ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 529

Ankylosing Spondylitis and Dysfunctional Dkk

Rajbir Gulati1, Maripat Corr2, Michael H. Weisman3 and David Hallegua4, 1Rheumatology, Cedars Sinai Medical Center, Los Angeles, CA, 2Medicine, Univ of California-San Diego, La Jolla, CA, 3Rheumatology, Cedars-Sinai Medical Center, Los Angeles, CA, 4Medicine, Cedars-Sinai/UCLA, Beverly Hills, CA

Meeting: 2013 ACR/ARHP Annual Meeting

Keywords: ,

Session Information

Title: Spondyloarthropathies and Psoriatic Arthritis: Pathogenesis, Etiology, Animal Models I

Session Type: Abstract Submissions (ACR)

Background/Purpose:

Ankylosing Spondylitis (AS) is characterized by inflammation of the spine and entheses followed by formation of syndesmophytes.

Wnt pathway is a regulator of bone and cartilage remodeling; modulated by several biomarkers like Dickkopf (DKK-types 1, 2, 3 & 4), sclerostin, etc.

DKK1 is an inhibitor of Wnt. TNF-alpha inhibits bone formation by inducing Dkk-1.

 AS patients display either low levels of functional DKK1 (DKK1 that binds to LRP5/6- Low-density lipoprotein receptor related protein) or high levels of total DKK1 indicating that it is dysfunctional.

Maksymowych et al, showed that new syndesmophytes developed more frequently in vertebral corners with inflammation on baseline MRI; and more so where inflammation had resolved after 2 years of anti-TNF therapy.

We examined the relationship between inflammation, bone formation and bone biomarkers in AS patients not on anti-TNF therapy. The anthrax toxin binding protein (CMG2) is a decoy receptor for DKK; which has been found to be associated with AS; we examined its association with DKK.

Methods:

We recruited 35 patients with spondyloarthritis, (34 fulfilling New York criteria & 1 fulfilling ASAS criteria for axial spondyloarthritis) from a preexisting cohort, Prospective Study on Ankylosing spondylitis Severity (PSOAS) and from the office of the principal investigator.

During the study visit, metrology measurements were done and BASMI calculated. Bath AS Disease Activity and Functional Indices (BASDAI, BASFI) were also obtained. Blood samples were examined for the following: ESR, CRP, Vitamin D, PTH, DKK, LRPDKK, OPG (Osteoprotegrin), sclerostin, antiDKK, SFRP 3, CMG2DKK, and CMG2LRP. X-rays of the pelvis and the entire spine that were available for 35 and 28 patients respectively were scored for the sacroilitis grade (SI grade) and the modified Stokes Ankylosing Spondylitis Spine Score (mSASSS). Statistical analysis was performed using Spearman correlation coefficient and Student t-test.

Results:

1.      Significant correlation between DKK, LRPDKK& CMGDKK as well as between mSASSS, SI grade and BASMI. (Table 1).

2.      LRPDKK increases with inflammation in AS. Bone formation as indicated by mSASSS trended higher in patients with higher levels of inflammation.

3.      Patients with low CRP when separated based on high or low mSASSS, showed that high mSASSS correlated negatively with DKK and LRPDKK.

                                                             Table 1

Variable

N

Mean

Std. Dev

Median

Minimum

Maximum

Correlation

P-value

Markers of inflammation and function

CRP

32

1.99      

4.64      

0.57

0.03

22.9

ESR         0.83

BASDAI 0.43         

<.0001

0.0119              

ESR

33

23.42     

23.42     

14.00      

1.00

98.00

 

 

BASDAI

34

4.10      

4.49      

3.08            

0.00

24.9

BASFI     0.55    

0.0008

BASFI

34

23.70  

25.52     

14.95            

0.00

99.00

 

 

Bone biomarkers associated with bone formation

DKK

35

4.03

2.93

3.47

0.39

15.52

LRPDKK     0.87

CMG2DKK 0.51

<.0001      

0.0035

LRPDKK

30

2.92

1.52

2.91

0.22

6.39

CMG2DKK 0.55

0.0015

CMG2DKK

30

0.70

0.57

0.39

0.39

2.15

 

 

Radiologic and Mobility measurements

mSASSS

28

18.54  

22.47   

6.5

0.00

72.00

SIJ              0.75         

BASMI      0.80         

<0.0001

<0.0001

SIJ Grade

34

3.29

1.00

4.00

0.00

4.00

BASMI      0.52

0.009

BASMI

25

3.75     

1.64    

4.00

0.6

6.8

 

 

Low versus High CRP groups

LRPDKK(low CRP)

15

–

–

1.98

0.23

4.9

–

0.0009

LRPDKK(high CRP)

12

–

–

4.04

1.38

6.39

–

mSASSS(low CRP)

16

–

–

5.5

0

62

–

0.082

mSASSS(high CRP)

11

–

–

24

0

72

–

DKK and LRPDKK levels influencing mSASSS in low CRP group

DKK(low CRP,low mSASSS)

12

–

–

3.36

2

7.41

–

0.013

DKK(Low CRP, high mSASSS)

4

–

–

0.78

0.39

3.09

–

LRPDKK(low CRP, low mSASSS)

10

–

–

2.32

1.56

4.91

–

0.008

LRPDkk(low CRP,high mSASSS)

4

–

–

1.01

0.23

1.85

–

Conclusion:

Our pilot study suggests that inflammation and low levels of functional DKK are associated with increased bone formation in anti-TNF naïve AS patients. Functional DKK levels increases with active inflammation. However, with low levels of inflammation, functional DKK correlated negatively with AS x-ray changes.  A positive correlation exists between the binding of  LRPDKK to a decoy receptor CMG2 and LRPDKK levels in these patients.

Funded by a grant from the Spondylitis Association of America

 

Disclosure:

R. Gulati,
None;

M. Corr,
None;

M. H. Weisman,
None;

D. Hallegua,
None.

« Back to 2013 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/ankylosing-spondylitis-and-dysfunctional-dkk/