Circulating peroxisome proliferator-activated receptor γ is elevated in systemic sclerosis

Abstract

Introduction: Systemic sclerosis (SSc) is an autoimmune connective tissue disease with distinguished fibrosis of the skin and internal organs. Vascular damage, immune dysregulation and fibroblasts activation contribute to SSc pathogenesis. Peroxisome proliferator-activated receptor γ (PPAR-γ) can be a link between cell metabolism and fibrosis in SSc due to its anti-fibrotic and immunomodulatory properties.

Aim: To measure the serum level of PPAR-γ in SSc patients and correlate it with the SSc subtype, hs-CRP, disease duration, vascular and internal organ involvement.

Material and methods: Twenty-two SSc patients (15 limited SSc, 7 diffuse SSc) matched with healthy controls were analysed. Clinical and laboratory data were collected including specific antibodies, interstitial lung disease, oesophageal involvement, digital pitting scars, disease duration, Raynaud's phenomenon (RP) and modified Rodnan skin score (mRSS). PPAR-γ levels were analysed by ELISA. Statistical analysis was performed with χ², Student's t-test and Mann-Whitney-U test. Pearson and Spearman correlation analyses were used to establish variables association. The significance threshold was set at p < 0.05.

Results: PPAR-γ concentration was elevated in SSc patients in comparison to controls (p = 0.007) with the highest difference for diffuseSSc (p = 0.004) with significantly elevated mRSS. No association between PPAR-γ levels and hs-CRP, internal organ and vascular involvement, disease duration, autoantibodies and RP onset was found.

Conclusions: The present study revealed elevated serum PPAR-γ in SSc patients, in particular those with a diffuse form, presenting highest mRSS and lowest BMI. Whether circulating PPAR-γ originates from atrophic adipose tissue, reperfused vessels or ischemic tissues needs assessing. Also the biological meaning or effect of elevated serum PPAR-γ requires further studies.

Keywords: fibrosis; organ involvement; peroxisome proliferator-activated receptor γ; pits; systemic sclerosis.

Figure 1

Elevated PPAR-γ concentration in the SSc group vs. healthy control group at p = 0.007. The patients group was divided into limited cutaneous SSc (lcSSc) and diffuse cutaneous SSc (dcSSc). The most significant difference in PPAR-γ concentration was noticed between healthy and dc-SSc at p = 0.004, whilst for lcSSc it reached p = 0.04