| Causes of Scleroderma (MAIN MENU) | | | |
| Molecular Defect |
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| Mitochondrial Antibodies |
| Mitochondrial Autoantibodies. Concentrations of mitochondrial autoantibodies (MA), which are found in ~95% of patients with primary biliary cirrhosis (PBC), do not correlate with disease stage and prognosis, but are now known to play an important role in the immunopathogenesis of PBC. Approximately 3% of patients with PBC have scleroderma, usually of the CREST syndrome variety. Specialty Laboratories. (Also see: Types of Scleroderma and Liver Involvement ) |
| United Mitochondrial Disease Foundation. Mitochondrial diseases result from failures of the mitochondria, specialized compartments present in every cell of the body except red blood cells. Mitochondria are responsible for creating more than 90% of the energy needed by the body to sustain life and support growth. When they fail, less and less energy is generated within the cell. United Mitochondrial Disease Foundation. |
| Human enteric neuropathies: morphology and molecular pathology. The aim of this study is to review current understanding of the molecular and morphological pathology of the enteric neuropathies affecting motor function of the human gastrointestinal tract. PubMed. Neurogastroenterol Motil. 2004 Oct;16(5):515-31. (Also see: GI Involvement ) |
| Patterns of autoimmunity in primary biliary cirrhosis patients and their families: a population-based cohort study. Primary biliary cirrhosis (PBC) is a chronic liver disease characterized by damage to, and destruction of, the biliary epithelial cells lining small intra-hepatic bile ducts.1 PBC exhibits a number of autoimmune features, including the almost universal presence of auto-antibodies reactive with highly conserved mitochondrial antigens (anti-mitochondrial antibodies, AMA). Q J Med 2004; 97: 397-406. (Also see: Liver Involvement ) |
| TGF Dysregulations |
| Some researchers suspect that a molecular defect in TGFbeta/SMAD may play a role in the development of scleroderma fibrosis. |
| Skin involvement in scleroderma--where histological and clinical scores meet. The histological extent of skin fibrosis correlates closely with the mRSS. Both parameters appeared to regress after HSCT (haematopoietic stem cell transplantation). The extent of TGF-beta signalling activation in SSc skin fibroblasts appears to parallel the severity of disease. PubMed. Rheumatology (Oxford). 2007 Jan 25. (Also see: Skin Fibrosis ) |
| Urticarial vasculitis appearing in the progression of systemic sclerosis (SSc). We demonstrate that, in the present case, mast cells might be involved in both courses of urticarial vasculitis and SSc as a common factor. PubMed. J Dermatol. 2006 Nov;33(11):792-7. (Also see: Vasculitis, Skin Fibrosis, and Limited Scleroderma ) |
| New Treatment Hope For Systemic Sclerosis (SSc). On experimental fibroblast cultures from SSc patients, imatinib mesylate (a small growth factor inhibiting molecule) strongly reduced the synthesis of EMC proteins, the number of myofibroblasts, and the thickness of skin, almost back to levels observed in the healthy control groups. Science Daily. 12/29/06. (Also see: Treatments and Causes of Scleroderma: Cytokines ) |
| A clue for telangiectasis in systemic sclerosis: elevated serum soluble endoglin levels in patients with the limited cutaneous form of the disease. Patients with elevated sEndoglin levels had telangiectasia more frequently than those with normal sEndoglin levels. PubMed. Dermatology. 2006;213(2):88-92. (Also see: Telangiectasia, Pulmonary Hypertension, and Limited Scleroderma ) |
| Scar wars: is TGFbeta the phantom menace in scleroderma (SSc)? Recently, the signaling pathways through which TGFbeta activates a fibrotic program have been elucidated and several possible points for anti-fibrotic drug intervention in SSc have emerged. PubMed. Arthritis Res Ther. 2006 Jun 9;8(4):213. |
| Stimulatory Autoantibodies to the PDGF Receptor in Systemic Sclerosis. Stimulatory autoantibodies against PDGFR (platelet-derived growth factor) appear to be a specific hallmark of scleroderma. Their biologic activity on fibroblasts strongly suggests that they have a causal role in the pathogenesis of the disease.The New England Journal of Medicine. Volume 354:2667-2676:25. 06/22/06. |
| Nodular scleroderma: increased expression of connective tissue growth factor. Nodular scleroderma is a fibrosing reaction, presenting well-defined, firm, raised nodules, which resembles keloid. Our data showed increased expression of CTGF in the sclerotic fibroblasts of nodular scleroderma, suggesting that CTGF plays an important role in its pathogenesis. PubMed. Dermatology. 2005;211(3):218-23. (Also see: Keloid, Nodular, or Keloid-Like Morphea Scleroderma) |
| Scleroderma, fibroblasts, signaling, and excessive extracellular matrix (ECM). ECM deposition in the skin, lung, and other organs is a hallmark of systemic sclerosis (SSc). Increasing evidence suggests that various cytokines such as transforming growth factor (TGF)-beta and their signaling pathways are key mediators of tissue fibrosis as a consequence of ECM accumulation in the pathogenesis of fibrosis such as SSc. PubMed. Curr Rheumatol Rep. 2005 Apr;7(2):156-62. |
