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Update on the Gastrointestinal Microbiome in Systemic Sclerosis.
Bellocchi, C, Volkmann, ER
Current rheumatology reports. 2018;(8):49
Abstract
PURPOSE OF REVIEW Accumulating evidence suggests that gut microbiota affect the development and function of the immune system and may play a role in the pathogenesis of autoimmune diseases. The purpose of this review is to summarize recent studies reporting gastrointestinal microbiota aberrations associated with the systemic sclerosis disease state. RECENT FINDINGS The studies described herein have identified common changes in gut microbial composition. Specifically, patients with SSc have decreased abundance of beneficial commensal genera (e.g., Faecalibacterium, Clostridium, and Bacteroides) and increased abundance of pathobiont genera (e.g., Fusobacterium, Prevotella, Erwinia). In addition, some studies have linked specific genera with the severity of gastrointestinal symptoms in systemic sclerosis. More research is needed to further characterize the gastrointestinal microbiota in systemic sclerosis and understand how microbiota perturbations can affect inflammation, fibrosis, and clinical outcomes. Interventional studies aimed at addressing/correcting these perturbations, either through dietary modification, pro/pre-biotic supplementation, or fecal transplantation, may lead to improved outcomes for patients with systemic sclerosis.
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[Vitamin D metabolism and osteoporosis in systemic sclerosis].
Szamosi, S, Horváth, Á, Szekanecz, Z, Szűcs, G
Orvosi hetilap. 2017;(32):1252-1258
Abstract
In the past few years more and more data have become available on the important role of vitamin D in immunological processes and inflammation. The role of vitamin D deficiency in the pathogenesis as well as in disease progression of different autoimmune and inflammatory conditions is suspected. Vitamin D deficiency is prevalent in several autoimmune diseases, including systemic sclerosis. Hypovitaminosis has been found to be associated with low bone mineral density and higher prevalence of osteoporosis in this group of patients. Determinants of low bone density in SSc are poorly understood. Studies have shown the importance of both traditional osteoporotic as well as disease-specific factors (extent of skin involvement, presence of internal organ manifestation, malabsorption, systemic sclerosis subtype, serological profile, medication) in the development of low bone mineral density. The relationship between low bone density in systemic sclerosis patients and the above mentioned risk factors may be more complex and the real role of each factor is unclear. Yet very few studies reported clinically relevant low bone mass outcomes such as fracture risk assessment and fracture associated mortality in scleroderma. This review aims to synthesize data about the essential role of vitamin D in immune homeostasis as well as the prevalence of hypovitaminosis, low bone density, changes in bone turnover markers and presence of osteoporosis in scleroderma patients. Orv Hetil. 2017; 158(32): 1252-1258.
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Intestinal microbiome in scleroderma: recent progress.
Volkmann, ER
Current opinion in rheumatology. 2017;(6):553-560
Abstract
PURPOSE OF REVIEW Our evolving understanding of how gut microbiota affects immune function and homeostasis has led many investigators to explore the potentially pathologic role of gut microbiota in autoimmune diseases. This review will discuss the rapidly advancing field of microbiome research in systemic sclerosis (SSc), an incurable autoimmune disease with significant gastrointestinal morbidity and mortality. RECENT FINDINGS Recent reports have identified common perturbations in gut microbiota across different SSc cohorts. Compared with healthy controls, patients with SSc have decreased abundance of beneficial commensal genera (e.g. Faecalibacterium, Clostridium and Bacteroides) and increased abundance of pathbiont genera (e.g. Fusobacterium, Prevotella and Erwinia). Certain genera may protect against (e.g. Bacteroides, Clostridium, and Lactobacillus), or conversely exacerbate (e.g. Fusobacterium and Prevotella) gastrointestinal symptoms in SSc. These genera represent potential targets to avert or treat gastrointestinal dysfunction in SSc. SUMMARY Emerging evidence suggests that alterations in gut microbiota exist in the SSc disease state; however, future basic and clinical studies are needed to ascertain the mechanism by which these alterations perpetuate inflammation and fibrosis in SSc. Therapeutic trials are also needed to investigate whether dietary interventions or fecal transplantation can restore the gut microbial balance and improve health outcomes in SSc. VIDEO ABSTRACT http://links.lww.com/COR/A38.
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Micronutrients, their potential effect on patients with systemic sclerosis.
Wan, YN, Yan, JW, Peng, WJ, Zhang, JQ, Xiao, CC, Wang, BX, Wang, J
Modern rheumatology. 2014;(5):709-14
Abstract
Over the past years, several evidences have supported an important role of specific micronutrients, including vitamin A, vitamin D and vitamin E in immune dysfunction, vascular involvement and fibrotic changes involved in systemic sclerosis (SSc) development. In PubMed, eight clinical trials about the therapy of micronutrients on SSc patients were searched out using medical subject headings terms (SSc: "scleroderma, localized", "scleroderma, systemic", "scleroderma, diffuse" and "scleroderma, limited"; vitamins "vitamin A", "thiamin", "riboflavin", "niacin", "pantothenic acid", "vitamin B 6", "biotin", "folic acid", "vitamin B 12", "inositol", "choline", "ascorbic acid", "vitamin D", "vitamin E", "tocopherols", "vitamin K" and "vitamin P"; and minerals: "calcium", "magnesium", "potassium", "sodium", "phosphorus", "sulfur", "chlorine", "iron", "copper", "iodine", "zinc", "selenium", "manganese", "molybdenum", "cobalt", "chromium", "tin", "vanadium", "silicon", "nickel" and "fluorine"). This brief review will summarize current understanding on that for the further prospect of future studies. Though the clinical trials for the treatment of SSc with micronutrients are still in their infancy, more researches are needed to substantiate the current results and accelerate the knowledge in this field.
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Prospective study to evaluate the association between systemic sclerosis and occupational exposure and review of the literature.
Marie, I, Gehanno, JF, Bubenheim, M, Duval-Modeste, AB, Joly, P, Dominique, S, Bravard, P, Noël, D, Cailleux, AF, Weber, J, et al
Autoimmunity reviews. 2014;(2):151-6
Abstract
INTRODUCTION Systemic sclerosis (SSc) has complex pathogenesis and likely multifactorial causes. Environmental exposures have been suggested to play a role in SSc pathogenesis, including occupational exposure to pollutants and chemicals as well as use of drugs leading to modulation of immune response. Thus, this case-control study aimed to assess: the relationship between SSc and occupational exposure; and the risk of SSc related to occupational exposure in male and female patients. METHODS From 2005 to 2008, 100 patients with a definite diagnosis of SSc were included in the study; 3 age, gender, and smoking habits matched controls were selected for each patient. A committee of experts evaluated blindly occupational exposure to crystalline silica, white spirit, organic solvents, ketones, welding fumes, epoxy resins, and pesticides; an occupational exposure score was calculated for all subjects. Our findings were compared with previous data in the literature. RESULTS Increased ORs for SSc were found for: crystalline silica (p<0.0001), white spirit (p<0.0001), aromatic solvents (p=0.0002), chlorinated solvents (p=0.014), trichlorethylene (p=0.044), ketones (p=0.002) and welding fumes (p=0.021). Elevated risk associated with high final cumulative score in SSc was observed for: crystalline silica, white spirit, chlorinated solvents, trichlorethylene, aromatic solvents, any type of solvents, ketones and welding fumes. A marked association between SSc and occupational exposure was further found for: 1) crystalline silica, chlorinated solvents, trichloroethylene, white spirit, ketones and welding fumes in male patients; and 2) white spirit, aromatic solvents, any type of solvent and ketones in female patients. Finally, we did not find an association between SSc and: 1) the use of drugs that have been speculated to play a role in SSc onset (anorexigens, pentazocine, bromocriptine, l-tryptophan); 2) implants - that are prosthesis, silicone implants, and contact lenses; and 3) dyeing hair. In the literature, SSc has been associated with occupational exposure to silica and solvents, while the association between SSc and specific organic solvents and welding fumes has been anecdotally reported. CONCLUSION The following occupational factors have an impact in the development of SSc: crystalline silica, white spirit, aromatic solvents, chlorinated solvents, trichlorethylene, ketones and welding fumes. The risk of SSc appears to be markedly associated with high cumulative exposure. Finally, the association between SSc and occupational exposure may be variable according to gender.
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[Transfer RNA-associated anti-Wa antibody in patients with scleroderma and the target antigen NEFA/Nucleobindin-2].
Imura, Y, Mimori, T
Nihon Rinsho Men'eki Gakkai kaishi = Japanese journal of clinical immunology. 2007;(3):151-5
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Abstract
Many autoantibodies associated with nucleic acids are found in autoimmune diseases, and are important for analyzing pathophysiologic mechanisms. Toll-like receptors (TLRs) are receptor molecules for innate immunity and some of them recognize nucleic acids. Nucleic acids in autoantigens may stimulate TLR and activate antigen presenting cells as adjuvants. The Wa antigen was found as a transfer RNA (tRNA)-binding protein by RNA immunoprecipitation and identified as NEFA/Nucleobindin-2. Although the function of NEFA/Nucleobindin-2 is still not clear, it may be involved in secretion of proteins along with calcium metabolism and in protein translation by tRNA-binding ability.
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Treatment of systemic sclerosis.
Allanore, Y, Kahan, A
Joint bone spine. 2006;(4):363-8
Abstract
Systemic sclerosis is the most severe of all connective tissue diseases. The distinctive pathogenic process involves sequential or concomitant abnormalities in blood vessel function, immunity and, ultimately, fibroblast function. These specific characteristics may explain the results of treatment evaluations. The decrease in excess mortality shown in recent studies seems chiefly ascribable to the use of cardiovascular drugs. Angiotensin-converting enzyme (ACE) inhibitors are effective in resolving renal crisis, prostacyclins and endothelin antagonists improve pulmonary hypertension, and calcium antagonists and ACE inhibitors benefit patients with myocardial involvement. On the other hand, immunomodulatory drugs and other agents investigated for their disease-modifying potential failed to influence skin fibrosis in controlled trials. Trials of immunosuppressants are ongoing. Available results indicate that emphasis should be put on cardiovascular drugs. The development of criteria for disease activity and severity would facilitate future research on the treatment of systemic sclerosis.