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
Introduction
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.
Introduction
• 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
• It is important for the growth and differentiation of
osteoblasts.
• Dickkopf-1 (Dkk-1) is an inhibitory molecule that
regulates the Wnt pathway.
Introduction
• 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.
Aim of the Study
To identify the sensitivity, specificity and cutoff value of serum DKK1 in SLE patients with
arthritis.
Subjects and Methods
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.
Methods
• 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
• 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
• 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
• 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.
Results
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.
SLE Disease Activity
SLEDAI
50%
45%
37.50%
32.50%
40%
35%
30%
25%
20%
20%
10%
15%
10%
5%
0%
mild
moderate
high
very high
Age (years)
32.6
34
31.6
32
30
SLE with arthritis
SLE without arthritis
Disease duration (years)
6
5.7
5.3
5.5
5
SLE with arthritis
SLE without arthritis
13
14
12
10
10
8
6
4
2
0
SLEDAI with Arthritis
SLEDAI without Arthritis
80
70
65.4 66.7
65.4
SLE with arthritis
60
SLE without arthritis
50
40
30
25.2
25.2
25.2
17
20
10
7
0
CRP, mg/dl
ESR, mm/h
C3, mg/dl
C4, mg/dl
50.00%
45.00%
45.50%
Positive Anti-CCP
Positive anti-dsDNA
40.00%
35.00%
31.80%
30.00%
25.00%
20.00%
15.00%
13.60%
9.10%
10.00%
5.00%
0.00%
SLE with arthritis
SLE without arthritis
Results
• 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%.
DKK1, pg/ml
3000
2749
P Value <0.019
2500
2020
2000
1500
1000
500
0
SLE Patients
Control Subjects
Results
• 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%.
DKK1, pg/ml
P Value <0.042
2,784
2,800
2,750
2,700
2,650
2,600
2,550
2,470
2,500
2,450
2,400
2,350
2,300
SLE without Artrhritis
SLE with Arthritis
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.
Results
• 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.
Conclusions
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.