Updates in systemic sclerosis pathogenesis: Toward new therapeutic opportunities.

[Updates in systemic sclerosis pathogenesis: Toward new therapeutic opportunities]. Rev Med Interne. 2019 Jul 10;: Authors: Didier K, Robbins A, Antonicelli F, Pham BN, Giusti D, Servettaz A Abstract Systemic sclerosis is a rare connective tissue disease characterized by skin and several internal organ fibrosis, systemic vasculopathy and immune abnormalities. Even if fibroblasts and endothelial cells dysfunction, as well as lymphocytes and other immune cells implication are now well described, the exact origin and chronology of the disease pathogenesis remain unclear. Oxidative stress, influenced by genetic and environmental factors, seems to play a key role. Indeed, it seems to be implicated in the early phases of fibrosis development, vasculopathy and in immune tolerance abnormalities shared by all patients, although disease expression is heterogeneous. To date, no curative treatment is available. Even if immunosuppressive treatment or drugs acting on vascular system are proposed for some patients, overall, treatment efficiency remains modest. Only autologous hematopoietic stem cells transplantation, reserved for patients with severe or rapidly progressive fibrosis, has recently demonstrated efficiency, with lasting regression of fibrosis. Nevertheless, this treatment can expose to important, life-threatening toxicity. In the last decade, new mechanisms implicated in the pathogenesis of systemic sclerosis have been unraveled, bringing new therapeutic op...
Source: Revue de Medecine Interne - Category: Internal Medicine Tags: Rev Med Interne Source Type: research

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AbstractThree prospective controlled clinical trials and numerous small series and case reports have confirmed that durable, drug-free remission in systemic sclerosis is possible via an autologous hematopoietic stem cell transplantation. Similar results have been seen in other autoimmune diseases. The exact mechanism by which this immune “reset” was achieved in some but not all cases remains elusive, but includes major reduction of autoreactive immune competent cells, re-establishment of T- and B cell regulatory networks and normalization of tissue niche function, particularly vascular. Some aspects regarding m...
Source: BioDrugs - Category: Drugs & Pharmacology Source Type: research
Contributors : Shervin Assassi ; Xuan Wang ; Guocai Chen ; Ellen A Goldmuntz ; Lynette Keyes-Elstein ; Jun Ying ; Paul K Wallace ; Jacob Turner ; W J Zheng ; Virginia Pascual ; John Varga ; Monique E Hinchcliff ; Chiara Bellocchi ; Peter McSweeney ; Daniel E Furst ; Rechard A Nash ; Leslie J Crofford ; Beverly Welch ; Ashely Pinckney ; Maureen D Mayes ; Keith M SullivanSeries Type : Expression profiling by arrayOrganism : Homo sapiensThis is global gene expression study of whole blood samples collected in the Cyclophosphamide Or Transplantation (SCOT) randomized controlled trial, as well as unaffected controls.Patients wit...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by array Homo sapiens Source Type: research
In a time where new immunomodulatory therapies are widely available, it seems remarkable that the number of hematopoietic stem cell transplantations (HSCT) performed in rheumatic diseases is still increasing. However, in progressive systemic sclerosis, autologous HSCT is the only treatment with proven survival benefits. In refractory cases of inflammatory arthritis, systemic lupus erythematosus, and several other rare rheumatic conditions, HSCT contributed to better disease control as well. Nevertheless, HSCT is still associated with considerable risks, and a careful balancing of benefits and risks remains paramount.
Source: Rheumatic Disease Clinics of North America - Category: Rheumatology Authors: Source Type: research
CONCLUSION: In general, worldwide expert agreement on updated recommendations for treatment of SSc is high, supporting their value. Differences in agreement are partially explained by geographical area and treatment availability. PMID: 31043545 [PubMed - as supplied by publisher]
Source: J Rheumatol - Category: Rheumatology Authors: Tags: J Rheumatol Source Type: research
Autologous hematopoietic stem cell transplantation (aHSCT) is performed in patients with aggressive forms of systemic sclerosis (SSc). The profile of B cell reconstitution after aHSCT is not fully understood. ...
Source: Arthritis Research and Therapy - Category: Rheumatology Authors: Tags: Research article Source Type: research
Scleroderma is one of the main clinical features of chronic graft-versus-host disease (cGVHD), in which donor immune cells react against host tissues after allogeneic hematopoietic stem cell transplant. It has been reported that interferon (IFN)- γ released by donor T cells promotes infiltration of donor T cells themselves into the skin, and mediates production of transforming growth factor (TGF)-β from macrophages in the pathogenesis of sclerodermatous cGVHD. To investigate the roles of host keratinocytes, which are the targets for donor T cells, in skin fibrosis of cGVHD, we established a new murine model of s...
Source: Journal of Investigative Dermatology - Category: Dermatology Authors: Tags: Adaptive and Auto-Immunity Source Type: research
Qiancheng Deng1, Yangyang Luo1,2, Christopher Chang3, Haijing Wu1, Yan Ding4* and Rong Xiao1* 1Hunan Key Laboratory of Medical Epigenetics, Department of Dermatology, The Second Xiangya Hospital, Central South University, Changsha, China 2Department of Dermatology, Hunan Children's Hospital, Changsha, China 3Division of Rheumatology, Allergy and Clinical Immunology, University of California, Davis, Davis, CA, United States 4Department of Dermatology, Hainan Provincial Dermatology Disease Hospital, Haikou, China Autoimmune diseases are usually complex and multifactorial, characterized by aberrant produc...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
The objectives of this report were: to present a short review on morphological (nailfold videocapillaroscopy, NVC) and functional techniques (laser tools and thermography) that allow for a correct diagnosis and treatment of RP and to investigate blood perfusion (BP) by laser speckle contrast analysis (LASCA) in different skin areas of hands and face in PRP, SRP to SSc, and healthy subjects (CNT). Methods: 31 PRP patients (LeRoy criteria), 70 SRP to SSc (ACR/EULAR criteria) and 68 CNT were enrolled. BP was assessed by LASCA at the level different areas of hands and face. NVC was performed to distinguish between PRP and SRP...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Purpose of review To review the recently published data and provide a practical overview for management of systemic sclerosis-interstitial lung disease (SSc-ILD). Recent findings Published evidence shows considerable practitioner variability in screening patients for ILD. Recent published data support use of cyclophosphamide or mycophenolate mofetil as first-line treatment of SSc-ILD. For patients not responding to first-line therapies, consideration is given to rituximab as rescue therapy. Recent trials of hematopoietic autologous stem cell transplantation have demonstrated benefit in patients with progressive SSc-IL...
Source: Current Opinion in Rheumatology - Category: Rheumatology Tags: CLINICAL THERAPEUTICS & HEMATOLOGIC COMPLICATIONS: Edited by W. Joseph McCune Source Type: research
We describe the challenges in treating a previously well 5-year-old male who has refractory symptoms of DPMC. Over the 29  months, since his initial presentation, we trialed over ten therapies. There was subjective improvement with prednisolone and mycophenolate mofetil (MMF). However, other therapies including biologics and tyrosine kinase inhibitors (TKI) were ineffective. The patient has been referred for hematopoi etic stem cell transplant given ongoing disease progression. We conducted a literature search focusing on English articles with keywords including DPMC. Publications with limited information or describin...
Source: Rheumatology International - Category: Rheumatology Source Type: research
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