Abstract
Semaphorin 3A (Sema3A) and semaphorin 4D (Sema4D) are molecules which regulate immune responses as well as bone remodeling process. The aim of this study was to evaluate the serum levels of Sema3A and Sema4D and to investigate their clinical significance in rheumatoid arthritis (RA). The serum levels of Sema3A and Sema4D were measured in 130 patients with RA and 65 sex- and age-matched healthy individuals. Circulating levels of biomarkers of RA-related inflammation and bone turnover such as tumor necrosis factor- (TNF-) α, interleukin- (IL-) 6, IL-22, IL-34, osteopontin, Dkk-1, and sclerostin were also measured. Disease activity was determined by the 28-joint disease activity score (DAS28), and radiographic joint damage was assessed by the modified Sharp van der Heijde score (SHS). The serum levels of Sema3A were significantly higher in patients with RA than those in healthy controls (p < 0.001), whereas serum4D levels did not differ between the two groups. The levels of Sema4D showed a positive correlation with C-reactive protein (p = 0.001) and IL-6 (p < 0.001) levels, whereas the levels of Sema3A showed a negative correlation with Dkk-1 (p = 0.007) and TNF-α (p = 0.001). Even though Sema3A and Sema4D levels were comparable between RA patients with DAS28> 3.2 and with DAS28 ≤ 3.2, RA patients with radiographic progression (ΔSHS change/year ≥ 1) had significantly higher baseline levels of Sema4D than those without progression (p = 0.029). Additionally, when RA patients were divided into 3 groups using tertiles of Sema4D levels, the percentage of progressors was significantly increased (p = 0.045). In multivariate logistic regression analysis, serum Sema4D levels were an independent risk factor for radiographic progression. Our results suggest that the baseline levels of Sema4D might be a useful marker to identify RA patients with subsequent radiographic progression and that Sema4D may be an active mediator involved in RA-induced joint damage.
Highlights
Rheumatoid arthritis (RA) is a chronic systemic inflammatory arthritis characterized by synovitis of peripheral joints, which potentially results in irreversible joint destruction and disability
Semaphorin 3A (Sema3A) Levels Were Significantly Elevated in Patients with RA, but Not semaphorin 4D (Sema4D)
We found that the serum levels of Sema3A were elevated in RA patients but were not related to radiographic progression
Summary
Rheumatoid arthritis (RA) is a chronic systemic inflammatory arthritis characterized by synovitis of peripheral joints, which potentially results in irreversible joint destruction and disability. The early diagnosis and intensive treatment of RA and the development of biologic disease-modifying antirheumatic drugs (DMARDs) have improved treatment outcomes [2,3,4], radiographic damage still occurs in a Disease Markers considerable number of RA patients. 20% of very early RA patients show erosive joint damage within 2 years, and progressive joint damage is observed even in some RA patients with clinical remission as well as drug-free remission [5, 6]. Because the progression of joint damage is closely linked to disability in RA [7], a number of studies have attempted to identify prognostic markers for radiographic progression. Several candidate biomarkers, including inflammatory proteins, cytokines, chemokines, and matrix-degrading enzymes, have been suggested in previous studies [8]
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