Comparative analysis of affected and unaffected areas of systemic sclerosis skin biopsies by high-throughput proteomic approaches

Objective. To determine active TGF-β1 (aTGF-β1) levels in serum, skin, and peripheral blood mononuclear cell (PBMC) culture supernatants and to understand their associations with clinical parameters in systemic sclerosis (SSc) patients.Methods. We evaluated serum samples from 56 SSc patients and 24 healthy controls (HC). In 20 SSc patients, we quantified spontaneous or anti-CD3/CD28 stimulated production of aTGF-β1 by PBMC. The aTGF-β1 levels were measured by ELISA. Skin biopsies were obtained from 13 SSc patients and six HC, and TGFB1 expression was analyzed by RT-PCR.Results. TGF-β1 serum levels were significantly higher in SSc patients than in HC (p< 0.0001). Patients with increased TGF-β1 serum levels were more likely to have diffuse subset (p= 0.02), digital ulcers (p= 0.02), lung fibrosis (p< 0.0001), positive antitopoisomerase I (p= 0.03), and higher modified Rodnan score (p= 0.046). Most of our culture supernatant samples had undetectable levels of TGF-β1. No significant difference in TGFB1 expression was observed in the SSc skin compared with HC skin.Conclusion. Raised active TGF-β1 serum levels and their association with clinical manifestations in scleroderma patients suggest that this cytokine could be a marker of fibrotic and vascular involvement in SSc.

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An open-label study to evaluate biomarkers and safety in systemic sclerosis patients treated with paquinimod

Arthritis Research & Therapy ◽

10.1186/s13075-021-02573-0 ◽

2021 ◽

Vol 23 (1) ◽

Author(s):

Roger Hesselstrand ◽

Jörg H. W. Distler ◽

Gabriela Riemekasten ◽

Dirk M. Wuttge ◽

Marie Törngren ◽

...

Keyword(s):

Systemic Sclerosis ◽

Type I ◽

Type I Ifn ◽

Open Label ◽

Reactive Protein ◽

Before And After ◽

Modified Rodnan Skin Score ◽

Skin Biopsies ◽

Rank 2

Abstract Objectives To evaluate the changes in disease-related biomarkers and safety of paquinimod, an oral immunomodulatory compound, in patients with systemic sclerosis (SSc). Methods In this open-label, single-arm, multicenter study, SSc patients with a rapidly progressive disease received paquinimod for 8 weeks. Blood and skin biopsies were collected at baseline, during treatment, and at follow-up for the analyses of type I interferon (IFN) activity, chemokine (C-C motif) ligand 2 (CCL2), and the number of myofibroblasts. The safety of paquinimod was evaluated throughout the study. Results Nine SSc patients were enrolled and completed the study treatment with paquinimod at 3 mg/day for 8 weeks. After the treatment, a reduction of type I IFN activity in the plasma from one patient with elevated baseline IFN activity was recorded. A trend towards reduced IFN activity in the skin after treatment was also observed in patients. The serum level of CCL2 was reduced in 7 of 9 patients after paquinimod treatment. There was a median reduction of 10% of the number of myofibroblasts in skin biopsies at week 8 compared to baseline. No change in modified Rodnan skin score and quality of life was detected in the study. Reported adverse events (AEs) were mild to moderate and expected with the most common being arthralgia (n = 3) and headache (n = 3), and C-reactive protein (CRP) increase. Conclusions Analysis of biomarkers before and after treatment suggest reduced type I IFN activity and reduced number of myofibroblasts in lesional skin. Paquinimod was overall well tolerated with mild to moderate and expected AEs. Trial registration ClinicalTrials.gov, NCT01487551. Registered on 7 September 2011

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Comparative analysis of paddy straw-degrading consortia in China using high-throughput sequencing

Applied Soil Ecology ◽

10.1016/j.apsoil.2021.104077 ◽

2021 ◽

Vol 167 ◽

pp. 104077

Author(s):

Yunhe Ban ◽

Xiang Li ◽

Yuqi Li ◽

Xinyu Li ◽

Xu Li ◽

...

Keyword(s):

Comparative Analysis ◽

High Throughput ◽

High Throughput Sequencing ◽

Paddy Straw

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HLA-G Expression in the Skin of Patients with Systemic Sclerosis

The Journal of Rheumatology ◽

10.3899/jrheum.080552 ◽

2009 ◽

Vol 36 (6) ◽

pp. 1230-1234 ◽

Cited By ~ 24

Author(s):

ISABELA J. WASTOWSKI ◽

PERCIVAL D. SAMPAIO-BARROS ◽

ELIANE M.I. AMSTALDEN ◽

GUSTAVO MARTELLI PALOMINO ◽

JOÃO FRANCISCO MARQUES-NETO ◽

...

Keyword(s):

Systemic Sclerosis ◽

Control Sample ◽

Healthy Controls ◽

Skin Disorders ◽

Disease Prognosis ◽

Laboratory Variables ◽

Skin Biopsies ◽

Dermal Cells

Objective.To determine HLA-G expression in skin biopsies from patients with systemic sclerosis (SSc), and its association with epidemiological, clinical, and laboratory variables and survival.Methods.Paraffin-embedded skin biopsies obtained from 21 SSc patients (14 limited SSc, 7 diffuse SSc) and from 28 healthy controls were studied. HLA-G expression was evaluated by immunohistochemistry.Results.HLA-G molecules were detected in 57% of skin biopsies from patients with SSc (9 from limited SSc, 3 from diffuse SSc), whereas no control sample expressed HLA-G (p = 0.000004). In patients, HLA-G molecules were consistently observed within epidermal and some dermal cells. HLA-G expression was associated with a lower frequency of vascular cutaneous ulcers (p = 0.0004), telangiectasias (p = 0.008), and inflammatory polyarthralgia (p = 0.02). After a 15-year followup, SSc patients who exhibited HLA-G survived longer than patients who did not.Conclusion.HLA-G is expressed in skin biopsies from patients with SSc, and this is associated with a better disease prognosis. This suggests a modulatory role of HLA-G in SSc, as observed in other skin disorders.

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