Serum and synovial fluid levels of p40 IL12/23 in spondyloarthropathy patients

Abstract

IL-23 is the main inductor in Th17 polarization of naive T cells, inducing IL-17 production. IL-17 has been demonstrated to be elevated in ankylosing spondylitis (AS). The p40 subunit is common to IL-12 and IL-23. We assessed serum and synovial levels of p40 IL12/23 in spondyloarthropathy (SpA) patients and the evolution under anti-TNF. SpA patients fulfilling ESSG criteria were included. Healthy volunteers served as controls. P40 IL12/23 was assessed using Human Quantikine ELISA (R&D Systems), and at the same time, BASDAI, ESR, CRP, IL-17, MMP-3. Patients treated with anti-TNF were evaluated again after 10 weeks of treatment. Statistical analysis used Mann Whitney and correlation tests. Twenty-seven SpA outpatients (20 men), mean age 40.3 years, mean disease duration 10.5 years, HLA B27 positive n = 21, peripheral arthritis n = 8, mean BASDAI 45.7, mean CRP 30.7 mg/l, and 24 controls (12 men), mean age 50.4 years, were included. There is no statistical difference in serum levels of p40IL12/23 between patients (mean 77.8 pg/ml) and controls (103 pg/ml) and between patients with axial and peripheral involvement. Levels were higher in HLA B-27 negative patients (p = 0.02). No statistical correlation was found between p40 IL12/40 serum levels and each of BASDAI, ESR, CRP, serum levels of IL 17, MMP 3. Fourteen AS patients were treated with TNF blockers. Whereas significant reduction in BASDAI, ESR, and CRP were obvious after treatment, there was no significant change in serum level of p40 IL12/23. Mean levels of synovial p40 IL12/23 were higher in SpA patients (n = 6; mean 536 pg/ml) compared to osteoarthritis patients (n = 3; 133 pg/ml) and compared with paired serum SpA levels. These results suggest that serum levels of p40 IL-12/23 may not be considered as a biologic tool of disease activity assessment in SpA patients.

Evaluation of the T helper 17 axis in ankylosing spondylitis

“…There are a limited number of studies on IL-23 levels in AS. A recent study found increased IL-23 in AS [10], but other studies reported contradicting results [8,11]. In this study, the concentrations of both IL-12 and IL-23 were significantly higher in AS patients; we also found AS patients had significantly higher TGF-b and IL-6 concentrations, which are responsible for the differentiation of Th-17 cells [18].…”

“…Recent studies suggest interleukin-23 receptor (IL-23R) is one of the major generic factors involved in one's susceptibility to AS [1][2][3][4]. In accordance with this observation, recent studies focused on the T helper 17 (Th17) axis in patients with AS or spondyloarthropathy (SpA) [5][6][7][8][9][10][11]. However, the available data is still limited and additional information is needed.…”

IL12/IL23 Inhibition in the Treatment of Psoriatic Arthritis

“…Later studies showed that patients with SpA have elevated IL12 and IL23 levels in their synovial fluid and peripheral blood [21]. Elevated IL23 levels have been linked to the presence of human leukocyte antigen B27 (HLA-B27) positivity among these patients [22].…”

IL-23 and IL-17 in ankylosing spondylitis

“…Previous studies did not demonstrate elevated levels of p40 IL-23 in the serum of AS patients, compared with controls, whereas, in some of them, synovial fluid levels were higher than serum levels [7]. This gives the central role to p40 IL-23 in the pathophysiological axis, and a potential theraputic target in AS.…”