The impact of anti-TNF treatment on Wnt signaling, noggin, and cytokine levels in axial spondyloarthritis


Atas N., Çakır B., BAKIR F., UÇAR M., Satış H., Güz G. T., ...Daha Fazla

Clinical Rheumatology, cilt.41, sa.5, ss.1381-1389, 2022 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 41 Sayı: 5
  • Basım Tarihi: 2022
  • Doi Numarası: 10.1007/s10067-022-06070-w
  • Dergi Adı: Clinical Rheumatology
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, CAB Abstracts, EMBASE, MEDLINE, Veterinary Science Database
  • Sayfa Sayıları: ss.1381-1389
  • Anahtar Kelimeler: Anti-TNF treatment, Axial spondyloarthritis, IL-17, Noggin, Wnt signaling, BONE MORPHOGENETIC PROTEIN-2, ANKYLOSING-SPONDYLITIS, RADIOGRAPHIC PROGRESSION, SERUM-LEVELS, STEM-CELLS, IN-VITRO, DIFFERENTIATION, EXPRESSION, MULTICENTER, DICKKOPF-1
  • Lokman Hekim Üniversitesi Adresli: Evet

Özet

© 2022, International League of Associations for Rheumatology (ILAR).Introduction: Anti-tumor necrosis factor (anti-TNF) agents are commonly used in treatment of axial spondyloarthritis (axSpA), but clinical and radiological improvement is not achieved in all patients. We aimed to investigate the impact of anti-TNFs on inflammatory and noninflammatory parameters in patients with axSpA. Methods: In this longitudinal study, 30 biologic naïve axSpA patients with high disease activity and 30 healthy controls were enrolled. All patients were treated with anti-TNF agents for 6 months. ASDAS-CRP, BASDAI, BASFI, BASMI, patient and physician global assessments were evaluated. C-reactive protein, COX2, TNF-α IL-6, IL-17, IL-22, IL-23, IL-33, sclerostin, dickkopf-1, and noggin levels were evaluated at baseline and at 6 months of anti-TNF treatment. Results: At baseline, axSpA patients had significantly higher median (IQR) TNF-α levels, 34.4 (31.4–37.03) vs. 18.1 (12.1–28.4) pg/ml (p < 0.001), and lower DKK1, 446.7 (356.9–529.3) vs. 1088.7 (951.7–1244.4) pg/ml, and sclerostin, 312.4 (140.8–412.7) vs. 412.3 (295.4–512.8) pg/ml, compared to healthy controls (all p < 0.001). The median (IQR) serum levels of IL-17, IL-22, and IL-33 increased significantly after 6 months of anti-TNF treatment, from 93.3 (85.1–104.8) to 102.1 (86.6–114.6) pg/ml (p = 0.026), 159.2 (151.9–178.4) to 183.5 (156.3–304.6) pg/ml (p = 0.033), and 127.8 (106.6–186.1) to 147.06 (128.5–213.4) pg/ml (p = 0.016), respectively. Sclerostin and DKK-1 levels increased significantly after anti-TNF treatment from 312.4 (140.8–412.7) to 405.1 (276.3–452.5) pg/ml (p = 0.018) and 446.7 (356.9–529.3) to 881.3 (663.1–972.2) pg/ml (p < 0.001), while there was no significant change in noggin level. Conclusions: Many inflammatory cytokines increase after anti-TNF treatment and noggin is not affected by anti-TNF treatment in AxSpA. Noggin might be a therapeutic target in patients with axSpA. Key Points: • Anti-TNF therapy is not sufficient for complete blockage of the inflammatory process in axial spondyloarthritis. • The increase in IL-17, IL-22, and IL-33 may decrease the efficiency of anti-TNF therapy. • Noggin might be a therapeutic target as a complementary or alternative approach to anti-TNF therapy in axial spondyloarthritis.