Early Stages Of Systemic Sclerosis Research Articles

Traditional Chinese Medicine Integrated Responsive Microneedles for Systemic Sclerosis Treatment

Traditional Chinese medicine, such as Tripterygium wilfordii and Paeonia lactiflora, has potential values in treating systemic sclerosis (SSc) and other autoimmune diseases, while their toxic side effect elimination and precise tropical drug delivery are still challenges. Here, we present multiple traditional Chinese medicine integrated photoresponsive black phosphorus (BP) microneedles (MNs) with the desired features for the SSc treatment. By employing a template-assisted layer-by-layer curing method, such MNs with triptolide (TP)/paeoniflorin (Pae) needle tips and BP-hydrogel needle bottoms could be well generated. The combined administration of TP and Pae can not only provide anti-inflammatory, detoxification, and immunomodulatory effects to treat skin lesions in the early stage of SSc but also remarkably reduce the toxicity of single drug delivery. Besides, the additive BPs possess good biocompatibility and near-infrared (NIR) responsiveness, imparting the MN photothermal-controlled drug release capability. Based on these features, we have demonstrated that the traditional Chinese medicine integrated responsive MNs could effectively improve skin fibrosis and telangiectasia, reduce collagen deposition, and reduce epidermal thickness in the SSc mouse models. These results indicated that the proposed Chinese medicine integrated responsive MNs had enormous potential in clinical therapy of SSc and other diseases.

Effects of the Mechanism of Traditional Chinese Medical Prescription-Yiqihuoxue Formula on Vasculopathy with Systemic Sclerosis

Vasculopathy is a prevalent complication that may appear in the early stage of Systemic Sclerosis (SSc). Traditional Chinese medical prescription-Yiqihuoxue formula (YQHX) has been used as a therapeutic option for SSc in our department, which has acquired a significant treatment effect. We interrogated the role of the YQHX on Vasculopathy with SSc by investigating its effects on the HDMECs from H2O2 injury. The viability of the HDMECs which were induced by H2O2 and then impacted by the YQHX was noticeably more than that of the H2O2-induced HDMECs, while the apoptosis cell percentage was significantly lower. The YQHX could promote cell proliferation and inhibit apoptosis which meant it could protect HDMECs from H2O2 injury. And the tube formation assay shown that the YQHX may have a promoted effects on angiogenic properties of HDMECs. Our data demonstrated that the YQHX is helpful on alleviating vasculopathy. These data help in directing personalized therapeutic approaches in SSc.

Role of B-Cell in the Pathogenesis of Systemic Sclerosis.

Systemic sclerosis (SSc) is a rare multisystem autoimmune disease, characterized by fibrosis, vasculopathy, and autoimmunity. Recent advances have highlighted the significant implications of B-cells in SSc. B-cells are present in affected organs, their subpopulations are disrupted, and they display an activated phenotype, and the regulatory capacities of B-cells are impaired, as illustrated by the decrease in the IL-10+ producing B-cell subpopulation or the inhibitory membrane co-receptor density. Recent multi-omics evidence highlights the role of B-cells mainly in the early stage of SSc and preferentially during severe organ involvement. This dysregulated homeostasis partly explains the synthesis of anti-endothelial cell autoantibodies (AECAs) or anti-fibroblast autoantibodies (AFAs), proinflammatory or profibrotic cytokines (interleukin-6 and transforming growth factor-β) produced by B and plasma cells. That is associated with cell-to-cell interactions with endothelial cells, fibroblasts, vascular smooth muscle cells, and other immune cells, altogether leading to cell activation and proliferation, cell resistance to apoptosis, the impairment of regulatory mechanisms, and causing fibrosis of several organs encountered in the SSc. Finally, alongside these exploratory data, treatments targeting B-cells, through their depletion by cytotoxicity (anti-CD20 monoclonal antibody), or the cytokines produced by the B-cell, or their costimulation molecules, seem interesting, probably in certain profiles of early patients with severe organic damage.

AB0662 Elevated fecal calprotectin in early systemic sclerosis

BackgroundGastrointestinal (GI) morbidity is prevalent in systemic sclerosis (SSc), causing a reduction in quality of life and increased mortality, but has been difficult to assess objectively [1]. Elevated levels of fecal calprotectin (F-cal), a biomarker of GI inflammation, has previously been observed in patients with SSc [2]. F-cal has not been explored in early SSc and its diagnostic potential in the classification of SSc has not been studied.ObjectivesOur objectives were; 1) study F-cal levels in early SSc; 2) investigate the discriminatory power of F-cal; 3) explore F-cal in relation to GI features of SSc.MethodsConsecutive referred patients with suspected new-onset SSc without concurrent non-SSc GI disease were invited to this study. Patients were classified as SSc if meeting ACR-EULAR criteria, or SSc mimickers if they did not. GI symptoms and use of NSAID or PPI was noted. F-cal was measured and levels >50ug/g were classified as elevated. F-cal was also measured in age- and sex matched controls without rheumatological disease.ResultsOf 137 patients, 92 were classified as SSc and 45 as SSc mimickers. Elevated F-cal was significantly more common in SSc patients compared to the control group (38% vs 7.3%; p < 0.001) but not compared to the SSc mimicker patients (38% vs 31%; p = 0.427). The median F-cal level was higher in SSc patients compared to controls (35 µg/g vs ≤30 µg/g; p ≤ 0.001) but not compared to the SSc mimicker patients (35 µg/g vs ≤30 µg/g; p = 0.248). Elevated F-cal was not associated with any GI symptoms. Elevated F-cal was more common in patients who used PPI (OR 7.14; 95% CI 2.56-29.93; p < 0.001).ConclusionIn this study, we demonstrate that elevated levels of F-cal are prevalent already in the early stages of SSc. These results are in line with previous data suggesting that GI involvement may be present in early SSc.Table 1.Frequency of GI features and association to F-cal elevation (n = 92)GI features (n, %)Normal F-cal, n = 57Elevated F-cal, n = 35Odds Ratio (95% CI)Dysphagia19 (35%)12 (34%)0.99 (0.41-2.41)Reflux symptoms33 (59%)23 (68%)1.46 (0.60-3.56)Fecal incontinence9 (16%)3 (8.6%)0.50 (0.08-2.22)Patient-reported involuntary weightloss11 (20%)8 (23%)1.21 (0.43-3.39)Dilated esophagus on HRCT8 (16%)8 (28%)1.95 (0.64-5.94)NSAID use12 (21%)6 (17%)0.78 (0.26-2.30)PPI use23 (40%)29 (83%)7.14 (2.56-19.93)Figure 1.F-cal measurements by group. Median value represented by horizontal bar.

Raynaud’s Phenomenon with Focus on Systemic Sclerosis

Raynaud’s phenomenon is a painful vascular condition in which abnormal vasoconstriction of the digital arteries causes blanching of the skin. The treatment approach can vary depending on the underlying cause of disease. Raynaud’s phenomenon can present as a primary symptom, in which there is no evidence of underlying disease, or secondary to a range of medical conditions or therapies. Systemic sclerosis is one of the most frequent causes of secondary Raynaud’s phenomenon; its appearance may occur long before other signs and symptoms. Timely, accurate identification of secondary Raynaud’s phenomenon may accelerate a final diagnosis and positively alter prognosis. Capillaroscopy is fundamental in the diagnosis and differentiation of primary and secondary Raynaud’s phenomenon. It is helpful in the very early stages of systemic sclerosis, along with its role in disease monitoring. An extensive range of pharmacotherapies with various routes of administration are available for Raynaud’s phenomenon but a standardized therapeutic plan is still lacking. This review provides insight into recent advances in the understanding of Raynaud’s phenomenon pathophysiology, diagnostic methods, and treatment approaches.

Management of Endothelial Dysfunction in Systemic Sclerosis: Current and Developing Strategies.

Systemic Sclerosis (SSc) is an autoimmune disease marked by dysregulation of the immune system, tissue fibrosis and dysfunction of the vasculature. Vascular damage, remodeling and inadequate endothelial repair are hallmarks of the disease. Since early stages of SSc, damage and apoptosis of endothelial cells (ECs) can lead to perivascular inflammation, oxidative stress and tissue hypoxia, resulting in multiple clinical manifestations. Raynaud's phenomenon, edematous puffy hands, digital ulcers, pulmonary artery hypertension, erectile dysfunction, scleroderma renal crisis and heart involvement severely affect quality of life and survival. Understanding pathogenic aspects and biomarkers that reflect endothelial damage in SSc is essential to guide therapeutic interventions. Treatment approaches described for SSc-associated vasculopathy include pharmacological options to improve blood flow and tissue perfusion and, more recently, cellular therapy to enhance endothelial repair, promote angiogenesis and heal injuries. This mini-review examines the current knowledge on cellular and molecular aspects of SSc vasculopathy, as well as established and developing therapeutic approaches for improving the vascular compartment.

Identification of Autoimmunity to Peptides of Collagen V α1 Chain as Newly Biomarkers of Early Stage of Systemic Sclerosis.

Patients with Systemic sclerosis (SSc) presents immune dysregulation, vasculopathy, and fibrosis of the skin and various internal organs. Pulmonary fibrosis leads to SSc-associated interstitial lung disease (ILD), which is the main cause of morbidity and mortality in SSc. Recently autoimmunity to type V collagen (Col V) has been characterized in idiopathic pulmonary fibrosis and show promise to be related to the development in SSc. Our aim was to evaluate autoimmunity to Col V α1(V) and α2(V) chains and to the antigenic peptides of these Col V chains in early-SSc sera employing lung tissue of SSc-ILD, as antigen source. We found that sera samples from patients with early-SSc were reactive to Col V (41.18%) and presented immunoreactivity for Col5A1(1.049) and Col5A1(1.439) peptides. The IgG isolated from early-SSc patients-anti-Col V positive sera (anti-ColV IgG) was adsorbed with α1(V) chain (anti-ColV IgG/ads-α1(V)) and α2(V) chain (anti-ColV IgG/ads-α2(V)) and biotinylated to evaluate the spectrum of reactivity in SSc-ILD patients lung biopsies by immunofluorescence. The SSc-ILD lung tissue samples immunostained with anti-ColV IgG showed increased green fluorescence in the vascular basement membrane, bronchiolar smooth muscle, and adventitial layer, contrasting with the tenue immunostaining in control lungs. Col V protein expression in these pulmonary compartments immunostained with early-SSc anti-ColV IgG was confirmed by immune colocalization assays with commercial anti-human Col V antibodies. In addition, SSc-ILD lung tissues immunostained with anti-ColV IgG/ads-α1(V) (sample in which Col V α1 chain-specific antibodies were removed) showed decreased green fluorescence compared to anti-ColV IgG and anti-ColV IgG/ads-α2(V). Our data show that autoimmunity to Col V in early-SSc was related to peptides of the α1(V) chain, suggesting that these antibodies could be biomarkers of SSc stages and potential target of immunotherapy with Col V immunogenic peptides.

Challenges in the management of oral manifestations in a patient with limited systemic sclerosis

Background: Limited systemic sclerosis (SSc), or scleroderma, is characterized by widespread vasculopathy, excessive multiorgan fibrosis, and autoantibody. The early stages of SSc are challenging to diagnose because of their similarity to other autoimmune conditions. Inappropriate SSc treatment can increase the risk of disability, morbidity, and mortality. Different pathogenesis pathways incur various manifestations in the skin and the oral cavity. In this scenario, dentists play an essential role in managing oral SSc manifestations. Proper oral examination, diagnosis, and therapy help to increase the confidence and patient’s quality of life. Case Report: A 24-year-old female patient with SSc was referred from the Internal Medicine Department to the Oral Medicine Department because of lip soreness for 2 weeks, resulting in difficulty eating and opening the mouth. A complete anamnesis and clinical examination were done. The patient was diagnosed with an oral ulcer caused by SSc, cheilitis exfoliative, drug-induced pigmentation, xerostomia, and acute pseudomembranous candidiasis. The oral lesion in this patient was concluded as an oral ulcer caused by SSc because the patient had already stopped using methotrexate for 2 weeks before the ulceration appeared. The oral treatment included sodium chloride (NaCl 0.9%), vaseline album, hyaluronic acid mouthwash, and nystatin. Oral lesions had a significant improvement after 3 days of treatment. Conclusion: The SSc manifestation that appeared on the oral cavity of the patient as microstomia, tongue stiffness, and oral ulcer resulted in inadequate clinical examination, and diagnosis. Treatments for this oral SSc were challenging.

Abnormalities of heart rate turbulence and heart rate variability as indicators of increased cardiovascular risk in patients with systemic sclerosis.

IntroductionSystemic sclerosis (SSc) is a connective tissue disease manifested by progressive fibrosis of many internal organs including the cardiovascular system and development of autonomic disorders with sympathetic predominance. These abnormalities can increase cardiovascular mortality.AimTo evaluate heart rate turbulence (HRT) and variability (HRV) parameters (indicator of autonomic imbalance) obtained from 24-hour ECG Holter monitoring, as predictors of the increased cardiovascular risk in patients with scleroderma.Material and methodsThirty-twoscleroderma patients and 30 healthy people were included. After clinical examination, ECG, routine laboratory tests and echocardiography, participants performed 24-hour Holter-ECG at home. For HRT assessment, turbulence onset (To) and turbulence slope (Ts) parameters were used. Both time and frequency domain analysis of HRV was used. The HRV circadian rhythm was also evaluated.ResultsTime domain: SDNN, SDNN-ix, SDANN and frequency domain: LF, VLF, ULF, NHF, NLF, parameters were lower, while p50NN was higher in SSc as compared to the control group. There was also a loss of the circadian rhythm for r-MSSD and p50NN present in the control group. Abnormal HRT parameters To and/or Ts occurred in the SSc group only. The median value of To = –1.24% and Ts = 11.13 ms/RR did not differ significantly as compared to the control group.ConclusionsThe study confirmed the presence of HRV disturbances, including HRV circadian rhythm, as it may seem at an early stage of SSc. The HRT disorders may be characterized by the increasing changes with advancing disease. This indicates the presence of autonomic imbalance and an increased cardiovascular risk.

Differences associated with age at onset in early systemic sclerosis patients: a report from the EULAR Scleroderma Trials and Research Group (EUSTAR) database

Objective: The aim of this study was to analyse differences in clinical presentation in patients with early (< 3 years’ duration) systemic sclerosis (SSc), comparing three age groups according to disease subsets.Method: Cross-sectional analysis of the prospective EULAR Scleroderma Trials and Research database (EUSTAR) was performed. Patients fulfilling preliminary American College of Rheumatology 1980 classification criteria for SSc, with < 3 years from the first non-Raynaud’s SSc symptom at first entry, were selected. Patients with < 3 years from the first SSc symptom, including Raynaud’s phenomenon, were also analysed. SSc-related variables, including antibodies, SSc subsets, and organ involvement, were examined. Age was categorized into ≤ 30, 31–59, and ≥ 60 years. We performed descriptive and bivariate analyses.Results: The study included 1027 patients: 90% Caucasian, 80% women, and 40% with diffuse disease. In early stages of SSc, younger patients had significantly more anti-Scl-70 antibodies and diffuse disease. With increasing age, we observed more elevation of estimated pulmonary systolic pressure on echocardiography (5%, 13%, and 30%, respectively, in the three age groups), cardiac conduction blocks (6%, 6%, and 15%), and left ventricular diastolic dysfunction (4%, 12%, and 27%). The results were similar for 650 patients with < 3 years from first SSc symptom, including Raynaud’s.Conclusion: In early stages of SSc, older patients showed data indicating more severe disease with greater cardiac involvement. The diffuse subset was more frequent in the younger subgroup. The identification of such differences may help in selecting appropriate management for individual patients in clinical practice.

Skin manifestations of patients with systemic sclerosis and their clinical significance

Objective To investigate features of skin lesions of patients with systemic sclerosis (SSc) , and to analyze the relationship of skin manifestations with clinical classification, autoantibodies and internal organ involvement. Methods Clinical data were collected from 120 patients with SSc in Department of Dermatology of Zhongshan Hospital Affiliated to Fudan University and Department of Scleroderma of Shanghai TCM-integrated Hospital between 2012 and 2014, and analyzed retrospectively. Results Among the 120 patients with SSc, 118 (98.3%) had Raynaud′s phenomenon, 116 (96.7%) had skin sclerosis, including 101 (84.2%) with sclerosis of skin over the dorsum of fingers, 90 (75%) had swollen skin, including 84 (70%) with swollen fingers, 77 (64.2%) had poikiloderma, 75 (62.5%) had thinned lip, 74 (61.7%) had telangiectasia, 63 (52.5%) had radial furrowing around the mouth, 57 (47.5%) had mask-like face, 49 (40.8%) had hyperplasia of nail cuticle, 35 (29.2%) had petechiae of the nailfolds, 25 (20.8%) had depressed fingertip, 24 (20.0%) had atrophy of the finger pulp, 24 (20.0%) had distal finger shortening, and 15 (12.5%) had fingertip ulcer. Anti-Scl-70 antibody and anti-centromere antibody (ACA) were positive in 42 (35.0%) and 31 (25.8%) patients respectively. The incidence of swollen fingers, fingertip ulcer, atrophy of the finger pulp was significantly higher in the anti-Scl-70 antibody- positive group than in the-negative group (P < 0.05) , and the incidence of sclerosis of skin over the dorsum of fingers, poikiloderma, fingertip ulcer and atrophy of the finger pulp was all significantly higher in the anti-Scl-70 antibody-positive group than in the ACA-positive group (P < 0.05) . The main internal organ involvement included interstitial lung disease (50%, 44/88) , cardiac involvement (47.8%, 55/115) , pulmonary arterial hypertension (35.7%, 41/115) , esophageal involvement (28.3%, 34/120) and kidney involvement (9.2%, 11/120) . Patients with diffuse cutaneous systemic sclerosis (dcSSc) showed significantly higher incidence of cardiac involvement and poikiloderma compared with those with limited cutaneous systemic sclerosis (lcSSc) (P < 0.01) . Swollen fingers, sclerosis of skin over the dorsum of fingers, poikiloderma, telangiectasia, lip thinning, and radial furrowing around the mouth most commonly occurred in patients with early SSc, and swollen fingers and sclerosis of skin over the dorsum of fingers were highly correlated with the occurrence of pulmonary arterial hypertension. Telangiectasia, depressed fingertip and fingertip ulcer were significantly correlated with the occurrence of interstitial lung disease, and atrophy of the finger pulp was significantly correlated with the occurrence of cardiac involvement (both P < 0.05) . Conclusions Raynaud′s phenomenon, swollen fingers, sclerosis of skin over the dorsum of fingers, poikiloderma, telangiectasia, lip thinning and radial furrowing around the mouth can be helpful for the early diagnosis of SSc. Pulmonary arterial hypertension commonly occurs in the early stage of SSc. Depressed fingertip and fingertip ulcer indicate the occurrence of interstitial lung disease, and the atrophy of the finger pulp indicates cardiac involvement. Key words: Scleroderma, systemic; Skin manifestations; Antoantibodies; Early diagnosis; Fibrosis; Internal organs

Autoimmune myocarditis in systemic sclerosis: an unusual form of scleroderma heart disease presentation

Primary cardiac involvement in systemic sclerosis is common, often subclinical, and is associated with significant mortality. We report the case of a patient who developed autoimmune myocarditis at an early stage of systemic sclerosis, who completely recovered from cardiac dysfunction under optimal medical therapy for heart failure and immunosuppression. This challenging case aims at increasing awareness around the fact that the heart is a target organ of scleroderma disease. It also highlights the importance of screening and early diagnosis of cardiac involvement, because a timely treatment may impact the quality of life of these patients and improve their prognosis.

The magnitude of cytokine production by stimulated CD56+ cells is associated with early stages of systemic sclerosis

Immune activation is a hallmark of systemic sclerosis (SSc). However, the immunological alterations that occur in preclinical and non-fibrotic SSc and that differentiate these subjects from those with primary Raynaud's phenomenon (PRP) or healthy controls (HC) are poorly defined. We isolated CD56+ (NK/NKT-like) cells from HC, patients with PRP, early SSc (EaSSc) and definite SSc without skin or lung fibrosis. Cytokine production upon different activating stimuli was measured via a multiplex immuno assay. Clearly discriminative patterns among the different stages of SSc were most markedly observed after TLR1/2 stimulation, with increased IL-6, TNF-α and MIP-1α/CCL3 production in definite SSc patients as compared to HC and/or PRP. Initial alterations were observed in EaSSc patients with an intermediate secretion pattern between HC/PRP and definite SSc. CD56+ cells from patients at different stages of SSc differentially respond to TLR stimulation, highlighting the relevance of natural immunity in the developmental and pre-fibrotic SSc.

Possible association of elevated serum collagen type IV level with skin sclerosis in systemic sclerosis.

Collagen type IV is the primary collagen in the basement membranes around blood vessels and in the dermoepidermal junction in the skin. Perivascular collagen type IV is synthesized by endothelial cells and pericytes, and contributes to the homeostasis and remodeling of blood vessels. It has been well recognized that elevated serum collagen type IV levels are associated with the liver fibrosis. The objective was to examine serum collagen type IV levels and their clinical associations in patients with systemic sclerosis (SSc), and to examine the expression of collagen type IV in the fibrotic skin in SSc. Serum collagen type IV levels in SSc patients and diffuse cutaneous type SSc patients were significantly higher than those in healthy individuals. Serum collagen type IV levels were positively correlated with modified Rodnan total skin score. Serum collagen type IV levels in early stage (disease duration ≤3 years) diffuse cutaneous SSc patients were significantly elevated. Serum collagen type IV levels in SSc patients with digital ulcers (DU) were significantly elevated. In immunohistochemical staining, the expression of collagen type IV around dermal small vessels in the affected skin was reduced compared with those of normal individuals. These results suggest that elevated serum collagen type IV levels may be associated with the skin sclerosis in the early stage of SSc. The measurement of serum collagen type IV levels in SSc patients may be useful as a disease activity marker in skin sclerosis and DU.

The Modified Hand Mobility in Scleroderma Test and Skin Involvement - A Followup Study.

To study the change in the modified Hand Mobility in Scleroderma (mHAMIS) test from early to advanced stages of systemic sclerosis (SSc), and the relationship between mHAMIS and skin involvement during followup. This retrospective study includes 65 patients with baseline disease duration of ≤ 3 years who were assessed with the mHAMIS test at baseline and at 1 or 2 predefined followup points (3.1-5 yrs and 5.1-9 yrs after disease onset). Studied measures were the modified Rodnan skin score (mRSS), mRSS of the hand, serum cartilage oligomeric matrix protein, and digital vascular lesions. The mHAMIS and the mRSS hand changed synchronously during the first 5 years after disease onset (rs = 0.44, p = 0.001). In the group with high mHAMIS at baseline, both mHAMIS and mRSS hand improved significantly at the first followup (p < 0.05), and the improvement sustained during the followup in the mRSS hand. Patients with antitopoisomerase I and anti-RNA polymerase III antibodies had significantly higher mHAMIS at baseline (p = 0.003) and at the second followup (p = 0.030) compared to patients with anticentromere antibodies. Patients with digital vascular lesions at baseline had significantly higher mHAMIS during the followup (p < 0.05) compared to patients without. The mHAMIS improved significantly during the followup in patients with immunosuppressive treatment in early disease (p < 0.05), but not in patients without this treatment. The mHAMIS reflects disease activity in fibrosis in early stages of SSc. In later stages it can be regarded as a measure of damage arising from fibrotic and vascular involvement, making it suitable as an endpoint in followup examinations.

Rapid, noninvasive quantitation of skin disease in systemic sclerosis using optical coherence elastography.

Systemic sclerosis (SSc) is a connective tissue disease that results in excessive accumulation of collagen in the skin and internal organs. Overall, SSc has a rare morbidity (276 cases per million adults in the United States), but has a 10-year survival rate of 55%. Currently, the modified Rodnan skin score (mRSS) is assessed by palpation on 17 sites on the body. However, the mRSS assessed score is subjective and may be influenced by the experience of the rheumatologists. In addition, the inherent elasticity of skin may bias the mRSS assessment in the early stage of SSc, such as oedematous. Optical coherence elastography (OCE) is a rapidly emerging technique, which can assess mechanical contrast in tissues with micrometer spatial resolution. In this work, the OCE technique is applied to assess the mechanical properties of skin in both control and bleomycin (BLM) induced SSc-like disease noninvasively. Young’s modulus of the BLM-SSc skin was found be significantly higher than that of normal skin, in both the in vivo and in vitro studies (p<0.05 p<0.05 ). Thus, OCE is able to differentiate healthy and fibrotic skin using mechanical contrast. It is a promising new technology for quantifying skin involvement in SSc in a rapid, unbiased, and noninvasive manner.

Decreased numbers of endothelial progenitor cells in patients in the early stages of systemic sclerosis

IntroductionMicroangiopathy and endothelial dysfunction are present in the early stages of systemic sclerosis (SSc). Defective vasculogenesis mediated by bone marrow-derived endothelial progenitor cells (EPCs) might be involved in the vascular abnormalities found in SSc. ObjectivesTo evaluate the circulating EPC levels and EPC subtypes via flow cytometry and early outgrowth colony-forming units (CFUs) in patients with SSc compared to healthy subjects. MethodsThirty-nine female SSc patients (30 in the early stages of SSc) and 44 age-matched healthy women were included. Peripheral blood EPCs were quantified using flow cytometry and by counting the early outgrowth CFUs. ResultsThe EPCs quantified with flow cytometry and the CFU numbers were significantly lower in SSc patients than in control subjects (155.1±95.1 vs. 241.3±184.2 EPC/106 lymphomononuclear cells, p=0.011; 15.4±8.6 vs. 23.5±10.9CFU, p<0.001; respectively), as well as in the group of patients in the early stages of SSc compared to the controls. Patients with digital ulcers had significantly higher CFU counts than those without ulcers (p=0.013). Among patients with the scleroderma pattern on nailfold capillaroscopy, patients with the late pattern had significantly lower EPC levels than those with the early and active patterns (p=0.046). There were no significant correlations of EPCs or CFU levels with RP duration. ConclusionsThe present study revealed decreased EPCs in SSc patients, including those with early disease onset. These findings suggest that defective vasculogenesis occurs in the early phases of the disease. Therefore, EPCs might be an important therapeutic target for the prevention of vascular complications in SSc patients.

FRI0512 Involvement of Plexind1/Semaphorin 3E Pathway in the Dysregulation of Vascular Tone Control in Systemic Sclerosis Patients

BackgroundThe main hallmark of systemic sclerosis (SSc) is vasculopathy characterised by dysregulation of angiogenesis and vascular tone leading to loss of capillaries. The vascular and nervous system have several anatomic...

A10.27 Systemic Sclerosis – Role of Agonistic Autoantibodies Directed Against the Angiotensin Receptor Type 1 and the Endothelin Receptor Type A on Immune Cells in Disease Pathogenesis

Background and ObjectivesAgonistic autoantibodies against the angiotensin receptor type 1 (AT1R) and the endothelin receptor type A (ETAR) have been identified in the majority of systemic sclerosis (SSc) patients. We...

N-acetylcysteine infusion reduces the resistance index of renal artery in the early stage of systemic sclerosis

To evaluate resistance index (RI) changes in renal artery after N-acetylcysteine infusion in patients with systemic sclerosis. In an open-label study 40 patients with systemic sclerosis (SSc) were treated with N-acetylcysteine (NAC) iv infusion over 5 consecutive hours, at a dose of 0.015 g x kg(-1) x h(-1). Renal haemodynamic effects were evaluated by color Doppler examination before and after NAC infusion. NAC infusion significantly reduced RI in a group of sclerodermic patients with early/active capillaroscopic pattern, modified Rodnan Total Skin Score (mRTSS) <14 and mild-moderate score to the vascular domain of Medsger Scleroderma Disease Severity Scale (DSS). RI increased after NAC infusion in patients with late capillaroscopic pattern, mTRSS>14 and severe-end stage score to the vascular domain of DSS. In patients with reduction of RI after NAC infusion, diffusion capacity for carbon monoxide mean value was significantly higher than in those patients with an increase of RI. No significant differences in renal blood flow were found between patients with different subsets of SSc. In patients with low disease severity NAC ameliorates vascular renal function.