Scleroderma Symptoms Causes

Molecular Defect

Mitochondrial Antibodies

Mitochondrial Antibodies occur in about 95% of people who have primary biliary cirrhosis (PBC), but only 3% of people who have PBC have systemic scleroderma. (Also see What is Scleroderma? and Types of Scleroderma)

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.

Pyruvate kinase M2 and the mitochondrial ATPase Inhibitory Factor 1 provide novel biomarkers of dermatomyositis: a metabolic link to oncogenesis. Reverse phase protein microarrays identified the glycolysis promoting PKM2 and IF1 proteins as specific biomarkers of dermatomyositis, providing a biochemical link of this inflammatory myopathies with oncogenesis. PubMed, J Transl Med, 2017 Feb 10;15(1):29.

Low Cytochrome Oxidase 1 Links Mitochondrial Dysfunction to Atherosclerosis in Mice and Pigs. Low mitochondria–encoded cytochrome oxidase 1 is related to mitochondrial dysfunction, oxidative stress and atherosclerosis and plaque complexity. PubMed, PLoS One. 2017 Jan 25;12(1):e0170307.

The Fingerprint of Antimitochondrial Antibodies and the Etiology of Primary Biliary Cholangitis (PBC). A molecular understanding of the conformation of xenobiotic modified PDC-E2 is critical for understanding xenobiotic modification and loss of tolerance in PBC with widespread implications for a role of environmental chemicals in the induction of autoimmunity. PubMed, Hepatology, 01/18/2017. (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.

Transforming growth factor-ß plasma levels and its role in amyotrophic lateral sclerosis (ALS). Our preliminary results support the hypothesis that TGF-ß3 levels can be a marker disease severity ALS. PubMed, Med Hypotheses, 2020 Feb 14;139:109632.

Evolving insights into the cellular and molecular pathogenesis of fibrosis in systemic sclerosis. This article looks to identify clinical applications where this new molecular knowledge may allow for targeted treatment and personalized medicine approaches. PubMed, Transl Res, 2019 Jul;209:77-89. (Also see Skin Fibrosis)

Transforming growth factor-ß increases interleukin-13 synthesis via GATA-3 transcription factor in T-lymphocytes from patients with systemic sclerosis (SSc). These results demonstrate that TGF-ß upregulates IL-13 synthesis through GATA-3 expression in the T lymphocytes of patients with SSc, confirming that the GATA-3 transcription factor can be regarded as a novel therapeutic target in patients with SSc. PubMed, Arthritis Res Ther. (Also see Interleukins)

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