AB0118 Evaluation of wingless (wnt) pathway inhibitors dickkopf-1 and sclerostin and il-23-th17-il-17 pathway in patients with ankylosing spondylitis and non-radiographic axial spondyloarthritis

Autor: Cagri Sakalar, Ö. Akgü, S. Ozgocmen
Rok vydání: 2013
Předmět:
Zdroj: Annals of the Rheumatic Diseases. 72:A821.3-A821
ISSN: 1468-2060
0003-4967
DOI: 10.1136/annrheumdis-2013-eular.2441
Popis: Background Inflammation and new bone formation is characteristic in spondyloarthritis (SpA). Wingless (Wnt) pathway is one of the regulator elements of bone formation and inhibited by Dickkopf-1 (Dkk-1) and sclerostin which results retardation of bone formation. Current data reveal that new bone formation continues despite potent inhibition of inflammation by anti-tumor necrosis factor-α (anti-TNF-α) suggesting that inflammation and new bone formation may have distinct pathways and mechanisms. Biopsies of the sacroiliac joints showed that inflammation in SpA at least partly mediated with TNF-α however about 30% of the patients treated with anti-TNF-α have still active disease suggesting that some other pathways such as interleukin (IL)-23-Th17-IL-17 pathway and cytokines may also induce tissue inflammation and autoimmunity. Objectives To evaluate the serum Dkk-1 and sclerostin levels and IL-23-Th17-IL-17 pathway in patients with established ankylosing spondylitis (AS) and patients with non-radiographic axial spondyloarthritis (nr-axSpA) and their relation with disease activity and radiographic damage. Methods Patients who met mNY criteria for AS or ASAS criteria for axial SpA were consecutively recruited. Sacroiliac and lumbar spinal MR images were taken in all patients. Age and sex matched healthy subjects were recruited as controls. Patients who met ASAS criteria but had no definite sacroiliitis on pelvic X-rays were defined as nr-axSpA. Serum Dkk-1, sclerostin, IL-23, IL-17, IL-6, TNF-α, ESR, CRP, complete blood count were assessed in patients and healthy controls. BASDAI, BASMI were calculated. Radiographs were scored according to modified Stoke AS Spine Score (mSASSS) by an experienced rheumatologist who was blind to the patients identity. Analysis of variances with Tukey’s test was used for the comparisons between groups. Results Twenty-eight patients with nr-axSpA, 29 patients with AS and 25 healthy control were included. Dkk-1 levels were relatively higher in patients with AS 1353.61 pg/ml (95% CI: 1085.15-1622.07) and nr-axSpA 1136.64 pg/ml (95% CI: 887.28-1385.99) however only statistically significant in AS vs healthy controls, 860.72 pg/ml (95% CI: 711.66-1009.79), p=0.009. Sclerostin levels were similar in patients with AS 308.47 pg/ml (95% CI: 195.80-421.05) and nr-axSpA 281.70 pg/ml (95% CI: 233.94-329.46) and healthy controls 217.14 pg/ml (95% CI: 183.06-251.22). There was no correlation between Dkk-1 or sclerostin levels with BASDAI, acute phase reactants, BASMI and mSASSS in both patient groups. Serum IL-23 levels were relatively higher in patients with AS 3.12 pg/ml (95% CI: 2.26-3.98) and nr-axSpA 2.36 pg/ml (95% CI:1.83-2.89) however only statistically significant in AS vs healthy control 1.90 pg/ml (95% CI: 1.14-2.66). Interleukin-17 levels were similar in patients with AS 203.36 pg/ml (95% CI: 130.99-275.72) and nr-axSpA 195.45 pg/ml (95% CI: 159.36-221.54) and healthy controls 137.89 pg/ml (95% CI: 86.10-189.68). Also IL-6 and TNF-a levels were similar between patient groups and controls. Conclusions This study showed that serum Dkk-1 and IL-23 levels increased in patients with established AS. Conflicting results in the literature on DKK-1 levels as well as our results support the notion that inflammation and bone formation may have distinct pathways and mechanisms. Disclosure of Interest None Declared
Databáze: OpenAIRE
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