1. Serum Dickkopf-1 ( DKK-1) and Arthritis in Systemic Lupus Erythematosus Patients S. I. Nasef, H. H. Omar Samah Ismail Nasef MD, MRCP Rheumatology UK Lecturer of Rheumatology and Rehabilitation Suez Canal University

2. Introduction

3. Introduction SLE is a complex rheumatic disease characterized by multiple organ damages and immunological abnormalities. Among the diverse clinical manifestations, arthritis is one of the most common features. Arthritis in SLE is usually considered as mild and non-erosive However, chronic pain and deformities are frequently reported by patients with longstanding disease.

4. The underlying mechanism for arthritis and joint damage in SLE is still not very clear. It is increasingly recognized that Wingless (Wnt) pathway is considered as a key signalling pathway in bone homeostasis. Introduction

5. It is important for the growth and differentiation of osteoblasts. Dickkopf-1 (Dkk-1) is an inhibitory molecule that regulates the Wnt pathway. Introduction

8. 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. Introduction

9. Aim of the Study

10. To identify the sensitivity, specificity and cut- off value of serum DKK1 in SLE patients with arthritis.

11. Subjects and Methods

12. Methods We recruited 44 SLE patients fulfilling the revised ACR classification criteria (1997) for SLE from the Rheumatology department at Suez Canal University hospital and 40 age and gender-matched healthy control subjects.

13. Patients were divided into 2 groups; The first group included 22 SLE with arthritis The second group included 22 SLE patients without arthritis or joint involvement. Methods

14. Diagnosis of Arthritis was based on the ACR definition in the classification criteria for SLE. Arthritis must have been documented by the treating physician and have been present for at least the two weeks preceding the clinic visit. Methods

15. Patients with SLE and concomitant RA (rhupus) and subjects with osteoarthritis were excluded from the study. We used SLE disease activity index (SLEDAI) for assessment of disease activity. Methods

16. Serum DKK1 was measured using ELISA technique (R&D, Minneapolis, MN, USA). We measured ANA, anti-dsDNA, C3, C4, CRP, ESR, RF and Anti-CCP. Plain X-ray for the hands was done to all patients. Methods

17. Results

18. Results Mean age of the patients was 32.1 years and mean age of the controls was 32.07 years. Females were predominant in the study (88.6% of patients and 87.5% of controls). Mean disease duration was 5.6 years. Mean SLEDAI was 11.7±6.8.

19. SLE Disease Activity

25. Patients with SLE had significantly increased serum DKK1 (2749±1675 pg/ml) compared to controls (2020±771 pg/ml) (P<0.019). By receiver operating characteristics (ROC) analysis, serum DKK1 with a diagnostic cut-off value of 1560 pg/mL can differentiate between SLE patients and healthy individuals with a sensitivity of 82.5%, and a specificity of 45.5%. Results

26. P Value <0.019

27. 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). 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%. Results

28. P Value <0.042

30. Results Serum DKK1 couldn’t differentiate between active and inactive SLE patients. Serum DKK1 didn't show any correlations with markers of inflammation including CRP and ESR. No correlation was found between serum DKK1 and presence of antibodies including ANA and anti-dsDNA.

31. We didn’t find significant correlations between serum DKK1 and C3, C4 or anti- CCP levels. Similarly, no associations were observed between circulating DKK-1 levels and disease duration, age or other system involvements. Results

32. Conclusions

33. 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. Strategies that block DKK1 may be of potential therapeutic interest.

34. Samah Nasef