scholarly journals Systemic Sclerosis: From Pathophysiology to Novel Therapeutic Approaches

Biomedicines ◽  
2022 ◽  
Vol 10 (1) ◽  
pp. 163
Author(s):  
Devis Benfaremo ◽  
Silvia Svegliati ◽  
Chiara Paolini ◽  
Silvia Agarbati ◽  
Gianluca Moroncini
Keyword(s):  
Immune System ◽  
Systemic Sclerosis ◽  
Plasma Cells ◽  
Clinical Manifestations ◽  
Therapeutic Targets ◽  
Tissue Level ◽  
Internal Organs ◽  
Immune Mediated ◽  
Chronic Disorder ◽  
Substantial Progress

Systemic sclerosis (SSc) is a systemic, immune-mediated chronic disorder characterized by small vessel alterations and progressive fibrosis of the skin and internal organs. The combination of a predisposing genetic background and triggering factors that causes a persistent activation of immune system at microvascular and tissue level is thought to be the pathogenetic driver of SSc. Endothelial alterations with subsequent myofibroblast activation, excessive extracellular matrix (ECM) deposition, and unrestrained tissue fibrosis are the pathogenetic steps responsible for the clinical manifestations of this disease, which can be highly heterogeneous according to the different entity of each pathogenic step in individual subjects. Although substantial progress has been made in the management of SSc in recent years, disease-modifying therapies are still lacking. Several molecular pathways involved in SSc pathogenesis are currently under evaluation as possible therapeutic targets in clinical trials. These include drugs targeting fibrotic and metabolic pathways (e.g., TGF-β, autotaxin/LPA, melanocortin, and mTOR), as well as molecules and cells involved in the persistent activation of the immune system (e.g., IL4/IL13, IL23, JAK/STAT, B cells, and plasma cells). In this review, we provide an overview of the most promising therapeutic targets that could improve the future clinical management of SSc.

scholarly journals Changes in Plasma Phospholipid Metabolism Are Associated with Clinical Manifestations of Systemic Sclerosis

Diagnostics ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 2116
Author(s):  
Marija Geroldinger-Simić ◽  
Thomas Bögl ◽  
Markus Himmelsbach ◽  
Norbert Sepp ◽  
Wolfgang Buchberger
Keyword(s):  
Systemic Sclerosis ◽  
High Performance ◽  
Clinical Manifestations ◽  
Plasma Phospholipid ◽  
Phospholipid Metabolism ◽  
Internal Organs ◽  
New Biomarkers ◽  
First Time

Systemic sclerosis (SSc) is an autoimmune disease with fibrosis of the skin and/or internal organs, causing a decrease in quality of life and survival. There is no causative therapy, and the pathophysiology of the SSc remains unclear. Studies showed that lipid metabolism was relevant for autoimmune diseases, but little is known about the role of lipids in SSc. In the present study, we sought to explore the phospholipid profile of SSc by using the lipidomics approach. We also aimed to analyze lipidomics results for different clinical manifestations of SSc. Experiments were performed using high-performance liquid chromatography coupled to mass spectrometry for the lipidomic profiling of plasma samples from patients with SSc. Our study showed, for the first time, significant changes in the level of phospholipids such as plasmalogens and sphingomyelins from the plasma of SSc patients as compared to controls. Phosphatidylcholine plasmalogens species and sphingomyelins were significantly increased in SSc patients as compared to controls. Our results also demonstrated a significant association of changes in the metabolism of phospholipids (phosphatidylcholine and phosphatidylethanolamine plasmalogens species and sphingomyelins) with different clinical manifestations of SSc. Further lipidomic studies might lead to the detection of lipids as new biomarkers or therapeutic targets of SSc.

scholarly journals Apoptosis Modulation as a Promising Target for Treatment of Systemic Sclerosis

2011 ◽  
Vol 2011 ◽  
pp. 1-13 ◽  
Author(s):  
Stéphane Chabaud ◽  
Véronique J. Moulin
Keyword(s):  
Systemic Sclerosis ◽  
Autoimmune Disease ◽  
Therapeutic Targets ◽  
Immune Dysfunction ◽  
Vascular Damage ◽  
Loss Of Function ◽  
Internal Organs ◽  
Promising Target ◽  
New Findings ◽  
Diffuse Systemic Sclerosis

Diffuse systemic sclerosis (SSc) is a fatal autoimmune disease characterized by an excessive ECM deposition inducing a loss of function of skin and internal organs. Apoptosis is a key mechanism involved in all the stages of the disease: vascular damage, immune dysfunction, and fibrosis. The purpose of this paper is to gather new findings in apoptosis related to SSc, to highlight relations between apoptosis and fibrosis, and to identify new therapeutic targets.

scholarly journals Systemic Sclerosis Pathogenesis and Emerging Therapies, beyond the Fibroblast

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Andrea Sierra-Sepúlveda ◽  
Alexia Esquinca-González ◽  
Sergio A. Benavides-Suárez ◽  
Diego E. Sordo-Lima ◽  
Adrián E. Caballero-Islas ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Immune System ◽  
Systemic Sclerosis ◽  
Autoimmune Disease ◽  
State Of The Art ◽  
Therapeutic Targets ◽  
Organ Damage ◽  
The State ◽  
Pathogenic Mechanism ◽  
Emerging Therapies

Systemic sclerosis (SSc) is a complex rheumatologic autoimmune disease in which inflammation, fibrosis, and vasculopathy share several pathogenic pathways that lead to skin and internal organ damage. Recent findings regarding the participation and interaction of the innate and acquired immune system have led to a better understanding of the pathogenesis of the disease and to the identification of new therapeutic targets, many of which have been tested in preclinical and clinical trials with varying results. In this manuscript, we review the state of the art of the pathogenesis of this disease and discuss the main therapeutic targets related to each pathogenic mechanism that have been discovered so far.

Nanotechnological Strategies as Smart ways for Diagnosis and Treatment of the Atherosclerosis

2019 ◽  
Vol 24 (39) ◽  
pp. 4681-4684 ◽  
Author(s):  
Virna M. Martín Giménez ◽  
Alejandra B. Camargo ◽  
Diego Kassuha ◽  
Walter Manucha
Keyword(s):  
Cardiovascular Disease ◽  
Blood Flow ◽  
Immune System ◽  
Therapeutic Option ◽  
Clinical Manifestations ◽  
Therapeutic Targets ◽  
Atherosclerotic Lesion ◽  
Diagnosis And Treatment ◽  
Drug Supply ◽  
New Therapeutic Targets

Atherosclerosis provokes a continuous worsening of affected vessels causing a blood flow diminution with several complications and with clinical manifestations that generally appear in advanced phases of the illness. Hence, the conventional therapies are not enough because the atherosclerotic injuries are often irrevocable. For this reason, emerges the necessity to implement smart ways of drug supply and develop new therapeutic targets that decrease the advance atherosclerotic lesion. It results due to particular interest to use new tools for prevention, diagnosis, and treatment of this cardiovascular disease, thus concentrating our attention to accomplish better management on the immune system. Finally, this mini-review highlights the most recent knowledge about nanotechnology as a robust, novel and promissory therapeutic option applied to atherosclerotic pathology, nevertheless, we also alert for possible issues associated with their use.

scholarly journals Classical Examples of the Concept of the ASIA Syndrome

Biomolecules ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 1436
Author(s):  
Vânia Borba ◽  
Anna Malkova ◽  
Natalia Basantsova ◽  
Gilad Halpert ◽  
Laura Andreoli ◽  
...  
Keyword(s):  
Immune System ◽  
Clinical Manifestations ◽  
Breast Implants ◽  
Undifferentiated Connective Tissue Disease ◽  
Ptpn22 Gene ◽  
Silicone Breast Implants ◽  
Immune Mediated ◽  
Asia Syndrome ◽  
Skin Biopsies ◽  
Inflammatory Syndrome

Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) was first introduced in 2011 by Shoenfeld et al. and encompasses a cluster of related immune mediated diseases, which develop among genetically prone individuals as a result of adjuvant agent exposure. Since the recognition of ASIA syndrome, more than 4400 documented cases have been reported so far, illustrated by heterogeneous clinical manifestations and severity. In this review, five enigmatic conditions, including sarcoidosis, Sjögren’s syndrome, undifferentiated connective tissue disease, silicone implant incompatibility syndrome (SIIS), and immune-related adverse events (irAEs), are defined as classical examples of ASIA. Certainly, these disorders have been described after an adjuvant stimulus (silicone implantation, drugs, infections, metals, vaccines, etc.) among genetically predisposed individuals (mainly the HLA-DRB1 and PTPN22 gene), which induce an hyperstimulation of the immune system resulting in the production of autoantibodies, eventually leading to the development of autoimmune diseases. Circulating autonomic autoantibodies in the sera of patients with silicone breast implants, as well as anatomopathological aspects of small fiber neuropathy in their skin biopsies have been recently described. To our knowledge, these novel insights serve as a common explanation to the non-specific clinical manifestations reported in patients with ASIA, leading to the redefinition of the ASIA syndrome diagnostic criteria.

scholarly journals Diffuse Systemic Sclerosis with Left Ventricular Diastolic Dysfunction: A Case Report

2019 ◽  
Vol 57 (220) ◽  
Author(s):  
Asmita Neupane ◽  
Prabesh Luintel ◽  
Subodh Sagar Dhakal
Keyword(s):  
Systemic Sclerosis ◽  
Diastolic Dysfunction ◽  
Vascular System ◽  
Left Ventricular Diastolic Dysfunction ◽  
Left Ventricular ◽  
High Morbidity ◽  
Internal Organs ◽  
Immune Mediated ◽  
Diffuse Systemic Sclerosis ◽  
Ventricular Diastolic Dysfunction

Systemic sclerosis is a connective tissue disease characterized by wide-spread vascular lesionsand fibrosis of the skin and internal organs. It is an immune mediated rheumatic disease with thepresence of an immunological dysfunction of T lymphocytes, especially Th1 and Th17 subtypes. Itaffects gastrointestinal, pulmonary, vascular, musculoskeletal, cardiac and various other systems.This disease is rare but has high morbidity and mortality with less known effective management. Wereport a case of 70-year-old female with systemic sclerosis presented with pain along with swellingover multiple joints since 18 months which exacerbated since last 6 months and wound over fingertips since last 2 weeks. We present here other various signs, investigations and management of thisuncommon disease systemic sclerosis, also known as scleroderma. Various systems are evident tobe involved including cardiac (left ventricular diastolic dysfunction) and peripheral vascular system(Raynaud’s phenomenon).

scholarly journals Systemic sclerosis with hemoptysis and a huge lung cavity

2011 ◽  
Vol 1 (4) ◽  
pp. 99
Author(s):  
Attapon Cheepsattayakorn ◽  
Ruangrong Cheepsattayakorn
Keyword(s):  
Systemic Sclerosis ◽  
Raynaud’S Phenomenon ◽  
Clinical Manifestations ◽  
Raynaud's Phenomenon ◽  
Spontaneous Resolution ◽  
Chiang Mai ◽  
Internal Organs ◽  
Mycobacterial Infections ◽  
Thai Woman ◽  
Chest Disease

Systemic sclerosis or scleroderma is associated with distal vasculitis, Raynaud’s phenomenon, and inflammation of internal organs and the skin. We present on a 58-year-old Thai woman with systemic sclerosis who came to the 10th Zonal Tuberculosis and Chest Disease Center, Chiang Mai, Thailand in 2009 and presented with hemoptysis and a solitary hugelung cavity as the predominant clinical manifestations which spontaneously resoluted 2 months later. This case demonstrates a solitary huge-lung cavity with hemoptysis and looked like from non-tuberculous Mycobacterial infections or malignancy with spontaneous resolution of hemoptysis and the lung cavity, which does not need invasive investigations.

Advances in nailfold capillaroscopic analysis in systemic sclerosis

2018 ◽  
Vol 3 (2) ◽  
pp. 122-131 ◽  
Author(s):  
Barbara Ruaro ◽  
Alberto Sulli ◽  
Vanessa Smith ◽  
Carmen Pizzorni ◽  
Sabrina Paolino ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Functional Assessment ◽  
Clinical Manifestations ◽  
Classification Criteria ◽  
Patient Evaluation ◽  
Nailfold Videocapillaroscopy ◽  
Internal Organs ◽  
Microvascular Changes ◽  
Early Diagnose

Systemic sclerosis is an autoimmune connective tissue disease characterized by early and persistent microvascular impairment which leads to functional and organic manifestations, with progressive fibrosis of the skin and internal organs. Morphological and functional assessment of the peripheral microvasculature is a must, not only for diagnosis but also for the prognosis and therapeutical follow-up of systemic sclerosis patients, as reported in recent studies. Nailfold videocapillaroscopy is the validated technique for the study of scleroderma microangiopathy as it is able to detect peripheral microvascular morphology and both classify and score the capillary abnormalities into different microangiopathy patterns (‘Early’, ‘Active’ and ‘Late’). Indeed, the possibility to early diagnose and follow the microvascular changes and the safety of the technique have made nailfold videocapillaroscopy a mandatory tool for patient evaluation and included its assessment in the new systemic sclerosis classification criteria. Important links between nailfold videocapillaroscopy patterns and systemic sclerosis clinical manifestations have been described.

scholarly journals SARS-CoV-2 and Autoimmune Cytopenia

Hemato ◽  
2021 ◽  
Vol 2 (3) ◽  
pp. 463-476
Author(s):  
Ryann Quinn ◽  
Irina Murakhovskaya
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Severe Acute Respiratory Syndrome ◽  
Immune Thrombocytopenic Purpura ◽  
Clinical Course ◽  
Clinical Manifestations ◽  
Thrombocytopenic Purpura ◽  
Immune Mediated ◽  
Autoimmune Cytopenias ◽  
Autoimmune Cytopenia

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with a variety of clinical manifestations related to viral tissue damage, as well as a virally induced immune response. Hyperstimulation of the immune system can serve as a trigger for autoimmunity. Several immune-mediated manifestations have been described in the course of SARS-CoV-2 infection. Immune thrombocytopenic purpura (ITP) and autoimmune hemolytic anemia (AIHA) are the most common hematologic autoimmune disorders seen in the course of SARS-CoV-2 infection. Vaccine-induced thrombocytopenia is a unique autoimmune hematologic cytopenia associated with SARS-CoV-2 vaccination. This paper will review the current literature on the association of SARS-CoV-2 infection and vaccination with autoimmune cytopenias and the clinical course of autoimmune cytopenias in patients with COVID-19.

Progressive multifocal leukoencephalopathy in a patient with systemic sclerosis treated with methotrexate: A case report and literature review

2020 ◽  
Vol 5 (3) ◽  
pp. NP1-NP6 ◽  
Author(s):  
Theodora Simopoulou ◽  
Vana Tsimourtou ◽  
Christina Katsiari ◽  
Marianna Vlychou ◽  
Dimitrios P Bogdanos ◽  
...  
Keyword(s):  
Case Report ◽  
Systemic Sclerosis ◽  
Progressive Multifocal Leukoencephalopathy ◽  
Jc Virus ◽  
Clinical Manifestations ◽  
Immunosuppressive Drugs ◽  
Daily Activities ◽  
Neurological Deficits ◽  
Slow Recovery ◽  
Immune Mediated

Reactivation of viruses occurs in autoimmune disorders in the setting of certain immunosuppressive drugs. We describe a 54-year-old female with systemic sclerosis and extensive cutaneous calcinosis who had been treated with methotrexate for 18 months and presented with headache and neurological deficits. She was diagnosed with progressive multifocal leukoencephalopathy, a rare disease caused by JC virus. Methotrexate was discontinued and mirtazapine plus mefloquine were added. The patient showed a slow recovery and five years later she had complete resolution of progressive multifocal leukoencephalopathy clinical manifestations. Calcinosis had a limited response to various agents and severely affected daily activities of the patient. This case report, highlights the importance of clinical suspicion for progressive multifocal leukoencephalopathy in every patient with immune-mediated disease, even on weak immunosuppressant, who presents with central nervous system manifestations and also the unmet therapeutic need for systemic sclerosis-associated calcinosis.

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