AB0193 ROLE OF DICKKOPF-1 IN RHEUMATOID ARTHRITIS

Abstract

Background:Rheumatoid arthritis (RA) is characterized by persistent synovitis that leads to structural joint damage causing deformity and disability. Dickkopf-1(DKK-1) was shown to be a major regulator of joint remodeling, which is associated with subchondral bone erosion in RA. Dickkopf-1 is a secreted glycoprotein that also acts as a potent negative regulator of wingless signaling. Current therapies used to treat RA are not able to effectively repair damaged bone. There is a strong relationship between Wnt signaling pathway, RA and DKK-1 so; this relationship may be a therapeutic point of interestObjectives:To assess the correlation between Dickkopf-1 and RA disease activity, disability, severity and functional status.Methods:Fifty patients fulfilled the 2010 ACR -EULAR criteria for RA were included. Twenty five healthy age and sex matched individuals served as a control (for assessment of serum DKK-1 level). Excluded from the study, patients with Paget disease, Multiple myeloma, Breast cancer, Bone metastasis, Diabetes mellitus, Hyperthyroidism, patients on medication that influence bone metabolism as: heparin, anticonvulsant or thyroxin.All patients were subjected to full history and examination. Disease activity measures as disease activity score (DAS 28-ESR), Visual analogue scale (VAS) and Disease disability indices including ACR criteria of functional status in RA and Health assessment questionnaire disability index (HAQ-DI). Erythrocyte sedimentation rate (ESR), C-Reactive protein (CRP), Rheumatoid factor (RF), Anti citrullinated peptide antibody (ACPA) and Serum dickkopf-1 level. Simple erosion narrowing score (SENS) and Ultrasound DAS (US DAS) were done for all patients. Ultrasound DAS included 28 joints, Power Doppler ultrasound (PDUS) examination of 22 joints and gray scale ultrasound (GSUS) examination for Effusion/Hypertrophy (E/H) of 28 joints. Ultrasound erosion count (USEC) and Ultrasound erosion rate (USER) were assessed.Results:Dickkopf-1 level in RA patients ranged from 66 to 453 ng/ml while in the control group ranged from 15 to 87 ng/ml with statistically significant difference. RA patients were grouped in to: group 1 included 15 (30%) patients with normal DKK-1 level and group 2: included 35 (70%) patients with elevated DKK-1. The differences between both groups were highly significant regarding clinical and laboratory measures (duration of morning stiffness, DAS 28, VAS, ESR, CRP, RF and ACPA), and regarding HAQ-DI, SENS and US DAS. We found significant positive correlation between DKK-1 level and laboratory measures (ESR, CRP, RF, ACPA), radiographic parameters (SENS and erosion score), ultrasonographic parameters (US DAS, USEC and USER) and with HAQ-DI and functional status.Conclusion:Serum level of dickkopf-1 was elevated in RA patients and the results demonstrated the relationship between increased dickkopf-1 level and increased disease activity, decreased functional capacity and chronic structural damage suggesting its important role in the pathogenesis of RA.