Plasma transforming growth factor β₁as a biomarker of psoriasis activity and treatment efficacy

Abstract

Transforming growth factor-beta(1) (TGFbeta(1)) is thought to be an inhibitor of the keratinocyte hyperproliferation associated with psoriasis. The aim of this study was to evaluate plasma TGFbeta(1) and TGFbeta(2) concentrations in psoriatic patients as possible indicators of treatment efficacy. TGFbeta concentrations were measured in the plasma of 26 patients with psoriasis using an enzyme immunoassay and analysed with respect to the psoriasis area and severity index (PASI) before and after treatment with salicylic acid and/or sulphur followed by dithranol ointment. Baseline plasma concentrations of both TGFbeta(1) and TGFbeta(2) (20.3+/-2.2 ng ml(-1) and 0.14+/-0.02 ng ml(-1), respectively) did not differ significantly from control values (18.3+/-1.6 ng ml(-1) and 0.14+/-0.03 ng ml(-1), respectively). However, a significant positive correlation (r=0.69) between the baseline PASI and TGFbeta(1), but not TGFbeta(2), values was demonstrated. The pretreatment TGFbeta(1) concentration in patients with a PASI >/=15 (26.6+/-3.2 ng ml(-1)) was significantly higher than control values. There were no significant elevation of pretreatment TGFbeta(1) concentrations in patients with a PASI<15, or with respect to TGFbeta(2) in both groups. Treatment caused a significant decrease in TGFbeta(1), but only in patients with a PASI>/=15. Patients with baseline TGFbeta(1) concentrations exceeding the mean of the control group had a PASI value that was significantly higher than that of patients with a TGFbeta(1) concentration below the mean of the controls. These results confirmed an association between plasma TGFbeta(1) concentration and psoriasis severity, and demonstrated its normalization during treatment. Measurement of TGFbeta(1) in plasma should be considered as a possible biomarker of psoriasis activity during its management.

Plasma TGF-β1, TIMP-1, MMP-1 and IL-18 as a combined biomarker of psoriasis activity

“…Psoriatic patients (Flisiak et al 2002(Flisiak et al , 2003. A possible reason for the elevated TGF-b 1 plasma level could be skin inflammation associated with disease activity, which was supported by a significant correlation between TGF-b 1 concentration in psoriatic scales and sedimentation rate as we previously demonstrated (Flisiak et al 2002).…”

“…A possible reason for the elevated TGF-b 1 plasma level could be skin inflammation associated with disease activity, which was supported by a significant correlation between TGF-b 1 concentration in psoriatic scales and sedimentation rate as we previously demonstrated (Flisiak et al 2002). Another source could be the vascular expansion associated with activation of endothelial cells and fibroblasts which are known as important source of TGF-b 1 (Singer & Clark 1999, Oyama et al 2000, Flisiak et al 2003. The possible Plasma TGF-b 1 , TIMP-1, MMP-1 and IL-18 as combined biomarker for psoriasis 553 role of TGF-b 1 in the pathogenesis of psoriasis is related to inhibition of T-lymphocyte adhesiveness to dermal microvascular endothelial cells, so reduction of its expression and function may contribute to lymphocyte infiltration into psoriatic plaques (Cai et al 1996).…”

Downregulation of SMAD2, 4 and 6 mRNA and TGFβ Receptor I mRNA in Lesional and Non-lesional Psoriatic Skin

“…Mutations in the TGFß genes, its receptors, and intracellular signalling molecules (SMAD proteins) are associated with thepathogenesisofcancer(l3). Despite this important influence ofTGFß on the homeostasis of human tissue there have been only a few studies into the role ofTGFß and its intracellular signalling proteins (SMAD) in the pathogenesis of psoriasis (14)(15)(16)(17). As psoriasis is characterized by epidermal hyperproliferation, and several studies showed anti-proliferative effects ofTGFß on keratinocytes (6,18,19), we investigated the mRNA expression ofTGFß, its receptors and signalling molecules (SMADs) in psoriatic skin.…”

A Role for TGFβ Signaling in the Pathogenesis of Psoriasis

“…In contrast, TGFβ1 is barely detectable in normal skin epidermis because of its short half-life time(Wakefield et al, 1990;Wataya-Kaneda et al, 1994;Quan et al , 2002;Han et al , 2005). Successful treatment resulted in reduced serum levels of TGFβ1 in patients with psoriasis (Flisiak et al, 2003). The mechanism for increased serum levels of TGFβ1 in patients with psoriasis remains unclear.…”