The Relationship Between Serum IL-17 and TNF-Alpha Levels and Disease Activity in Patients with Ankylosing Spondylitis

Abstract

Objective: Ankylosing spondylitis (AS) is a chronic inflammatory disease affecting the spine and sacroiliac joints. This study aimed to investigate the effects of IL-17 and TNF-α on the pathogenesis of AS as well as their association with disease activity and duration, treatment type, and initiation time. Methods: The study included 91 patients diagnosed with AS, 29 patients diagnosed with RA and 31 healthy volunteers. The serum levels of TNF-alpha and IL-17 were measured using an ELISA kit, while the patient files concurrently recorded levels of C- reactive protein (CRP), erythrocyte sedimentation rate (ESR), Bath Ankylosing Spondylitis Functional Index (BASFI), and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores. Results: 31.9% of AS patients received conventional treatment, while 68.1% received anti-TNF treatment. Significant differences were detected in interleukin-17 (IL-17) and tumor necrosis factor-alpha (TNF-α) levels among groups. RA patients had lower IL-17 levels compared to other groups (p: 0.012), and conventional treatment-receiving AS and RA patients had lower TNF-α levels compared to anti-TNF-receiving AS patients and healthy volunteers (p: 0.009). Significant differences were found in IL-17 and TNF- α levels between conventionally treated AS patients and healthy volunteers. No significant differences were found in IL-17 and TNF-α levels between anti-TNF treated AS patients and healthy volunteers. While there was no statistical difference in BASFI, 12 ESR, CRP, IL-17, and TNF-α levels between anti-TNF treated and conventionally treated AS patients, patients receiving anti-TNF treatment had lower BASDAI scores (p: 0.036). Conclusion: Biomarkers such as IL-17 and TNF-alpha facilitate monitoring treatment efficacy and determining patient-specific treatment options.

Keywords

• Ankylosing spondylitis
• Interleukin-17
• Tumor Necrosis Factor-alpha

Ankilozan Spondilit Hastalarında Serum IL-17 ve TNF-Alfa Düzeyi ile Hastalık Aktivitesi Arasındaki İlişki

Öz

Amaç: Ankilozan spondilit (AS), omurga ve sakroiliak eklemleri etkileyen kronik inflamatuar bir hastalıktır. Bu çalışma, IL-17 ve TNF-alfa'nın AS patogenezindeki etkisi, hastalık aktivitesi ve süresi, tedavi şekli ve başlama süresiyle ilişkisini incelemeyi amaçlamaktadır. Yöntemler: Bu çalışmaya AS tanısı alan 91 hasta, romatoid artrit (RA) tanısı alan 29 hasta ile 31 sağlıklı gönüllü dâhil edildi. Serum TNF-alfa ve IL-17 düzeyi elisa kiti kullanılarak ölçüldü eş zamanlı olarak hasta dosyalarında c-reaktif protein (CRP), sedimentasyon düzeyi ve Bath Ankilozan Spondilit Fonksiyonel İndeksi (BASFİ) - Bath ankilozan spondilit hastalık aktivite indeksi (BASDAI) skorları kaydedildi. Bulgular: AS hastalarının %31,9'u konvansiyonel tedavi alırken, %68,1'i anti-TNF tedavisi almıştır. İnterlökin-17 (IL-17) ve tümör nekroz faktör-alfa (TNF-α) düzeylerinde gruplar arasında anlamlı farklar tespit edilmiştir. RA hastalarında IL-17 düzeyleri diğer gruplardan daha düşük bulunurken (p= 0,012), konvansiyonel tedavi alan AS hastaları ve RA hastalarının TNF-α düzeyleri, anti-TNF alan AS hastaları ve sağlıklı gönüllülere göre daha düşük bulunmuştur (p: 0,009). Konvansiyonel tedavi alan AS hastaları ve sağlıklı gönüllüler arasında IL-17 ve TNF-α düzeylerinde anlamlı farklar bulunmuştur. Anti-TNF tedavi alan AS hastaları ve sağlıklı gönüllüler arasında ise IL-17 ve TNF-α düzeylerinde anlamlı fark bulunmamıştır. Anti-TNF tedavisi alan AS hastaları ile konvansiyonel tedavi alan AS hastaları arasında BASFI, ESR, CRP, IL- 12 17 ve TNF-α düzeylerinde istatistiksel fark bulunmazken, anti-TNF tedavisi alan hastaların BASDAI puanları daha düşük bulunmuştur (p: 0,036). Sonuç: IL-17 ve TNF-alfa gibi biyobelirteçler, tedavi etkinliğini izlemek için ve hastaya özgü tedavi seçeneklerini belirlemek için kolaylaştırıcı faktörlerdir.

Anahtar Kelimeler

• Ankilozan spondilit
• İnterlökin-17
• Tümör Nekrozis Faktör alfa

References

1. 1. Sieper J, Rudwaleit M, Khan MA, Braun J. Concepts and epidemiology of spondyloarthritis. Best practice & research Clinical rheumatology 2006; 20(3):401-17.
2. 2. Linden SVD, Valkenburg HA, Cats A. Evaluation of diagnostic criteria for ankylosing spondylitis. Arthritis & Rheumatism 1984; 27(4):361-8.
3. 3. Groen SS, Sinkeviciute D, Bay-Jensen AC, Thudium CS, Karsdal MA, Thomsen SF, Schett G, Nielsen SH. Exploring IL-17 in spondyloarthritis for development of novel treatments and biomarkers. Autoimmunity Reviews 2021; 20(3):102760.
4. 4. Danve A, O'Dell J. The ongoing quest for biomarkers in Ankylosing Spondylitis. International Journal of Rheumatic Diseases 2015; 18(8):826-34.
5. 5. Calin A, Garrett S, Whitelock H, Kennedy LG, O'Hea J, Mallorie P, Jenkinson T. A new approach to defining functional ability in ankylosing spondylitis: the development of the Bath Ankylosing Spondylitis Functional Index. J rheumatol 1994; 21(12):2281-5.
6. 6. Garrett S, Jenkinson T, Kennedy LG, Whitelock H, Gaisford P, Calin A. A new approach to defining disease status in ankylosing spondylitis: the Bath Ankylosing Spondylitis Disease Activity Index. The Journal of rheumatology 1994; 21(12):2286-91.
7. 7. Aggarwal S, Ghilardi N, Xie M-H, de Sauvage FJ, Gurney AL. Interleukin-23 promotes a distinct CD4 T cell activation state characterized by the production of interleukin-17. Journal of Biological Chemistry 2003; 278(3):1910-4.
8. 8. Oppmann B, Lesley R, Blom B, Timans JC, Xu Y, Hunte B, Vega F, Yu N, Wang J, Singh K, Zonin F, Vaisberg E, Churakova T, Liu M, Gorman D, Wagner J, Zurawski S, Liu Y, Abrams JS, Moore KW, Rennick D, de Waal-Malefyt R, Hannum C, Bazan JF, Kastelein RA. Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12. Immunity 2000; 13(5):715-25.

9. 9. Chen WS, Chang YS, Lin KC, Lai CC, Wang SH, Hsiao KH, Lee HT, Chen MH, Tsai CY, Chou CT. Association of serum interleukin-17 and interleukin-23 levels with disease activity in Chinese patients with ankylosing spondylitis. Journal of the Chinese Medical Association 2012; 75(7):303-8.
10. 10. Wang X, Lin Z, Wei Q, Jiang Y, Gu J. Expression of IL-23 and IL-17 and effect of IL-23 on IL-17 production in ankylosing spondylitis. Rheumatology international 2009; 29:1343-7.
11. 11. Mei Y, Pan F, Gao J, Ge R, Duan Z, Zeng Z, et al. Increased serum IL-17 and IL-23 in the patient with ankylosing spondylitis. Clinical rheumatology 2011; 30:269-73.
12. 12. Shen H, Goodall JC, Hill Gaston J. Frequency and phenotype of peripheral blood Th17 cells in ankylosing spondylitis and rheumatoid arthritis. Arthritis & Rheumatism: Official Journal of the American College of Rheumatology 2009; 60(6):1647-56.
13. 13. Braun J, Sieper J. Ankylosing spondylitis. The Lancet 2007; 369(9570):1379-90.
14. 14. Garg N, Van den Bosch F, Deodhar A. The concept of spondyloarthritis: where are we now? Best practice & research Clinical rheumatology 2014; 28(5):663-72.
15. 15. Van der Heijde D, Ramiro S, Landewé R, Baraliakos X, Van den Bosch F, Sepriano A, Regel A, Ciurea A, Dagfinrud H, Dougados M, van Gaalen F, Géher P, van der Horst-Bruinsma I, Inman RD, Jongkees M, Kiltz U, Kvien TK, Machado PM, Marzo-Ortega H, Molto A, Navarro-Compàn V, Ozgocmen S, Pimentel-Santos FM, Reveille J, Rudwaleit M, Sieper J, Sampaio-Barros P, Wiek D, Braun J. 2016 update of the ASAS-EULAR management recommendations for axial spondyloarthritis. Annals of the rheumatic diseases 2017; 76(6):978-91.
16. 16. Elbey B. Ankilozan spondilitli hastalarda güncel tedavi yaklasimlari/Current treatment approaches in patients with ankylosing spondylitis. Dicle Tip Dergisi 2015; 42(1):123.
17. 17. Aksu K. Ankilozan spondilit tedavisinde sertolizumab pegol. RAED Journal/RAED Dergisi. 2015.