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


Atas N., Cakir B., BAKIR F., UÇAR M., SATIŞ H., Guz G. T., ...More

CLINICAL RHEUMATOLOGY, vol.41, no.5, pp.1381-1389, 2022 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 41 Issue: 5
  • Publication Date: 2022
  • Doi Number: 10.1007/s10067-022-06070-w
  • Journal Name: CLINICAL RHEUMATOLOGY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, CAB Abstracts, EMBASE, MEDLINE, Veterinary Science Database
  • Page Numbers: pp.1381-1389
  • Keywords: 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
  • Gazi University Affiliated: Yes

Abstract

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 naive 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-alpha 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-alpha 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.