ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 1797

Wnt Signaling Pathway Status, Determined by Serum Dkk-1 and R-Spondin 1 Levels, in Rheumatoid Arthritis and Ankylosing Spondylitis

Byoong Yong Choi1, Hyon Joung Cho1, Eun Ha Kang2, Yeong Wook Song3 and Yun Jong Lee1, 1Internal Medicine, Seoul National University Bundang Hospital, Seongnam-si, South Korea, 2Internal Medicine, Rheumatology, Seoul National University Bundang Hospital, Seongnam-si, South Korea, 3Division of Rheumatology, Department of Internal Medicine, Seoul National University, Seoul, South Korea

Meeting: 2012 ACR/ARHP Annual Meeting

Keywords:

Session Information

Title: Cytokines, Mediators, and Gene Regulation

Session Type: Abstract Submissions (ACR)

Background/Purpose:

Dickkopf-1 (Dkk-1), known as inhibitor of Wnt signaling pathway, is involved in joint damage in inflammatory arthritis. While R-spondin 1 (Rspo1) reported to protect against bone destruction through antagonizing Dkk-1 in murine arthritis model, the Rspo1 levels in inflammatory arthropathy such as rheumatoid arthritis (RA) and ankylosing spondylitis (AS) has not been investigated. We determined the circulating levels of Rspo1 and Dkk-1 in patients with RA or AS and investigated their clinical implication.

Methods:

Serum sample were collected from 60 RA patients (mean age±SEM 53.3± 1.55, 54 females), 55 AS patients (36.7± 1.61, 8 females), and age-and gender-matched 65 healthy subjects (44.7±1.80, 35 females). Sera from 13 RA patients treated with anti-TNF-α agents were also collected at baseline and 12 weeks. Clinical and laboratory data included age, gender, body mass index, disease duration, medication history, ESR and CRP. Disease activities in RA and AS were measured by DAS28 or BASDAI respectively. Radiographic joint damages in RA were assessed by the modified Sharp/Van der Heijde score (Sharp score). Serum Rspo1 and Dkk-1 levels were determined by sandwich ELISA.

Results:

Serum Rspo1 levels were significantly decreased in RA patients when compared to those in healthy subjects (p<0.0001). However, their levels were comparable between AS patients and healthy subjects. While serum Dkk-1 levels in AS patients were significantly lower than those in healthy subjects (p=0.001), those in RA were significantly higher (p<0.0001). Thus, the ratios of Dkk-1/Rspo1 were significantly elevated in RA patients but significantly suppressed in AS patients (both p<0.0001). Dkk-1/Rspo1 ratios in RA patients with high disease activities (DAS28 > 5.1) were much higher than those in RA patients with low disease activities (DAS28 < 2.6, p=0.012). However, Dkk-1/Rspo1 ratios were not correlated with Sharp scores in RA patients and not different between AS patients with and without syndesmophyte. Serum DKK-1 levels wre not changed but Dkk-1/Rspo 1 ratios were decreased by anti-TNF-α treatment (p=0.0134). Glucocorticoid treatment (p=0.003) or presence of osteoporosis (p=0.044) was associated with increased Dkk-1/Rspo-1 ratios.

Conclusion:

This study demonstrated inappropriate suppression of Wnt signaling pathway, presented by high Dkk-1/Rspo1 ratios, in RA and activation of Wnt signaling pathway in AS. However, the ratios of Dkk-1/Rspo1 levels were not directly associated with the cumulative radiographic change in RA patients although their levels were affected by RA disease activity.

Disclosure:

B. Y. Choi,
None;

H. J. Cho,
None;

E. H. Kang,
None;

Y. W. Song,
None;

Y. J. Lee,
None.

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