loading...| Preferred Name | Graves Ophthalmopathy | |
| Synonyms |
PathwayType: signaling Organ: eye Description: Graves ophthalmopathy (GO) is an autoimmune inflammation of orbits that progresses in Graves disease (GD). Pathway is built manually using published studies. Pathway_Author: A. Nesterova ORCID:0000-0002-9448-8101 Link: https://mammal-profservices.pathwaystudio.com/app/sd?urn=urn:agi-pathway:uuid-dcc6e065-6eac-48ea-9a96-9751e23f6200 Organ_System: sensory system NodeType: Pathway Notes: Headnote: Graves ophthalmopathy (GO) is an autoimmune inflammation of orbits that progresses into Graves disease (GD). Graves disease (GD) is characterized by hyperthyroidism, particular ophthalmopathy, and pretibial myxedema. The disease is caused by an autoimmune response to thyroid antigens. Signaling description: In GO, orbit tissues are infiltrated with lymphocytes and macrophages, while muscle and adipose cells increase in size. Hyaluronic acid is accumulated in the extracellular space. As a result, an inflammatory response is initiated which increases ocular pressure causing pain. GO may occur before, concurrently with, or after the onset of Graves hyperthyroidism. While some degree of ocular involvement such as increased eye muscle thickness can be detected by sensitive imaging techniques including magnetic resonance or computed tomography in almost all patients with GD, clinically apparent ophthalmopathy occurs in 25-50% of patients with GD. A severe form occurs in 3-5% of patients. The immune reaction against TSHR in fibroblast cell membranes leads to fibroblast stimulation and an excess production of collagen and glycosaminoglycans. In addition, several other secondary autoantigens have been detected in affected extraocular muscles such as the flavoprotein subunit of mitochondrial succinate dehydrogenase, G2s, sarcalumenin, and calsequestrin. Antibodies against calsequestrin and collagen XIII have been shown to be very specific and sensitive diagnostic markers for GO. The exact role of genetic factors in the development of GO is unknown, although several susceptibility loci have been proposed. Outcome effects: The presence of autoantibodies for TSHR may activate this receptor on the surface of orbital fibroblasts. TSHR activation causes cell proliferation, secondary activation of immune system cells, and an increase in the expression of enzymes that synthesize hyaluronic acid (HAS1 and HAS2). Additionally, IGF1R exerts similar action and is also overexpressed in patients with GO. Hyaluronic acid synthesis is increased by TGFB1, IL1B, IL1A, IFNG, and IL4 cytokines which are produced by T-cells. The altered function of adhesion molecules such as THY1 and ICAM1 may also participate in the progression of the disorder. Finally, a high level of IL6 may be observed in GO. IL6 can activate adipocyte differentiation, through STAT3 signaling. Highlighted proteins: Proteins with increased expression or activity are highlighted in red. CellType: fibroblast PMID: 17521325 PMID: 16365140 Source: Diseases |
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| ID |
urn:agi-pathway:uuid-dcc6e065-6eac-48ea-9a96-9751e23f6200 |
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| database_cross_reference |
PS:PathwayType PS:Description PS:Pathway_Author PS:Link PS:CellType PS:Organ_System PS:PMID PS:NodeType PS:Notes PS:Organ PS:Source |
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| has_exact_synonym |
PathwayType: signaling Organ: eye Description: Graves ophthalmopathy (GO) is an autoimmune inflammation of orbits that progresses in Graves disease (GD). Pathway is built manually using published studies. Pathway_Author: A. Nesterova ORCID:0000-0002-9448-8101 Organ_System: sensory system NodeType: Pathway Notes: Headnote: Graves ophthalmopathy (GO) is an autoimmune inflammation of orbits that progresses into Graves disease (GD). Graves disease (GD) is characterized by hyperthyroidism, particular ophthalmopathy, and pretibial myxedema. The disease is caused by an autoimmune response to thyroid antigens. Signaling description: In GO, orbit tissues are infiltrated with lymphocytes and macrophages, while muscle and adipose cells increase in size. Hyaluronic acid is accumulated in the extracellular space. As a result, an inflammatory response is initiated which increases ocular pressure causing pain. GO may occur before, concurrently with, or after the onset of Graves hyperthyroidism. While some degree of ocular involvement such as increased eye muscle thickness can be detected by sensitive imaging techniques including magnetic resonance or computed tomography in almost all patients with GD, clinically apparent ophthalmopathy occurs in 25-50% of patients with GD. A severe form occurs in 3-5% of patients. The immune reaction against TSHR in fibroblast cell membranes leads to fibroblast stimulation and an excess production of collagen and glycosaminoglycans. In addition, several other secondary autoantigens have been detected in affected extraocular muscles such as the flavoprotein subunit of mitochondrial succinate dehydrogenase, G2s, sarcalumenin, and calsequestrin. Antibodies against calsequestrin and collagen XIII have been shown to be very specific and sensitive diagnostic markers for GO. The exact role of genetic factors in the development of GO is unknown, although several susceptibility loci have been proposed. Outcome effects: The presence of autoantibodies for TSHR may activate this receptor on the surface of orbital fibroblasts. TSHR activation causes cell proliferation, secondary activation of immune system cells, and an increase in the expression of enzymes that synthesize hyaluronic acid (HAS1 and HAS2). Additionally, IGF1R exerts similar action and is also overexpressed in patients with GO. Hyaluronic acid synthesis is increased by TGFB1, IL1B, IL1A, IFNG, and IL4 cytokines which are produced by T-cells. The altered function of adhesion molecules such as THY1 and ICAM1 may also participate in the progression of the disorder. Finally, a high level of IL6 may be observed in GO. IL6 can activate adipocyte differentiation, through STAT3 signaling. Highlighted proteins: Proteins with increased expression or activity are highlighted in red. CellType: fibroblast PMID: 17521325 PMID: 16365140 Source: Diseases |
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| id |
urn:agi-pathway:uuid-dcc6e065-6eac-48ea-9a96-9751e23f6200 |
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| label |
Graves Ophthalmopathy |
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| notation |
uuid-dcc6e065-6eac-48ea-9a96-9751e23f6200 |
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| prefLabel |
Graves Ophthalmopathy |
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| treeView |
urn:agi-folder:hyperthyroidism urn:agi-folder:g urn:agi-folder:sensory_system |
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| subClassOf |
urn:agi-folder:hyperthyroidism urn:agi-folder:g urn:agi-folder:sensory_system |