Pathophysiology of systemic sclerosis: current understanding and new insights.

Pathophysiology of systemic sclerosis: current understanding and new insights. Expert Rev Clin Immunol. 2019 May 03;: Authors: Cutolo M, Soldano S, Smith V Abstract INTRODUCTION: Systemic sclerosis (SSc) is a complex autoimmune connective tissue disease characterized by chronic and progressive tissue and organ fibrosis with broad patient-to-patient variability. Some risk factors are known and include combination of persistent Raynaud's phenomenon, steroid hormone imbalance, selected chemicals, thermal or other injuries. Endogenous and/or exogenous environmental trigger/risk factors promote epigenetic mechanisms in genetically primed subjects. Disease pathogenesis presents early microvascular changes with endothelial cell dysfunction, followed by the activation of mechanisms promoting their transition into myofibroblasts. A complex autoimmune response, involving innate and adaptive immunity with specific/functional autoantibody production, characterizes the disease. Progressive fibrosis and ischemia involve skin and visceral organs resulting in their irreversible damage/failure. Progenitor circulating cells (monocytes and fibrocytes), together with growth factors and cytokines participate in disease diffusion and evolution. Epigenetic, vascular and immunologic mechanisms implicated in systemic fibrosis, represent major targets for incoming disease modifying therapeutic approaches. Areas covered: This review discusses the current understanding of SSc pathog...
Source: Expert Review of Clinical Immunology - Category: Allergy & Immunology Tags: Expert Rev Clin Immunol Source Type: research

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Purpose of review To summarize recent advances in the understanding of the pathogenesis of autoimmune fibrotic diseases. These diseases include IgG4-related disease, systemic sclerosis and lupus nephritis. Recent findings Recent studies indicate that a poorly studied subset of helper T cells, cytotoxic CD4+ T cells and sub-populations of disease-specific activated B cells infiltrate inflamed tissues and collaborate to induce tissue fibrosis in autoimmune fibrotic diseases. Cycles of apoptosis induced by antigen-specific cytotoxic CD4+ T cells followed by macrophage-mediated clearing of apoptotic cells and finally tiss...
Source: Current Opinion in Rheumatology - Category: Rheumatology Tags: RAYNAUD PHENOMENON, SCLERODERMA, OVERLAP SYNDROMES AND OTHER FIBROSING SYNDROMES: Edited by John Varga Source Type: research
Abstract Systemic sclerosis is a complex autoimmune connective tissue disease which carries a significant burden of disease-related morbidity including potentially life-threatening complications. Systemic sclerosis can affect all the major organs and therefore, although the disease is uncommon, many hospital-based specialists are involved in patient care. Vascular disease (e.g. Raynaud's phenomenon) is an almost universal symptom in patients with systemic sclerosis and is often the earliest manifestation of the disease. Systemic sclerosis not uncommonly can overlap with other rheumatological conditions (e.g. rheum...
Source: British Journal of Hospital Medicine - Category: Internal Medicine Authors: Tags: Br J Hosp Med (Lond) Source Type: research
AbstractRaynaud ’s phenomenon (RP) is used to describe a symptom complex caused by digital vascular compromise. RP is a clinical diagnosis. The typically episodic nature of RP has resulted in a reliance upon patient self-report for diagnosis. The term ‘primary RP’ is generally applied when no underlying patho logy can be demonstrated. Whilst ‘primary RP’ is currently considered a distinct disorder, there is evidence that the term may comprise several entities that include a functional vasospastic disorder, a physiologically appropriate thermoregulatory response, subclinical atherosclerosis and...
Source: Clinical Rheumatology - Category: Rheumatology Source Type: research
This report has basically focused on scleroderma renal crisis (SRC), which is the most serious renal manifestation of SSc, characterized by renal failure and sudden onset of hypertension. A 44-year-old man was hospitalized with hypertension, headache, vertigo, nausea, rhinorrhea, reflux, dysphagia, dyspnea (Fc II), visual impairment, mechanical arthralgia, and edema (+3) accompanied by a rare skin lesion. Raynaud's phenomenon was also remarkable in fingers and toes. According to signs and symptoms, SSc diagnosed and the proper treatment was applied. It is of great importance that in the case of malignant hypertension in pa...
Source: Iranian Journal of Kidney Diseases - Category: Urology & Nephrology Tags: Iran J Kidney Dis Source Type: research
Osman K. Yilmaz1, Stefanie Haeberle1, Meifeng Zhang1, Marvin J. Fritzler2, Alexander H. Enk1 and Eva N. Hadaschik1,3* 1Department of Dermatology, University of Heidelberg, Heidelberg, Germany 2Mitogen Advanced Diagnostics Laboratory, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada 3Department of Dermatology, University Hospital of Essen, Essen, Germany Due to a missense mutation in the Foxp3 gene, scurfy mice are deficient in functional regulatory T cells (Treg). The consequent loss of peripheral tolerance manifests itself by fatal autoimmune mediated multi-organ disease. Previous studies...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Scleroderma is a group of autoimmune diseases characterized by increased collagen synthesis and deposition within connective tissue. The skin disease can be classified into two major groups: localized and systemic scleroderma. Localized scleroderma differs from systemic scleroderma in that it involves only the skin. Systemic scleroderma, also known as systemic sclerosis, may affect any organ system.1 Systemic sclerosis is often differentiated from localized scleroderma early by the development of Raynaud ’s phenomenon, or paroxysmal vasospasm induced by cold or stress, which is the first sign in the vast majority of ...
Source: Journal of Oral and Maxillofacial Surgery - Category: ENT & OMF Authors: Tags: Case Report Source Type: research
ConclusionOur study confirmed that many ACA ‐positive cases can be classified into an autoimmune disease type on presentation.
Source: International Journal of Rheumatic Diseases - Category: Rheumatology Authors: Tags: ORIGINAL ARTICLE Source Type: research
Purpose of review Systemic sclerosis is a systemic autoimmune disorder wherein interstitial lung disease (ILD) is the major source or morbidity and mortality. Research into mechanisms of fibrosis and its intersection with autoimmunity, specifically lung fibrosis, has accelerated and been applied to autoimmune disorders such as scleroderma. This review highlights important emerging insights and treatment trials. Recent findings The important elements of this review focus on the challenges faced in identifying patients not only who develop lung disease but who are at a higher risk for progression given the heterogeneous...
Source: Current Opinion in Rheumatology - Category: Rheumatology Tags: RAYNAUD PHENOMENON, SCLERODERMA, OVERLAP SYNDROMES AND OTHER FIBROSING SYNDROMES: Edited by John Varga Source Type: research
Purpose of review Systemic sclerosis (SSc) is an autoimmune connective tissue disease in which inflammation and cytokine dysregulation leads to skin fibrosis. Toll-like receptors (TLRs) are conserved pattern recognition receptors, recognizing pathogens danger-associated molecular patterns (DAMPs) that elicit a cascade of proinflammatory signaling. Recently, TLRs have been found to be critically important in SSc pathogenesis, with increased levels of the TLRs and their ligands present in the disease. Animal models have also been pivotal in delineating the role of these innate immune receptors in SSc. This current review e...
Source: Current Opinion in Rheumatology - Category: Rheumatology Tags: RAYNAUD PHENOMENON, SCLERODERMA, OVERLAP SYNDROMES AND OTHER FIBROSING SYNDROMES: Edited by John Varga Source Type: research
We examined the regulation of HIF-1α, its target heme oxygenase-1 (HMOX-1), and the serum levels of the HIF-1α protein in a subset of patients as well as in ten healthy individuals. The expression of HIF-1α and HMOX-1 in monocytes was measured using absolute plasmid-based quantitative real-time PCR, whereas serum HIF-1α levels were measured with ELISA. Samples were taken at the time of randomization and after 24 weeks. We found that HIF-1α and HMOX-1 mRNA expression in monocytes and serum HIF-1α protein levels were significantly higher in the SS/RS patients compared to the healthy contro...
Source: Acta Pharmacologica Sinica - Category: Drugs & Pharmacology Authors: Tags: Acta Pharmacol Sin Source Type: research
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