Expression of low-density lipoprotein-related receptors 5 and 6 (LRP5/6) in psoriasis skin.

Low-density lipoprotein-related receptors 5 and 6 (LRP5/6) are transmembrane receptors with key functions in canonical Wnt signalling. Wnt ligands are thought to play an important role in innate immunity and psoriasis, and recent studies assigned LRP5/6 anti-inflammatory properties. The objective of this study was to investigate the expression of LRP5 and LRP6 in lesional and non-lesional skin in peripheral blood and in mononuclear cells of patients with chronic plaque type psoriasis compared with control individuals. To investigate the effect of UV-B radiation, LRP5/6 skin gene expression was analysed before and after narrowband UV-B treatment. Our results showed significantly decreased gene expression of LRP5 and LRP6 in lesional skin and in peripheral blood from patients with psoriasis compared with non-lesional skin and healthy control skin. Immunohistochemistry did not reveal differences in protein expression of LRP5/6. Narrowband UV-B treatment induced a significant increase in LRP5 and LRP6 gene expression in lesional skin. Decreased gene expression of LRP5/6 in lesional skin and upregulation after nb UV-B treatment suggest a possible role for LRP5/6 in psoriasis.

Elevated LRP6 levels correlate with vascular endothelial growth factor in the vitreous of proliferative diabetic retinopathy.

PURPOSE: To measure intravitreal low-density lipoprotein receptor-related protein 6 (LRP6) and vascular endothelial growth factor (VEGF) levels in the eyes of patients with proliferative diabetic retinopathy (PDR) and to observe their correlation with PDR activity. METHODS: Fifty-five eyes of 55 patients were enrolled consecutively. Vitreous samples from 30 eyes with PDR and 25 eyes with nondiabetic macular disease were collected. Active PDR was present in 16 patients and quiescent PDR in 14 patients according to retinal neovascularization. LRP6 and VEGF concentrations in samples were determined using enzyme-linked immunosorbent assay (ELISA). RESULTS: ELISA revealed significant increases in the vitreous levels of VEGF in eyes affected with PDR compared to the controls (p<0.001). The mean concentrations of LRP6 were also higher in the vitreous samples from patients with PDR compared to the nondiabetic controls: 39.85 ng/ml and 15.48 ng/ml, respectively (p=0.002). In addition, the vitreous levels of LRP6 and VEGF were significantly higher in active PDR than in quiescent PDR (p=0.022 and p=0.015, respectively). Furthermore, a significant positive correlation was found between intravitreal levels of LRP6 and VEGF in patients with PDR (r=0.567, p=0.001). However, comparison of patients with PDR with controls revealed that the plasma levels of LRP6 were not significantly different between the two groups (p=0.636). CONCLUSIONS: LRP6 and VEGF levels in the vitreous body from patients with PDR were increased and correlated mutually. LRP6 may be a good diagnostic biomarker and a new therapeutic target for PDR.

Low sclerostin levels: a predictive marker of persistent inflammation in ankylosing spondylitis during anti-tumor necrosis factor therapy?

INTRODUCTION: Sclerostin levels have been reported to be low in ankylosing spondylitis (AS), but there is no data regarding the possible role of this Wnt inhibitor during anti-tumor necrosis factor (TNF) therapy. The present study longitudinally evaluated sclerostin levels, inflammatory markers and bone mineral density (BMD) in AS patients under anti-TNF therapy. METHODS: Thirty active AS patients were assessed at baseline, 6 and 12 months after anti-TNF therapy regarding clinical parameters, inflammatory markers, BMD and baseline radiographic damage (mSASSS). Thirty age- and sex-matched healthy individuals comprised the control group. Patients' sclerostin levels, sclerostin binding low-density lipoprotein receptor-related protein 6 (LRP6) and BMD were evaluated at the same time points and compared to controls. RESULTS: At baseline, AS patients had lower sclerostin levels (60.5 ± 32.7 vs. 96.7 ± 52.9 pmol/L, P = 0.002) and comparable sclerostin binding to LRP6 (P = 0.387) than controls. Improvement of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Metrology Index (BASMI), Ankylosing Spondylitis quality of life (ASQoL) was observed at baseline vs. 6 vs. 12 months (P < 0.01). Concomitantly, a gradual increase in spine BMD (P < 0.001) and a positive correlation between baseline mSASSS and spine BMD was found (r = 0.468, P < 0.01). Inflammatory parameters reduction was observed comparing baseline vs. 6 vs. 12 months (P <0.01). Sclerostin levels progressively increased [baseline (60.5 ± 32.7) vs. 6 months (67.1 ± 31.9) vs. 12 months (72.7 ± 32.3) pmol/L, P <0.001]. At 12 months, the sclerostin levels remained significantly lower in patients compared to controls (72.7 ± 32.3 vs. 96.70 ± 52.85 pmol/L, P = 0.038). Moreover, sclerostin serum levels at 12 months were lower in the 10 patients with high C reactive protein (CRP) (≥ 5 mg/l) compared to the other 20 patients with normal CRP (P = 0.004). Of note, these 10 patients with persistent inflammation also had lower sclerostin serum levels at baseline compared to the other patients (P = 0.023). Univariate logistic regression analysis demonstrated that AS patients with lower sclerostin serum levels had an increased risk to have high CRP at 12 months (odds ratio = 7.43, 95% CI 1.23 to 45.01, P = 0.020) than those with higher sclerostin values. CONCLUSIONS: Persistent low sclerostin levels may underlie continuous inflammation in AS patients under anti-TNF therapy.