The clinic importance of bilirubin parameters in ankylosing spondylitis: Case control study

Yıl 2018, Cilt: 2 Sayı: 3, 330 - 333, 01.09.2018

Tuba Tülay Koca , Gözde Yıldırım Çetin Hasan Göğebakan , Vedat Nacitarhan

https://doi.org/10.28982/josam.441711

Öz

Aim: Ankylosing spondylitis (AS) is a chronic disease featuring axial changes, peripheral arthritis and systemic involvement. AS is not only characterized by the strongest genetic contribution for any complex rheumatological disease but is also influenced by environmental and immunological factors. Various proinflammatory cytokines such as tumor necrosis factor (TNF), interleukin- (IL-) 1, IL-6, IL17/28 are probably involved in AS pathogenesis. Recent years IL -23 / IL-17 pathway in the disease pathogenesis has been shown. Bilirubin (Bb) was known to be the end product of hem catabolic pathway, but it was the subject of various studies with antioxidant, anti-inflammatory and immunomodulatory properties in the last decade. Here, the clinic importance of serum Bb parameters in AS patients has been analyzed.

Methods: The study designed as case-control. One hundred (N=100) patients with axial AS diagnosed by 2010 Assesment in Ankylosing Spondylitis International Society (ASAS) Classification Criteria were included to the study. Control group was consisted of 75 patients of similar age, gender and BMI. Participants' age, gender, body mass index (BMI), disease acitivity scores and laboratory data were recorded from the hospital data. Disease activity evaluated by Bath Ankylosing spondylitis disease activity index (BASDAI), Bath Ankylosing spondylitis functional index (BASFI) and Ankylosing spondylitis disease activity score-C-reactive protein (ASDAS_CRP). For these three scores, automatic calculation formulas were used on Internet. ASDAS_CRP>3.5 were accepted as cut-off value for high disease activity. Serum direct Bb, indirect Bb, total Bb, aspartat aminotransferase (AST), alanin aminotransferase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), gamma glutamyl transferase (GGT), amylase, lipase, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) values were recorded from the hospital records.

Results: The study included 100 AS patients at mean age of 37.9 ± 12 years, 75 controls at mean age of 39.2 ± 5.2 years. There was no significant difference between the two groups in terms of age (p = 0.12), gender (p = 0.32), and BMI (p = 0.067). In the AS group, ESR (p< 0.001), CRP (p < 0.001), uric acid (p<0.001) was significantly higher whereas direct Bb (P = 0.016) were significantly lower than controls. In correlation analysis, Bb parameters and disease activity parameters were negatively correlated with each other. When we divided the group according to ASDAS_CRP> 3.5, direct Bb (p = 0.020), total Bb (p = 0.029) and AST (p = 0.004) were significantly lower in high activity group (N = 25) and ESR (p = 0.000) was significantly higher.

Conclusion: The direct Bb in patients with AS were found significantly low and negatively correlated with disease activity, this supports the role of oxidative stress in AS disease pathogenesis. Bb can be used as a biomarker in diagnosis and follow up in AS disease.

Anahtar Kelimeler

Ankylosing spondylitis, Bilirubin, Inflammation, Oxidative stress

Ankilozan spondilitte bilirubin parametrelerinin klinik önemi: Vaka kontrol çalışması

Öz

Amaç: Ankilozan spondilit (AS) aksiyal değişiklikler, periferik artrit ve sistemik tutulum içeren kronik bir hastalıktır. AS herhangi bir komplike romatizmal hastalık gibi sadece en güçlü genetik katkı ile karakterize edilmez, aynı zamanda çevresel ve immünolojik faktörlerden de etkilenir. Tümör nekroz faktörü (TNF), interlökin- (IL-) 1, IL-6, IL17 / 28 gibi çeşitli proinflamatuar sitokinler muhtemelen AS patogenezinde rol oynar. Son yıllarda hastalık patogenezinde IL-23 / IL-17 yolu gösterilmiştir. Bilirubin (Bb) hem katabolik yolun son ürünüdür hem de son on yılda antioksidan, antienflamatuar ve immünmodülatör özellikleri olan çeşitli çalışmaların konusu olmuştur. Burada AS hastalarında serum Bb parametrelerinin klinik önemi analiz edilmiştir.

Yöntemler: Çalışma vaka-kontrol olarak planlandı. Uluslar arası Ankilozan Spondilit Topluluğu 2010 Sınıflandırma Kriterleri'ne göre (ASAS) aksiyal AS tanısı almış 100 hasta (N = 100) çalışmaya dahil edildi. Kontrol grubu benzer yaş, cinsiyet ve VKİ olan 75 kişiden oluşmaktaydı. Katılımcıların yaş, cinsiyet, vücut kitle indeksi (BMI), hastalık skoru puanları ve laboratuvar verileri hastane verilerinden kaydedildi. Hastalık aktivitesi Bath Ankilozan Spondilit Hastalığı Aktivite İndeksi (BASDAI), Bath Ankilozan Spondilit Fonksiyonel İndeks (BASFI) ve Ankilozan Spondilit Hastalığı Aktivite skoru-C-reaktif protein (ASDAS_CRP) ile değerlendirildi. Bu üç puan için, internette otomatik hesaplama formülleri kullanıldı. ASDAS_CRP> 3,5 yüksek hastalık aktivitesi için eşik değer olarak kabul edildi. Serum direkt Bb, indirekt Bb, total Bb, aspartat aminotransferaz (AST), alanin aminotransferaz (ALT), alkalen fosfataz (ALP), laktat dehidrojenaz (LDH), gama glutamil transferaz (GGT), amilaz, lipaz, eritrosit sedimentasyon hızı (ESR) ve C-reaktif protein (CRP) değerleri hastane kayıtlarından kaydedildi.

Bulgular: Çalışmaya yaş ortalaması 37,9 ± 12 yıl olan 100 AS hastası, yaş ortalaması 39,2 ± 5,2 yıl olan 75 kontrol alındı. İki grup arasında yaş (p = 0.12), cinsiyet (p = 0.32) ve VKİ (p = 0.067) açısından anlamlı fark yoktu. AS grubunda ESR (p < 0.001), CRP (p< 0.001), Bb (p = 0.016) anlamlı düşük; ürik asit (p< 0.001) kontrollerden anlamlı olarak yüksek bulundu.

Korelasyon analizinde, Bb parametreleri ve hastalık aktivite parametreleri birbirleriyle negatif korelasyon göstermiştir. ASDAS_CRP> 3,5'e göre gruplandırıldığında, direkt Bb (p = 0,020), total Bb (p = 0,029) ve AST (p = 0,004) yüksek aktivite grubunda (N = 25) anlamlı düşük; ESR (p <0,001) anlamlı olarak daha yüksekti.

Sonuç: AS'li hastalarda direk Bb, hastalık aktivitesi ile negatif ilişkili ve düşük idi, bu sonuç AS hastalık patogenezinde oksidatif stresin rolünü desteklemektedir. Direk Bb, AS hastalığında tanı ve izlemede biyobelirteç olarak kullanılabilir.

Anahtar Kelimeler

Ankilozan spondilit, Bilirubin, İnflamasyon, Oksidatif stres

Kaynakça

• 1. Smith JA. Update on ankylosing spondylitis: current concepts in pathogenesis. Curr Allergy Asthma Rep. 2015 Jan;15(1):489. doi: 10.1007/s11882-014-0489-6.
• 2. Jethwa H, Bowness P. The interleukin (IL)-23/IL-17 axis in ankylosing spondylitis: new advances and potentials for treatment. Clin Exp Immunol. 2016 Jan;183(1):30-6. doi: 10.1111/cei.12670.
• 3. Shibama S, Ugajin T, Yamaguchi T, Yokozeki H. Bilirubin oxidation derived from oxidative stress is associated with disease severity of atopic dermatitis in adults. Clin Exp Dermatol. 2018 Jun 4. doi: 10.1111/ced.13674.
• 4. Vanaki N, Aslani S, Jamshidi A, Mahmoudi M. Role of innate immune system in the pathogenesis of ankylosing spondylitis. Biomed Pharmacother. 2018 May 28;105:130-43. doi: 10.1016/j.biopha.2018.05.097.
• 5. Chyuan IT, Chen JY. Role of Interleukin- (IL-) 17 in the Pathogenesis and Targeted Therapies in Spondyloarthropathies. Mediators Inflamm. 2018 Feb 12;2018:2403935. doi: 10.1155/2018/2403935.
• 6. O'Rielly DD, Zhai G, Rahman P. Expression and Metabolomic Profiling in Axial Spondyloarthritis. Curr Rheumatol Rep. 2018 Jun 27;20(8):51. doi: 10.1007/s11926-018-0756-y.
• 7. Syrbe U, Baraliakos X. [Spondyloarthritis]. Z Rheumatol. 2018 May 16. doi:10.1007/s00393-018-0475-9. [Epub ahead of print] Review.
• 8. Yeremenko N, Paramarta JE, Baeten D. The interleukin-23/interleukin-17 immune axis as a promising new target in the treatment of spondyloarthritis. Curr Opin Rheumatol. 2014 Jul;26(4):361-70. doi: 10.1097/BOR.0000000000000069.
• 9. Rabelo CF, Baptista TSA, Petersen LE, Bauer ME, Keiserman MW, Staub HL. Serum IL-6 correlates with axial mobility index (Bath Ankylosing Spondylitis Metrology Index) in Brazilian patients with ankylosing spondylitis. Open Access Rheumatol. 2018 Apr 30;10:21-5. doi: 10.2147/OARRR.S130176.
• 10. Raychaudhuri SP, Raychaudhuri SK. IL-23/IL-17 axis in spondyloarthritis-bench to bedside. Clin Rheumatol. 2016 Jun;35(6):1437-41. doi:10.1007/s10067-016-3263-4.
• 11. Raychaudhuri SP, Deodhar A. The classification and diagnostic criteria of ankylosing spondylitis. J Autoimmun. 2014 Feb-Mar;48-49:128-33. doi: 10.1016/j.jaut.2014.01.015.
• 12. Dani C, Poggi C, Pratesi S. Bilirubin and oxidative stress in term and preterm infants. Free Radic Res. 2018 May 16:1-151. doi: 10.1080/10715762.2018.1478089.
• 13. Wei J, Zhao H, Fan G, Li J. Bilirubin treatment suppresses pulmonary inflammation in a rat model of smoke-induced emphysema. Biochem Biophys Res Commun. 2015 Sep 18;465(2):180-7. doi: 10.1016/j.bbrc.2015.07.133.
• 14. Jangi S, Otterbein L, Robson S. The molecular basis for the immunomodulatory activities of unconjugated Bb. Int J Biochem Cell Biol. 2013;45(12):2843-51. doi: 10.1016/j.biocel.2013.09.014.
• 15. Jangi S, Otterbein L, Robson S. The molecular basis for the immunomodulatory activities of unconjugated bilirubin. Int J Biochem Cell Biol. 2013 Dec;45(12):2843-51. doi: 10.1016/j.biocel.2013.09.014. Epub 2013 Oct 19.
• 16. Khan NM, Poduval TB. Immunomodulatory and immunotoxic effects of bilirubin: molecular mechanisms. J Leukoc Biol. 2011 Nov;90(5):997-1015. doi: 10.1189/jlb.0211070. Epub 2011 Aug 1.
• 17. Horsfall LJ, Rait G, Walters K, Swallow DM, Pereira SP, Nazareth I, et al. Serum bilirubin and risk of respiratory disease and death. JAMA. 2011;305(7):691–7.
• 18. Temme EH, Zhang J, Schouten EG, Kesteloot H. Serum bilirubin and 10-year mortality risk in a Belgian population. Cancer Causes Control. 2001;12(10):887–94.
• 19. Akboga MK, Canpolat U, Sahinarslan A, Alsancak Y, Nurkoc S, Aras D, Aydogdu S, Abaci A. Association of serum total bilirubin level with severity of coronary atherosclerosis is linked to systemic inflammation. Atherosclerosis. 2015 May;240(1):110-4. doi: 10.1016/j.atherosclerosis.2015.02.051
• 20. Zhou ZX, Chen JK, Hong YY, Zhou R, Zhou DM, Sun LY, et al. Relationship Between the Serum Total Bb and Inflammation in Patients With Psoriasis Vulgaris. J Clin Lab Anal. 2016;30(5):768-75. doi: 10.1002/jcla.21936. Epub 2016 Apr 7
• 21. Peng YF, Xie LQ, Xiang Y, Xu GD. Serum Bb and Their Association With C-Reactive Protein in Patients With Migraine. J Clin Lab Anal. 2016;30(6):982-5. doi: 10.1002/jcla.21967.
• 22. Dandekar A, Mendez R, Zhang K. Cross talk between ER stress, oxidative stress,and inflammation in health and disease. Methods Mol Biol. 2015;1292:205-14. doi: 10.1007/978-1-4939-2522-3_15.
• 23. Koca T, Arslan A, Çiledağ Özdemir F, Berk E. The importance of red cell distribution width and neutrophil-lymphocyte ratio as a new biomarker in rheumatoid arthritis. The European Research Journal, 2018. doi: 10.18621/eurj.376346
• 24. Koca TT. Does obesity cause chronic inflammation? The association between complete blood parameters with body mass index and fasting glucose. Pak J Med Sci. 2017 Jan-Feb;33(1):65-69. doi: 10.12669/pjms.331.11532.
• 25. Robinson AC, Teeling M, Casey EB. Hepatic function in ankylosing spondylitis. Ann Rheum Dis. 1983;42(5):550-552.
• 26. N J Sheehan, B M Slavin, P R Kind, and J A Mathews. Increased serum alkaline phosphatase activity in ankylosing spondylitis. Ann Rheum Dis. 1983;42(5):563–565.
• 27. Kim Y, Kang J, Kim GT. Prevalence of hyperuricemia and its associated factors in the general Korean population: an analysis of a population-based nationally representative sample. Clin Rheumatol. 2018 May 23. doi:10.1007/s10067-018-4130-2.