Search tips
Search criteria

Results 1-7 (7)

Clipboard (0)

Select a Filter Below

Year of Publication
Document Types
1.  High IL-17E and Low IL-17C Dermal Expression Identifies a Fibrosis-Specific Motif Common to Morphea and Systemic Sclerosis 
PLoS ONE  2014;9(8):e105008.
High interleukin (IL)-17A levels are characteristically found in the skin of systemic sclerosis (SSc) individuals. Our aim was to investigate whether the dermal expression of IL-17A and related IL-17 family members (i.e. IL-17C, IL-17E and IL-17F) could distinguish fibrotic from healthy skin and could show similarities in SSc and morphea, two disorders with presumed distinct pathogenesis, but characterized by skin fibrosis.
Biopsies were obtained from the involved skin of 14 SSc, 5 morphea and 8 healthy donors (HD) undergoing plastic surgery. Immunohistochemistry/immunofluorescence techniques were coupled to a semi-automated imaging quantification approach to determine the presence of the IL-17 family members in the skin. The in vitro effects induced by the IL-17 family members on fibroblasts from normal and SSc individuals were assessed by ELISA and RIA.
Positive cells for each of the IL-17 isoforms investigated were present in the dermis of all the individuals tested, though with variable frequencies. SSc individuals had increased frequency of IL-17A+ (p = 0.0237) and decreased frequency of IL-17F+ (p = 0.0127) and IL-17C+ cells (p = 0.0008) when compared to HD. Similarly, morphea individuals had less frequent IL-17C+ cells (p = 0.0186) in their skin but showed similar number of IL-17A+ and IL-17F+ cells when compared to HD. Finally, IL-17E+ cells were more numerous in morphea (p = 0.0109) and tended to be more frequent in SSc than in HD. Fibroblast production of IL-6, MMP-1 and MCP-1 was enhanced in a dose-dependent manner in the presence of IL-17E and IL-17F, but not in the presence of IL-17C. None of the cytokine tested had significant effect on type I collagen production. Of interest, in SSc the frequency of both IL-17A and IL-17F positive cells increased with disease duration.
The frequency of IL-17A and IL-17F distinguish SSc to morphea individuals while dermal expression of IL-17C (low) and IL-17E (high) identifies a fibrosis-specific motif. The specific IL-17C/IL-17E cytokine combination may thus play a role in the development of fibrosis.
PMCID: PMC4138152  PMID: 25136988
2.  Early systemic sclerosis: marker autoantibodies and videocapillaroscopy patterns are each associated with distinct clinical, functional and cellular activation markers 
Early systemic sclerosis (SSc) is characterized by Raynaud's phenomenon together with scleroderma marker autoantibodies and/or a scleroderma pattern at capillaroscopy and no other distinctive feature of SSc. Patients presenting with marker autoantibodies plus a capillaroscopic scleroderma pattern seem to evolve into definite SSc more frequently than patients with either feature. Whether early SSc patients with only marker autoantibodies or capillaroscopic positivity differ in any aspect at presentation is unclear.
Seventy-one consecutive early SSc patients were investigated for preclinical cardiopulmonary alterations. Out of these, 44 patients and 25 controls affected by osteoarthritis or primary fibromyalgia syndrome were also investigated for serum markers of fibroblast (carboxyterminal propeptide of collagen I), endothelial (soluble E-selectin) and T-cell (soluble IL-2 receptor alpha) activation.
Thirty-two of the 71 patients (45.1%) had both a marker autoantibody and a capillaroscopic scleroderma pattern (subset 1), 16 patients (22.5%) had only a marker autoantibody (subset 2), and 23 patients (32.4%) had only a capillaroscopic scleroderma pattern (subset 3). Patients with marker autoantibodies (n = 48, 67.6%) had a higher prevalence of impaired diffusing lung capacity for carbon monoxide (P = 0.0217) and increased serum levels of carboxyterminal propeptide of collagen I (P = 0.0037), regardless of capillaroscopic alterations. Patients with a capillaroscopic scleroderma pattern (n = 55, 77.5%) had a higher prevalence of puffy fingers (P = 0.0001) and increased serum levels of soluble E-selectin (P = 0.0003) regardless of marker autoantibodies.
These results suggest that the autoantibody and microvascular patterns in early SSc may each be related to different clinical-preclinical features and circulating activation markers at presentation. Longitudinal studies are warranted to investigate whether these subsets undergo a different disease course over time.
PMCID: PMC4060381  PMID: 23718566
Raynaud's phenomenon; early systemic sclerosis; systemic sclerosis marker autoantibodies; nailfold videocapillaroscopy; preclinical organ involvement; puffy fingerscirculating activation markers; carboxyterminal propeptide of collagen I; soluble E-selectin; soluble IL-2 receptor alpha
3.  Quality of life as measured by the short-form 36 (SF-36) questionnaire in patients with early systemic sclerosis and undifferentiated connective tissue disease 
To investigate health-related quality of life (HRQOL) in patients affected by early systemic sclerosis (eSSc) and to compare it with that of patients with undifferentiated connective tissue disease (UCTD).
At baseline, 31 eSSc and 35 UCTD patients underwent clinical evaluation, laboratory investigations, nailfold videocapillaroscopy, echocardiography, and lung function tests. All patients and 40 controls, matched for sex and age completed the Short Form-36 (SF-36) questionnaire and the Health Assessment Questionnaire Disability Index (HAQ-DI).
SF-36 scores were significantly lower in eSSc and UCTD patients than in healthy controls as regards the following domains: physical component score (PCS), mental component score (MCS), physical functioning, role-physical, bodily pain, general health and mental health. PCS was negatively correlated to the HAQ-DI (rho −0.59; p = 0.0004) and ESR >20 mm/h (rho −0.58; p = 0.0006) in eSSc patients. No statistically significant correlation was found between PCS, MCS and HAQ-DI in UCTD patients. Age, sex, disease duration, history of arthritis, low levels of either C3 or C4, a low DLCO (carbon monoxide lung diffusion) and inversion of the E/A ratio were not correlated to PCS and MCS in either eSSc or UCTD patients.
Many eSSc or UCTD patients perceive they have an impaired quality of life in both physical and mental domains. This condition has to be taken into account by the clinicians involved in the care of these patients.
PMCID: PMC3598545  PMID: 23442975
Quality of life; Systemic sclerosis; Undifferentiated connective tissue disease
4.  Early systemic sclerosis: short-term disease evolution and factors predicting the development of new manifestations of organ involvement 
Arthritis Research & Therapy  2012;14(4):R188.
We investigated early systemic sclerosis (SSc) (that is, Raynaud's phenomenon with SSc marker autoantibodies and/or typical capillaroscopic findings and no manifestations other than puffy fingers or arthritis) versus undifferentiated connective tissue disease (UCTD) to identify predictors of short-term disease evolution.
Thirty-nine early SSc and 37 UCTD patients were investigated. At baseline, all patients underwent clinical evaluation, B-mode echocardiography, lung function tests and esophageal manometry to detect preclinical alterations of internal organs, and were re-assessed every year. Twenty-one early SSc and 24 UCTD patients, and 25 controls were also investigated for serum endothelial, T-cell and fibroblast activation markers.
At baseline, 48.7% of early SSc and 37.8% of UCTD patients had at least one preclinical functional alteration (P > 0.05). Ninety-two percent of early SSc patients developed manifestations consistent with definite SSc (that is, skin sclerosis, digital ulcers/scars, two or more teleangectasias, clinically visible nailfold capillaries, cutaneous calcinosis, X-ray bibasilar lung fibrosis, X-ray esophageal dysmotility, ECG signs of myocardial fibrosis and laboratory signs of renal crisis) within five years versus 17.1% of UCTD patients (X2 = 12.26; P = 0.0005). Avascular areas (HR = 4.39 95% CI 1.18 to 16.3; P = 0.02), increased levels of soluble IL-2 receptor alpha (HR = 4.39; 95% CI 1.03 to 18.6; P = 0.03), and of procollagen III aminopropeptide predicted disease evolution (HR = 4.55; 95% CI 1.18 to 17; P = 0.04).
Most early SSc but only a few UCTD patients progress to definite SSc within a short-term follow-up. Measurement of circulating markers of T-cell and fibroblast activation might serve to identify early SSc patients who are more likely to develop features of definite SSc.
PMCID: PMC3580584  PMID: 22901779
6.  Role of MicroRNAs in Fibrosis 
Fibrosis is the leading cause of organ dysfunction in diseases such as systemic sclerosis, liver cirrhosis, cardiac fibrosis, progressive kidney disease, and idiopathic pulmonary fibrosis. The hallmark of fibrosis is tissue remodeling with excess deposition of extracellular matrix components, predominantly collagens. Different cell types, cytokines, growth factors, and enzymes interact in complex pathogenic networks with myofibroblasts playing a pivotal role. MicroRNAs are small non-coding RNAs acting as negative regulators of gene expression at the post-transcriptional level. MicroRNAs have been associated with many basic cellular processes as well as with a wide spectrum of diseases, most notably cancer. This review provides a comprehensive overview of microRNAs regulating profibrotic pathways and extracellular matrix synthesis. The potential of miRNA for targeted therapeutic approaches in fibrotic disorders is also discussed.
PMCID: PMC3396185  PMID: 22802911
Fibrosis; fibroblasts; microRNA (miRNA)-mediated gene regulation regulation; transforming growth factor-beta (TGF-β); connective tissue growth factor (CTGF); extracellular matrix (ECM); epithelial-to-mesenchymal transition (EMT); signaling pathways; antagomirs.
7.  Association of circulating miR-223 and miR-16 with disease activity in patients with early rheumatoid arthritis 
Annals of the Rheumatic Diseases  2013;73(10):1898-1904.
Identification of parameters for early diagnosis and treatment response would be beneficial for patients with early rheumatoid arthritis (ERA) to prevent ongoing joint damage. miRNAs have features of potential biomarkers, and an altered expression of miRNAs was shown in established rheumatoid arthritis (RA).
To analyse RA associated miRNAs in the sera of patients with ERA to find markers of early disease, clinical activity or predictors of disease outcome.
Total RNA was isolated from whole sera in ERA patients (prior to and after 3 and 12 months of therapy with disease modifying antirheumatic drugs), in patients with established RA and in healthy controls (HC) using phenol–chloroform extraction. Expression of miR-146a, miR-155, miR-223, miR-16, miR-203, miR-132 and miR-124a was analysed by TaqMan Real Time PCR.
From all analysed miRNAs, levels of miR-146a, miR-155 and miR-16 were decreased in the sera of ERA patients in comparison with established RA. A change in circulating miR-16 in the first 3 months of therapy was associated with a decrease in DAS28 in long term follow-up in ERA (p=0.002). Levels of circulating miR-223 in treatment naïve ERA correlated with C reactive protein (p=0.008), DAS28 (p=0.031) and change in DAS28 after 3 months (p=0.003) and 12 months (p=0.011) of follow-up. However, neither miR-16 nor miR-223 could distinguish ERA from HC.
Differential expression of circulating miR-146a, miR-155 and miR-16 in the sera of ERA patients may characterise an early stage of the disease. We suggest miR-223 as a marker of disease activity and miR-16 and miR-223 as possible predictors for disease outcome in ERA.
PMCID: PMC4173742  PMID: 23897768
Rheumatoid Arthritis; DAS28; Early Rheumatoid Arthritis

Results 1-7 (7)