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FRI0513 Decreased Skin Expression but Normal Circulating Levels and Function of Dickkopf-1 in Patients with Systemic Sclerosis
  1. D. Daoussis1,
  2. I. Antonopoulos1,
  3. A. Tsamandas2,
  4. A.P. Andonopoulos1
  1. 1Rheumatology
  2. 2Department of Pathology, University of Patras Medical School, Patra, Greece

Abstract

Background The critical question of what drives fibroblast activation in systemic sclerosis (SSc) remains unanswered. The Wnt pathway, a known regulator of osteoblastogenesis, has also emerged as a crucial mediator of the fibrotic process. It was recently reported that Dickkopf-1 (Dkk-1), an inhibitor of the Wnt pathway, is absent from scleroderma skin1. No data exist on circulating levels and function of Dkk-1 in patients with SSc.

Objectives To assess: i) circulating levels and function of Dkk-1 in patients with SSc and ii) skin expression of Dkk-1 in SSc and investigate potential correlations with clinical and demographic characteristics.

Methods Circulating Dkk-1 levels were measured in 50 patients with SSc and 50 healthy subjects, age and sex matched, using an established solid phase immunoassay. The functional integrity of Dkk-1 was assessed by a functional ELISA which measures only Dkk-1 bound to LRP6 receptor. Skin biopsies were obtained from 12 patients with SSc and 5 healthy subjects and Dkk-1 skin expression was assessed by immunohistochemistry

Results Patients were predominantly female (84%) with a mean age (±SEM) of 57.3 (±2.1) years. Most had diffuse disease (64%) with a mean MRSS (±SEM) of 17.1 (±1.2) and a mean (±SEM) disease duration of 8 (±1.3) years. Circulating levels of Dkk-1 did not differ significantly in patients with SSc compared to healthy subjects (mean ±SEM: 1603±154 pg/ml vs 1889±95 pg/ml for patients with SSc and healthy subjects, respectively, p=0.1). We found no correlation of circulating Dkk-1 levels with age, gender, disease duration, disease type, MRSS, HAQ-DI, inflammatory markers and PFT's. Patients with SSc had similar functional Dkk-1 levels compared to healthy subjects (mean ± SEM: 257.8±89.5 pg/ml vs 325±74.9 pg/ml for patients with SSc and healthy subjects, respectively, p=ns). In all skin biopsies obtained from healthy subjects, Dkk-1 was expressed at the epidermis, appendices and spindle like cells in the dermis. In sharp contrast, no Dkk-1 expression could be detected in spindle-like cells in the dermis in all patients with SSc; only 2 patients exhibited a weak expression at the epidermis.

Conclusions Circulating levels and function of Dkk-1 are not impaired in patients with SSc despite the striking lack of skin expression. These data indicate that local factors suppress Dkk-1 expression in scleroderma skin

References

  1. Akhmetshina et al. Nat Commun 2012.

Disclosure of Interest None declared

DOI 10.1136/annrheumdis-2014-eular.4078

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