiştir. SLE'li hastalarda anti-CCP ile artrit arasındaki ilişkiyle ilgili çelişkili sonuçlar vardır. Bu çelişkili sonuçlar farklı Anti-CCP alt tiplerden (sitrülin bağımlı), farklı cut-off değerlerinden ve hasta popülasyonunun özelliklerinden kaynaklanabilir. Anti-CCP ile artrit arasında herhangi bir ilişki gözlemlemedik.

Anahtar Kelimeler

• Sistemik lupus eritematozus,Anti-siklik sitrülline peptid antikorları,Artrit

Kaynakça

1. 1. Liu Z, Davidson A. Taming lupus-a new understanding of pathogenesis is leading to clinical advances. Nat Med. 2012;18(6): 871-82.
2. 2. Dema B, Charles N. Advances in mechanisms of systemic lupus erythematosus. Discov Med. 2014;17(95):247-55.
3. 3. Osio-Salido E, Manapat-Reyes H. Epidemiology of systemic lupus erythematosus in Asia. Lupus. 2010;19(12):1365-73.
4. 4. Clark MR, Liu L, Clarkson SB, Ory PA, Goldstein IM. An abnormality of the gene that encodes neutrophil Fc receptor III in a patient with systemic lupus erythematosus. J Clin Invest. 1990;86(1):341-6.
5. 5. Bizzaro N, Mazzanti G, Tonutti E, Villalta D, Tozzoli R. Diagnostic accuracy of the anti-citrulline antibody assay for rheumatoid arthritis. ClinChem. 2001;47(6):1089-93.
6. 6. Kastbom A, Strandberg G, Lindroos A, Skog T. Anti-CCP antibody test predicts the disease course during 3 years in early rheumatoid arthritis (the Swedish TIRA project). Ann Rheum Dis. 2004;63(9):1085-9.
7. 7. van Boekel MA, Vossenaar ER, van den Hoogen FH, van VenrooijWJ. Autoantibody systems in rheumatoid arthritis: specificity, sensitivity and diagnostic value. Arthritis Res. 2002;4(2):87-93.
8. 8. Kasper D, Fauci A, Hauser S, Longo D. Jameson JL, Loscalzo J. Harrison's principles of internal medicine. 19th edition.ed. 2 volumes. 2015; xxxviii, pp. 2770 I-200.

9. 9. Choi SW, Lim MK, Shin DH, Park JJ, Shim SC. Diagnostic Performances of Anti-Cyclic Citrullinated Peptides Antibody and Antifilaggrin Antibody in Korean Patients with Rheumatoid Arthritis. J Korean Med Sci. 2005;20(3):473-8.
10. 10. Schellekens GA, de Jong BA, van den Hoogen FH, van de Putte LB, van Venrooij WJ. Citrulline is an essential constituent of antigenic determinants recognized by rheumatoid arthritis-specific autoantibodies. J Clin Invest. 1998;101(1):273-81.
11. 11. Avouac J, Gossec L, Dougados M. Diagnostic and predictive value of anti-cyclic citrullinated protein antibodies in rheumatoid arthritis: a systematic literature review. Ann Rheum Dis. 2006;65(7):845-51.
12. 12. Matsui T, Shimada K, Ozawa N, Hayakawa H, Hagiwara F, Nakayama H, et al. Diagnostic utility of anti-cyclic citrullinated peptide antibodies for very early rheumatoid arthritis. J Rheumatol. 2006;33(12):2390-7.
13. 13. Sauerland U, Becker H, Seidel M, Schotte H, Willeke P, Schorat A, et al. Clinical utility of the anti-CCP assay: experiences with 700 patients. Ann N Y Acad Sci. 2005;1050:314-8.
14. 14. Takasaki Y, Yamanaka K, Takasaki C, Matsushita M, Yamada H, Nawata M, et al., Anticycliccitrullinated peptide antibodies in patients with mixed connective tissue disease. Mod Rheumatol. 2004;14(5):367-75.
15. 15. Vasishta A. Diagnosing early-onset rheumatoid arthritis: the role of anti-CCP antibodies. Am Clin Lab. 2002;21(7):34-6.
16. 16. Qing YF, Zhang QB, Zhou JG, Yuan GH, Wei J, Xing Y, et al. The detecting and clinical value of anti-cyclic citrullinated peptide antibodies in patients with systemic lupus erythematosus. Lupus. 2009;18(8):713-7.
17. 17. Kakumanu P, Sobel ES, Narain S, Li Y, Akaogi J, Yamasaki Y, et al. Citrulline dependence of anti-cyclic citrullinated peptide antibodies in systemic lupus erythematosus as a marker of deforming/erosive arthritis. J Rheumatol. 2009;36(12):2682-90.
18. 18. Damian-Abrego GN, Cabiedes J, Cabral AR. Anti-citrullinated peptide antibodies in lupus patients with or without deforming arthropathy. Lupus. 2008;17(4):300-4.
19. 19. Amezcua-Guerra LM, Springall R, Marquez-Velasco R, Gómez-García L, Vargas A, Bojalil R, et al. Presence of antibodies against cyclic citrullinated peptides in patients with 'rhupus': a cross-sectional study. Arthritis Res Ther. 2006;8(5):R144.
20. 20. Amezcua-Guerra LM, Marquez-Velasco R, Bojalil R. Erosive arthritis in systemic lupus erythematosus is associated with high serum C-reactive protein and anti-cyclic citrullinated peptide antibodies. Inflamm Res. 2008;57(12):555-7.
21. 21. Chan MT, Owen P, Dunphy J, Cox B, Carmichael C, Korendowych E, et al. Associations of erosive arthritis with anti-cyclic citrullinated peptide antibodies and MHC Class II alleles in systemic lupus erythematosus. J Rheumatol. 2008; 35(1):77-83.
22. 22. Martinez JB, Valero JS, Bautista AJ, Restrepo JF, Matteson EL, Rondon F, et al. Erosive arthropathy: clinical variance in lupus erythematosus and association with anti-CCP case series and review of the literature. Clin Exp Rheumatol. 2007;25(1):47-53.
23. 23. Mediwake R, Isenberg DA, Schellekens GA, van Venrooij WJ, et al. 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. 2001;60(1):67-8.
24. 24. van Vugt RM, Derksen RH, Kater L, Bijlsma JW, et al. Deforming arthropathy or lupus and rhupus hands in systemic lupus erythematosus. Ann Rheum Dis. 1998;57(9):540-4.
25. 25. Cervera R, Khamashta MA, Font J, Sebastiani GD, Gil A, Lavilla P, et al. Morbidity and mortality in systemic lupus erythematosus during a 10-year period: a comparison of early and late manifestations in a cohort of 1,000 patients. Medicine (Baltimore). 2003;82(5):299-308.
26. 26. Cronin ME. Musculoskeletal manifestations of systemic lupus erythematosus. Rheum Dis Clin North Am. 1988;14(1):99-116.
27. 27. Tani C, D'Aniello D, DelleSedie A, Carli L, Cagnoni M, Possemato N, et al. Rhupus syndrome: assessment of its prevalence and its clinical and instrumental characteristics in a prospective cohort of 103 SLE patients. Autoimmun Rev. 2013;12(4):537-41.
28. 28. Vannini A, Cheung K, Fusconi M, Stammen-Vogelzangs J, Drenth JP, Dall'Aglio AC, et al. Anti-cyclic citrullinated peptide positivity in non-rheumatoid arthritis disease samples: citrulline-dependent or not? Ann Rheum Dis. 2007;66(4):511-6.
29. 29. Spronk PE, ter Borg EJ, Kallenberg CG. Patients with systemic lupus erythematosus and Jaccoud's arthropathy: a clinical subset with an increased C reactive protein response? Ann Rheum Dis. 1992;51(3):358-61.
30. 30. Alarcón-Segovia D, Abud-Mendoza C, Diaz-Jouanen E, Iglesias A, De los Reyes V, Hernández-Ortiz J, et al. Deforming arthropathy of the hands in systemic lupus erythematosus. J Rheumatol. 1988;15(1): 65-9.
31. 31. Esdaile JM, Danoff D, Rosenthall L, Gutkowski A. Deforming arthritis in systemic lupus erythematosus. Ann Rheum Dis. 1981;40(2):124-6.
32. 32. Ball EM, Tan AL, Fukuba E, McGonagle D, Grey A, Steiner G, et al. A study of erosive phenotypes in lupus arthritis using magnetic resonance imaging and anti-citrullinated protein antibody, anti-RA33 and RF autoantibody status. Rheumatology (Oxford). 2014;53(10):1835-43.