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biomarkers systemic sclerosis

Christelle Sanchez, Gabriel Mazzucchelli, Cécile Lambert, Fanny Comblain, Edwin DePauw, Yves Henrotin
OBJECTIVE: Osteoarthritis (OA) is characterized by cartilage degradation but also by other joint tissues modifications like subchondral bone sclerosis. In this study, we used a proteomic approach to compare secretome of osteoblast isolated from sclerotic (SC) or non sclerotic (NSC) area of OA subchondral bone. DESIGN: Secretome was analyzed using differential quantitative and relative label free analysis on nanoUPLC G2 HDMS system. mRNA of the more differentially secreted proteins were quantified by RT-PCR in cell culture from 5 other patients...
2018: PloS One
Duo Huang, Yang-Yang Cheng, Pak-Hei Chan, Jojo Hai, Kai-Hang Yiu, Hung-Fat Tse, Ka-Lam Wong, Katherine Fan, Ying Wah Li, Woon-Leung Ng, Cheuk-Wan Yim, Cheuk-Hon John Wong, Lai-Shan Tam, Priscilla C H Wong, Chi-Yuen Wong, Chup-Hei Ho, Alexander M H Leung, Chi-Chiu Mok, Ho Lam, Chak-Sing Lau, Tommy Cheung, Carmen Ho, Sharon W Y Law, Esther W Chan, Li-Xue Yin, Wen-Sheng Yue, Toi Meng Mok, Mario Alberto Evora, Chung-Wah Siu
Current guideline-recommended screening for pulmonary hypertension in patients with systemic sclerosis has not been evaluated in systemic lupus erythematosus (SLE), which is disproportionately prevalent in Asians. This multicentre, cross-sectional screening study aims to study the prevalence of pulmonary hypertension among SLE patients using these guidelines, and identify independent predictors and develop a prediction model for pulmonary hypertension in SLE patients. SLE patients from participating centres will undergo an echocardiography- and biomarker-based pulmonary hypertension screening procedure as in the DETECT study...
January 2018: ERJ Open Research
D Kylhammar, R Hesselstrand, S Nielsen, C Scheele, G Rådegran
OBJECTIVE: To identify circulating angiogenic and inflammatory biomarkers with potential in screening for pulmonary arterial hypertension (PAH) in systemic sclerosis (SSc), and in early diagnosis and determination of treatment response in PAH. METHOD: Plasma samples were taken at the time of PAH diagnosis and at treatment follow-up after a median (interquartile range) of 4 months (3-9.8 months) in idiopathic (n = 9) and SSc-associated PAH (n = 11). In patients with SSc-associated PAH, plasma samples had also been gathered a median of 2 years (0...
March 12, 2018: Scandinavian Journal of Rheumatology
Maurizio Cutolo, Amelia C Trombetta, Karin Melsens, Carmen Pizzorni, Alberto Sulli, Barbara Ruaro, Sabrina Paolino, Ellen Deschepper, Vanessa Smith
BACKGROUND: Absolute nailfold capillary number should be a putative biomarker in selected rheumatic diseases but could be time consuming and not highly repeatable. OBJECTIVE: To validate an automated software for absolute nailfold capillary number and density evaluation, on nailfold videocapillaroscopy (NVC) images in systemic sclerosis (SSc). METHODS: An automated software to count nailfold capillary number (AUTOCAPI) had been constructed, through an exploratory image set...
March 12, 2018: Microcirculation: the Official Journal of the Microcirculatory Society, Inc
Kelly M Gillen, Mayyan Mubarak, Thanh D Nguyen, David Pitt
Microglia are resident immune cells that fulfill protective and homeostatic functions in the central nervous system (CNS) but may also promote neurotoxicity in the aged brain and in chronic disease. In multiple sclerosis (MS), an autoimmune demyelinating disease of the CNS, microglia and macrophages contribute to the development of white matter lesions through myelin phagocytosis, and possibly to disease progression through diffuse activation throughout myelinated white matter. In this review, we discuss an additional compartment of myeloid cell activation in MS, i...
2018: Frontiers in Immunology
Anna Lis-Święty, Małgorzata Widuchowska, Ligia Brzezińska-Wcisło, Eugeniusz Kucharz
Objective This study was performed to evaluate the serum amyloid A (SAA) and C-reactive protein (CRP) levels in patients with diffuse systemic sclerosis (dSSc) in relation to a control group, disease duration, and skin and pulmonary involvement. Methods This case-control study included 18 patients with early dSSc, 15 patients with late dSSc, and 15 healthy controls. The SAA and CRP levels, modified Rodnan skin score (mRSS), and diffusing capacity of the lungs for carbon monoxide (DLCO) were determined in all patients...
January 1, 2018: Journal of International Medical Research
Anu Paul, Manuel Comabella, Roopali Gandhi
Multiple sclerosis (MS) is a chronic neurodegenerative autoimmune disease with a complex clinical course characterized by inflammation, demyelination, and axonal degeneration. Diagnosis of MS most commonly includes finding lesions in at least two separate areas of the central nervous system (CNS), including the brain, spinal cord, and optic nerves. In recent years, there has been a remarkable increase in the number of available treatments for MS. An optimal treatment is usually based on a personalized approach determined by an individual patient's prognosis and treatment risks...
March 2, 2018: Cold Spring Harbor Perspectives in Medicine
Sneha M Sundaram, Lorinda Chung
PURPOSE OF REVIEW: This review will summarize the most current literature on the clinical impact, epidemiology, risk factors, screening recommendations, predictors of outcomes, and treatment options in patients with pulmonary arterial hypertension (PAH) associated with systemic sclerosis (SSc). RECENT FINDINGS: PAH continues to be a major cause of morbidity and mortality in SSc. Many risk factors and predictors of outcomes have been identified in patients with SSc including clinical, hemodynamic, and laboratory parameters...
February 27, 2018: Current Rheumatology Reports
Mara Oleszowsky, Matthias F Seidel
Objective: Antinuclear antibodies (ANA) serve as screening tests for connective tissue diseases but have low specificity. In this pilot study, we aimed to identify patients with first-time positive ANA and musculoskeletal complaints and correlate serum soluble vascular adhesion molecules as biomarkers. Methods: Prospective, observational study with 100 ANA-positive patients, comparing them to age- and gender-matched healthy controls (HC, n = 75), was conducted. Serum levels of soluble intercellular adhesion molecule-1 (sICAM-1), endothelial-leukocyte adhesion molecule-1 (sELAM-1), and vascular cell adhesion molecule-1 (sVCAM-1) were measured...
2018: BioMed Research International
Clare Baecher-Allan, Belinda J Kaskow, Howard L Weiner
Multiple sclerosis (MS) is an autoimmune disease triggered by environmental factors that act on a genetically susceptible host. It features three clinical stages: a pre-clinical stage detectable only by MRI; a relapsing-remitting (RRMS) stage characterized by episodes of neurologic dysfunction followed by resolution; and a progressive stage, which usually evolves from the relapsing stage. Advances in our understanding of the immune mechanisms that contribute to MS have led to more than ten FDA-approved immunotherapeutic drugs that target effector T cells, regulatory cells, B cells, and cell trafficking into the nervous system...
February 21, 2018: Neuron
Audrey Benyamine, Xavier Heim, Noémie Resseguier, Daniel Bertin, Carine Gomez, Mikaël Ebbo, Jean-Robert Harlé, Gilles Kaplanski, Pascal Rossi, Nathalie Bardin, Brigitte Granel
OBJECTIVES: We aimed to assess the clinical significance of Krebs von den Lungen-6 (KL-6) in the diagnosis and severity of interstitial lung disease (ILD) in a French cohort of patients with systemic sclerosis (SSc). METHODS: Serum KL-6 concentrations were measured with chemiluminescent enzyme immunoassay (CLEIA) in 75 SSc patients. Patients were divided into two groups according to the presence of interstitial lung disease (SSc-ILD versus SSc-without ILD) on chest High-Resolution Computed Tomography...
February 17, 2018: Rheumatology International
Keita Takahashi, Hideyuki Takeuchi, Yuji Kurihara, Hiroshi Doi, Misako Kunii, Kenichi Tanaka, Haruko Nakamura, Ryoko Fukai, Atsuko Tomita-Katsumoto, Mikiko Tada, Yuichi Higashiyama, Hideto Joki, Shigeru Koyano, Kohtaro Takei, Fumiaki Tanaka
BACKGROUND: Although inflammation in the central nervous system is responsible for multiple neurological diseases, the lack of appropriate biomarkers makes it difficult to evaluate inflammatory activities in these diseases. Therefore, a new biomarker reflecting neuroinflammation is required for accurate diagnosis, appropriate therapy, and comprehension of pathogenesis of these neurological disorders. We previously reported that the cerebrospinal fluid (CSF) concentration of lateral olfactory tract usher substance (LOTUS), which promotes axonal growth as a Nogo receptor 1 antagonist, negatively correlates with disease activity in multiple sclerosis, suggesting that variation in LOTUS reflects the inflammatory activities and is a useful biomarker to evaluate the disease activity...
February 17, 2018: Journal of Neuroinflammation
Dunja Mrdjen, Anto Pavlovic, Felix J Hartmann, Bettina Schreiner, Sebastian G Utz, Brian P Leung, Iva Lelios, Frank L Heppner, Jonathan Kipnis, Doron Merkler, Melanie Greter, Burkhard Becher
Individual reports suggest that the central nervous system (CNS) contains multiple immune cell types with diverse roles in tissue homeostasis, immune defense, and neurological diseases. It has been challenging to map leukocytes across the entire brain, and in particular in pathology, where phenotypic changes and influx of blood-derived cells prevent a clear distinction between reactive leukocyte populations. Here, we applied high-dimensional single-cell mass and fluorescence cytometry, in parallel with genetic fate mapping systems, to identify, locate, and characterize multiple distinct immune populations within the mammalian CNS...
February 6, 2018: Immunity
Elaine O'Loughlin, Charlotte Madore, Hans Lassmann, Oleg Butovsky
Microglia are the resident immune cells that constantly survey the central nervous system. They can adapt to their environment and respond to injury or insult by altering their morphology, phenotype, and functions. It has long been debated whether microglial activation is detrimental or beneficial in multiple sclerosis (MS). Recently, the two opposing yet connected roles of microglial activation have been described with the aid of novel microglial markers, RNA profiling, and in vivo models. In this review, microglial phenotypes and functions in the context of MS will be discussed with evidence from both human pathological studies, in vitro and in vivo models...
February 1, 2018: Cold Spring Harbor Perspectives in Medicine
Stephen P Arnerić, Volker D Kern, Diane T Stephenson
Central Nervous System (CNS) diseases represent one of the most challenging therapeutic areas for successful drug approvals. Developing quantitative biomarkers as Drug Development Tools (DDTs) can catalyze the path to innovative treatments, and improve the chances of drug approvals. Drug development and healthcare management requires sensitive, reliable, validated, and regulatory accepted biomarkers and endpoints. This review highlights the regulatory paths and considerations for developing DDTs required to advance biomarker and endpoint use in clinical development (e...
January 30, 2018: Biochemical Pharmacology
Lucia Chico, Martina Modena, Annalisa Lo Gerfo, Giulia Ricci, Elena Caldarazzo Ienco, Larisa Ryskalin, Francesco Fornai, Gabriele Siciliano
The mechanisms underlying motoneuron degeneration in amyotrophic lateral sclerosis (ALS), a neurodegenerative disorder that affects the motor system with progressive paralysis, are complex and not yet fully understood. It is generally agreed that ALS is a multifactorial and multisystem disease due not only possibly to genetic causes but also to other factors like oxidative stress, mitochondrial dysfunction, protein aggregation, RNA dysmetabolism, autophagy, and excitotoxicity glutamate-mediate. Altered oxidative stress biomarker profile has been repeatedly reported in ALS patients, which may suggest that abnormal free radical production is relevant in the ALS pathogenesis...
December 1, 2017: Archives Italiennes de Biologie
Laura Pellegrino, Martina Coscia, Margit Muller, Claudio Solaro, Maura Casadio
Multiple sclerosis is a chronic, autoimmune and neurodegenerative disease affecting multiple functional systems and resulting in motor impairments associated with muscle weakness and lack of movement coordination. We quantified upper limb motor deficits with a robot-based assessment including behavioral and muscle synergy analysis in 11 multiple sclerosis subjects with mild to moderate upper limb impairment (9 female; 50 ± 10 years) compared to 11 age- and gender- matched controls (9 female; 50 ± 9 years)...
February 1, 2018: Scientific Reports
Tom Gyllenhammar, Mikael Kanski, Henrik Engblom, Dirk M Wuttge, Marcus Carlsson, Roger Hesselstrand, Håkan Arheden
BACKGROUND: Patients with systemic sclerosis (SSc) have high cardiovascular mortality even though there is no or little increase in prevalence of epicardial coronary stenosis. First-pass perfusion on cardiovascular magnetic resonance (CMR) have detected perfusion defects indicative of microvascular disease, but the quantitative extent of hypoperfusion is not known. Therefore, we aimed to determine if patients with SSc have lower global myocardial perfusion (MP) at rest or during adenosine stress, compared to healthy controls, quantified with CMR...
January 30, 2018: BMC Cardiovascular Disorders
Melanie D Sweeney, Abhay P Sagare, Berislav V Zlokovic
The blood-brain barrier (BBB) is a continuous endothelial membrane within brain microvessels that has sealed cell-to-cell contacts and is sheathed by mural vascular cells and perivascular astrocyte end-feet. The BBB protects neurons from factors present in the systemic circulation and maintains the highly regulated CNS internal milieu, which is required for proper synaptic and neuronal functioning. BBB disruption allows influx into the brain of neurotoxic blood-derived debris, cells and microbial pathogens and is associated with inflammatory and immune responses, which can initiate multiple pathways of neurodegeneration...
January 29, 2018: Nature Reviews. Neurology
Eleni Chouri, Nila H Servaas, Cornelis P J Bekker, Alsya J Affandi, Marta Cossu, Maarten R Hillen, Chiara Angiolilli, Jorre S Mertens, Lucas L van den Hoogen, Sandra Silva-Cardoso, Maarten van der Kroef, Nadia Vazirpanah, Catharina G K Wichers, Tiago Carvalheiro, Sofie L M Blokland, Barbara Giovannone, Laura Porretti, Wioleta Marut, Barbara Vigone, Joel A G van Roon, Lorenzo Beretta, Marzia Rossato, Timothy R D J Radstake
OBJECTIVE: MicroRNAs (miRNAs) are regulatory molecules, which have been addressed as potential biomarkers and therapeutic targets in rheumatic diseases. Here, we investigated the miRNA signature in the serum of systemic sclerosis (SSc) patients and we further assessed their expression in early stages of the disease. METHODS: The levels of 758 miRNAs were evaluated in the serum of 26 SSc patients as compared to 9 healthy controls by using an Openarray platform. Three miRNAs were examined in an additional cohort of 107 SSc patients and 24 healthy donors by single qPCR...
January 19, 2018: Journal of Autoimmunity
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