Background Systemic lupus erythematosus (SLE) is a chronic multi-organ autoimmune disease. Among the various clinical manifestations, arthritis is one of the most common features. Arthritis in SLE is usually considered mild and non-erosive; however, chronic pain and deformities are frequently reported by patients with longstanding disease. The underlying mechanism for arthritis and joint damage in SLE is not very clear. It is increasingly recognized that Wnt pathway is considered as a key signalling pathway in bone homeostasis. Dickkopf-1 (DKK-1) is an inhibitory molecule that regulates the Wnt pathway. The potential role of DKK1 in the pathogenesis of arthritis in SLE patients is not clearly understood. Therefore, we are investigating the relationship between serum DKK-1 and arthritis in patients with SLE aiming at finding new therapeutic targets in SLE patients.
Objectives To identify the sensitivity, specificity and cut-off value of serum DKK1 in SLE patients with arthritis.
Methods We recruited 84 subjects (44 SLE patients and 40 age and gender-matched healthy control subjects). SLE patients were divided into 2 groups; the first group included 22 SLE with arthritis and the second group included 22 SLE patients without arthritis or joint involvement. Arthritis was based on the American college of rheumatology (ACR) definition in the classification criteria for SLE.To be included in the analyses, the arthritis must have been documented by the treating physician and have been present for at least the two weeks preceding the clinic visit. We used SLE disease activity index (SLEDAI) for assessment of disease activity. Active lupus was defined as SLEDAI ≥4. Serum DKK1 was measured using ELISA. We measured anti-dsDNA, C3, C4, CRP and ESR. Plain X-ray was done to all patients.
Results Mean age of the patients was 34.6±4.7 and mean age of the controls was 32.07±8.1. Most of the study groups were females (88.6% of the patients and 87.5% of the controls). Mean disease duration was 8.4±4.5 years. Mean SLEDAI was 10.7±6.8.
Patients with SLE had significantly increased serum DKK1 (2749±1675 pg/ml) compared to controls (2020±771 pg/ml) (P<0.019). SLE patients with arthritis had significantly higher levels of serum DKK1 than SLE patients without arthritis (2748±199 pg/ml and 2462±331 pg/ml respectively) (P<0.042).
Serum DKK1 didn't show any correlations with SLEDAI, CRP, ESR, C3, C4 or anti-dsDNA levels. No correlation was found between serum DKK1 and disease duration or age of the patients.
By receiver operating characteristics (ROC) analysis, serum DKK1 could be used to diagnose SLE patients with a diagnostic cut-off value of 1560 pg/mL [area under curve (AUC) 0.631 (95% CI, 0.509- 0.755)], sensitivity 82.5%, and specificity 45.5%. A value of serum DKK1 1920 pg/mL as a cut-off value is best in differentiating SLE patients with arthritis from SLE patients without arthritis with sensitivity 70%, and specificity 50% [(AUC) 0.622 (95% CI, 0.432- 0.813)]. Serum DKK1 couldn't differentiate between active and inactive SLE patients.
Conclusions High serum DKK1 level is associated with arthritis in SLE patients. Therefore, DKK1 could have a role in the pathogenesis of arthritis in SLE patients and strategies that block DKK1 may be of potential therapeutic interest.
Disclosure of Interest None declared