| What Causes Scleroderma? | | The cause of scleroderma is largely unknown, but here is some interesting research. | |
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What Causes Scleroderma? |
| The cause of scleroderma is generally unknown, however areas being investigated include autoimmunity, environmental exposures, genetics, and infections. Many researchers feel that several factors work together to induce scleroderma, such as a genetic inclination along with exposure to a toxin or infection which triggers the illness. |
| Scleroderma is not believed to be contagious; you cannot get it by hugging or kissing someone or other intimate contact. |
| There is an increased incidence of certain types other autoimmune diseases and cancer among scleroderma patients. (Also see: Associated Conditions) |
| The Immunobiology of Systemic Sclerosis. The SSc hallmarks of vascular damage, immunologic activation, and collagen deposition can be traced to 4 major factors: T-cells, fibroblasts, B-cells, and cytokines/chemokines. Significant variations in laboratory data among patients suggest that the pathology reflects a heterogeneous disease. PubMed. Seminars in Arthritis and Rheumatism. 02/13/08. (Also see: B and T cells, Fibroblasts, and Cytokines) |
| Advanced Glycation Endproducts (AGES) |
| Expression of advanced glycation end products and their receptor in skin from patients with systemic sclerosis (SSc) with and without calcinosis. Our results indicate the possible contribution of AGE-CML [N{epsilon}-(carboxymethyl) lysine] deposition on the extracellular matrix in the dermis of the limited SSc with extracellular matrix subgroup to the pathogenesis of formation of calcinotic deposits. Christine A. Davies. Rheumatology. June 19, 2009. (Also see: Calcinosis) |
| Artificial Joints and Silicone Breast Implants |
| Causes of Scleroderma: Artificial Joints and Silicone Breast Implants. Are some cases of connective tissue disease, such as scleroderma, related to artificial joints or silicone breast implants? Contradictory findings continue to plague research into this area. ISN. |
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| Autoimmunity |
| Causes of Scleroderma: Autoimmunity Scleroderma appears to be an autoimmune disease, in which the immune system attacks the body itself, causing an overproduction of collagen. ISN. |
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| Autoimmunity: B Cells and T Cells |
| Autoimmunity: B Cells and T Cells. T Cells are white blood cells that help stimulate an immune response to infections. Sometimes T cells become overactive, which is suspected as being part of the process that leads to autoimmune diseases. ISN. |
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| Cluster Studies |
| Causes of Scleroderma: Cluster Studies Cluster studies can help pinpoint some of the causes of scleroderma. ISN. |
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| Cytokines |
| Cytokines are small secreted proteins which mediate and regulate immunity, inflammation, and hematopoiesis. Cytokines can cause inflammation associated with a variety of autoimmune diseases. ISN. |
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| Dendritic Cells |
| Dendritic cells are involved in the regulation of the body's immune system response, and are thought to be a key to preventing or treating autoimmune diseases. ISN. |
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| Drugs and Medications |
| Causes of Scleroderma: Drugs and Medications Some medications and street drugs are known or thought to induce scleroderma or Raynaud's, such as Bleomycin, Cocaine, Marijuana, and Paclitaxel (Taxanes). ISN. |
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| Endothelin |
| Endothelin and Systemic Scleroderma. Endothelin is a protein that helps to regulate contraction and relaxation of the smooth muscle found in the walls of blood vessels and internal organs (except the heart). An overproduction of endothelin, whether by illness or medication, can cause blood vessels to constrict and blood pressure to increase. In scleroderma, it can cause pulmonary arterial hypertension. ISN. |
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| Environmental |
| Causes of Scleroderma: Environmental Topics covered include exposure to cadmium, mercury (dental amalgam), solvents (such as paint thinners), radiation, and silica as either known or suspected causes of autoimmune disease or scleroderma. ISN. |
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| Fetal Cells and Scleroderma |
| Causes of Scleroderma: Fetal Cells Fetal cells as a cause of scleroderma is a hot topic of research and discussion lately. And since the topic is filled with intriguing possibilities, cutting-edge science, and unanswered questions, there is likewise some inescapable controversy. ISN. |
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| Fibroblasts |
| Fibroblasts. Fibroblasts provide a structural framework (stroma) for many tissues, and play a critical role in wound healing. They are the most common cells of connective tissue in animals. Wikipedia. |
| New promising therapy against systemic sclerosis. There are three leading actors in the genesis of the diseases. First, the fibroblasts, cells producing connective tissue of all apparatuses, which are the responsible of the production of the tissue- and skin-hardening proteins. Secondly, the endothelial cells, the ones coating the interior part of the vessels and that provoke very dangerous occlusions. Finally, the immune system cells, which are exactly the ones causing an excessive response, that provoke the autoimmune disease. Gianfranco Ferraccioli. EurekAlert! 06/14/10. (Also see: Endothelin cells) |
| Sticking it to Scleroderma: Potential Therapies Blocking Elevated Adhesive and Contractile Signaling. During repair of connective tissue, resting fibroblasts become `activated'; that is, they migrate into the wound where they synthesize and remodel new extracellular matrix. Leask, Andrew. (IngentaConnect) Current Enzyme Inhibition, Vol. 6, No. 2, July 2010. Pp. 97-104(8). (Also see: Wound Healing) |
| Dihydrosphingosine-1 phosphate has a potent anti-fibrotic effect in Scleroderma fibroblasts via normalization of PTEN levels. Our findings demonstrate that PTEN deficiency is a critical determinant of the pro-fibrotic phenotype of SSc fibroblasts. The anti-fibrotic effect of dhS1P is mediated through normalization of PTEN expression levels, suggesting that dhS1P or its derivatives may be effective as therapeutic anti-fibrotic agents. Bu S. Arthritis Rheum. 2010 Mar 22. (PubMed). |
| Differential Dynamic Properties of Scleroderma Fibroblasts in Response to Perturbation of Environmental Stimuli. We find that TGF-β pathway under perturbation of silica shows significant differences in dynamic properties between normal and scleroderma fibroblasts. Our findings may open a new avenue in exploring the functions of cells and mechanism operative in disease development. Momiao Xiong. PloS ONE (2008) 3(2):e1693. (Also see: Causes of Scleroderma: Silica) |
| When healing turns to scarring: Research reveals why it happens and how to stop it. During tissue repair, specialized cells called myofibroblasts migrate to the wound where they generate the adhesive and tensile forces required for wound closure. Normally, these myofibroblasts then disappear from the wound. But if they persist and continue to make connective tissue, it can become too thick, preventing the organ from functioning properly. EurekAlert! 09/18/08. (Also see: Causes of Scleroderma: Endothelin) |
| Genetics and Scleroderma |
| Causes of Scleroderma: Genetics includes information on DNA, Familial CRST with Sicca Syndrome, Familial Progressive Systemic Sclerosis (FPSS), studies of twins, Choctaw genetic study, and human genome project. ISN. |
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| Gluten Sensitivity |
| Celiac Disease and Gluten Sensitivity. Gluten sensitivity is a known cause of dozens of autoimmune diseases, including Hashimoto's thyroiditis, Sjogren's syndrome, and scleroderma. ISN. |
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| Hormones and Chromosomes |
| Hormones and Chromosomes have been found to attribute to the development of autoimmune diseases. This may explain why women are more susceptible to autoimmune diseases than men. ISN. |
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| Infection |
| Causes of Scleroderma: Infections Researchers have long suspected an infection component may be involved as the trigger of some cases of scleroderma and there is an ongoing study about persistent infection as a possible cause of scleroderma. ISN. |
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| Interleukins |
| Causes of Scleroderma: Interleukins Interleukin-10 gene is associated with scleroderma; interleukin-1 may upregulate scleroderma fibroblasts; interleukin-13 is associated with localized scleroderma. ISN. |
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| Mercury Exposure (Dental Amalgam) |
| Causes of Scleroderma: Mercury Exposure (Dental Amalgam) covers recent research indicating that there may be a link between mercury exposure and autoimmune diseases. ISN. |
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| Molecular Defect - TGF Dysregulation |
| Causes of Scleroderma: Molecular Defect in TGFbeta/SMAD may play a role in the development of scleroderma fibrosis. ISN. |
| Natural Killer Cells |
| Important Control Mechanism Behind Autoimmune Diseases Discovered. Patients with SLE (Systemic lupus erythematosus) and other autoimmune diseases have lower levels of so-called NKT (Natural Killer T) cells. "We've demonstrated that NKT cells can regulate how B cells become activated against healthy tissue, and that a lack of NKT cells results in greater misguided B cell activation," says Dr Karlsson. "So now we can mechanically link the NKT cell defect in patients to the disease." Medical News Today. May 5 2010. (Also see: Causes of Autoimmunity) |
| Natural killer (NK) cells in atopic and autoimmune diseases of the skin. NK cells are best known for their ability to recognize and kill tumor cells and virally infected cells and for their ability to produce large amounts of some cytokines, such as IFN-γ. We believe that there is solid evidence that NK cells actively participate in a number of diseases that have not been traditionally linked to this type of lymphocyte, including atopic and autoimmune diseases of the skin. D.V. Bubnoff, MD. The Journal of Allergy and Clinical Immunology. Volume 125, Issue 1, Pages 60-68 (January 2010). (Also see: Causes of Autoimmunity) |
| Association of killer cell immunoglobulin -like receptors (KIRs) with primary Sjögren's syndrome (SS). Autologous KIR–ligand interaction may be a contributory factor to predisposition for SS. D. Lowe. Rheumatology. January 30, 2009. (Also see: Sjögren's) |
| Natural Immune-control System May Aid Treatment Of Autoimmune Disease And Tissue Rejection. "Our findings suggest that it is possible to use antibodies to trigger the body's own mechanism for suppressing the immune response," Cantor remarks. "The results serve as a proof of principle that this approach can be applied to the treatment of conditions characterized by an excessive or unwanted immune response." Science Daily. 05/17/07. |
| Oxidative Stress, Lipid Peroxidation |
| Exercise in systemic sclerosis (SSc) intensifies systemic inflammation and oxidative stress. Although exercise capacity is impaired in patients with SSc, physical activity intensifies the already increased basal levels of systemic inflammation and oxidative stress. These data support the concept of a role for systemic inflammation and oxidative stress in the ongoing systemic effects of SSc. H Harðardóttir. (PubMed) Scand J Rheumatol. 2010;39(1):63-70. |
| Vascular Inflammation in Obesity and Sleep Apnea. Untreated obstructive sleep apnea rather than obesity is a major determinant of vascular endothelial dysfunction, inflammation, and elevated oxidative stress in obese patients. Sanja Jelic MD. Circulation. February 16, 2010 (Also see: Sleep Apnea) |
| Abnormal exhaled ethane concentrations in scleroderma. Scleroderma is a chronic multisystem autoimmune disease in which oxidative stress is suspected to play a role in the pathophysiology. It was postulated that patients with scleroderma would have abnormally high breath ethane concentrations, a volatile product of free-radical-mediated lipid peroxidation. PubMed. Biomarkers. 2006 Jan-Feb;11(1):70-84. |
| Antioxidant defense capacity in scleroderma patients. Lower plasma total antioxidant activity and plasma antioxidant gap in scleroderma patients show that plasma antioxidant defense is deficient in scleroderma patients. As previous studies on this issue are controversial, the decreased erythrocyte superoxide dismutase activity found in the patients in this study needs further investigation. Sfrent-Cornateanu R. PubMed. Clin Chem Lab Med. 2008;46(6):836-41. (Also see: Alternative Treatments) |
| Platelet Aggregation |
| Platelet aggregation is the clumping of platelets together, using fibrin (a protein involved in the clotting of blood) as the connecting agent. Widipedia. |
| A Polymorphism In The Human Serotonin 5-HT2A Receptor Gene May Protect Against Systemic Sclerosis By Reducing Platelet Aggregation. Platelet aggregation may contribute to the pathogenesis of systemic sclerosis: following activation platelets release significant amounts of serotonin which promotes vasoconstriction, fibrosis and further enhances aggregation. L, Beretta. Arthritis Research & Therapy 2008, 10:R103. |
| Proteins |
| Inflammation's trigger finger. A molecule found in nearly all cells plays a vital role in kick-starting the production of key biological molecules involved in inflammation. The finding may lead to new strategies for blocking the devastating inflammation that lies at the heart of autoimmune disorders such as multiple sclerosis, arthritis, lupus as well as some cancers. innovations report. Salk Institute 07/20/04. |
| Radiation |
| Radiation and Scleroderma. There is an increased rate of cancer among scleroderma patients. Furthermore, scleroderma patients have an increased sensitivity to radiation treatments. In addition, radiation can cause scleroderma including Radiation Port Scleroderma. ISN. |
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| Serum TIMP-2 |
| Serum Levels of Tissue Inhibitors of Metalloproteinase 2 in Patients With Systemic Sclerosis (SSc) With Duration More Than 2 Years: Correlation With Cardiac and Pulmonary Abnormalities. This study confirms the probable role of TIMP-2 in inducing fibrosis in the course of SSc, and suggests a possible role of TIMP-2 in the development of pulmonary involvement in dSSc patients, and cardiac lesions in lSSc patients, with disease duration equal to or more than 2 years. Amira Shahin. (PubMed) Mediators Inflamm. 2006; 2006(6): 38458. |
| Serum sCD40 |
| Increased Serum Soluble CD40 Levels in Patients with Systemic Sclerosis. Elevated serum sCD40 levels were associated with lcSSc. These results suggest that the blockade of CD40/CD40 ligand interaction could be a potential therapeutic strategy in SSc. J Rheumatol 2007 February;34:353–8. (Also see: Limited Scleroderma) |
| Silica |
| Causes of Scleroderma: Silica. Silica exposure can cause autoimmune diseases such as lupus, scleroderma, and vasculitis. It can also cause silicosis, kidney disease, lung cancer, tuberculosis, and other airways diseases. Environmental exposure to silica can occur in workers and bystanders in many industries, including agriculture, construction, and pottery. ISN. (Also see: Causes of Scleroderma: Silicone Breast Implants) |
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| Sleep Disorders |
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| Stress |
| Stress can cause hormonal and cellular changes in our bodies which can lead to a variety of medical problems. Chronic stress is thought to be a trigger for the development or exacerbation of autoimmune diseases. ISN. |
| Tissue Kallikrein (t-kallikrein) |
| Increased circulating levels of tissue kallikrein in systemic sclerosis correlate with microvascular involvement. T-kallikrein levels are increased in patients with SSc, particularly in lSSc, and are associated with early and active capillaroscopic patterns. T-kallikrein may play a part in SSc microvascular changes. PubMed. Ann Rheum Dis. 2005 Mar;64(3):382-7. (Also see: Raynaud's) |
| Thyroid |
| Thyroid Disease. It is common for people to develop thyroid diseases, such as hyperthyroidism (hyper means "too much") and hypothyroidism (hypo means "too little.) The two main types of autoimmune thyroid disease fall into hyperthyroidism (Grave's disease), and hypothyroidism (Hashimoto's thyroiditis). Often thyroid disease occurs by itself. Occasionally it is also associated with other autoimmune diseases, such as type 1 diabetes, systemic scleroderma, and vitiligo, just to name a few. ISN. |
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| Vitamin D Deficiency |
| Vitamin D 's major biological function is to maintain normal blood levels of calcium and phosphorus. Recent studies have demonstrated that individuals with low blood levels of vitamin D are at a higher risk of developing autoimmune diseases. ISN. |
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| Footnotes |
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