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Temporal arteritis

GtoPdb Disease Summaries

This section gives an overview of the disease, and where available shows the following:

  • Synonyms: Shows known synonyms for the disease.
  • Description: Gives a basic description/definition of the disease.
  • Database Link: External links to the same disease at the Disease Ontology, OMIM or Orphanet sites.
  • Immunopharmacology comments: General comments about the target's role in immunopharmacology, provided by GtoImmuPdb curators.
  • Associated with: Counts are displayed for the total targets the disease is associated with in GtoPdb. The counts of targets and ligands of immunological relevance associated to the disease are also shown.

More information can be found in the help pages.

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Disease ID:1039
Name:Temporal arteritis
Associated with:1 target
2 immuno-relevant ligands
Synonyms
Giant cell arteritis
Database Links
Disease Ontology: DOID:13375
OMIM: 187360
Orphanet: ORPHA397

Targets

GtoPdb Disease Summaries - Targets

Click on the target name to link to its detailed view page

Where available, information is display on role of the target in the disease; drugs which target the disease and their therapeutic use and side-effects.

If there is mutation data curated in GtoPdb this is indicated, with a link back to the approriate section on the target detailed view page

Immuno ligand interactions - If available, a table of immuno-relevant ligands is shown. These ligands have been curated as having an association to the disease and possess interaction data with the target in GtoPdb. The approval status of the ligand is shown, along with curator comments and an indication of whether the target is considered the primary target of the ligand.

More information can be found in the help pages.

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Key to terms and symbols
NLRP1

Ligands

GtoPdb Disease Summaries - Ligands

Click ligand name to view ligand summary page

  • Approved: If the ligand is an approved drug this is indicated, along with approval bodies.
  • Immuno: Immuno icon indicates the ligand is immuno-relevant

Click the arrow in the final column to expand comments

  • Immuno Disease Comments: Curatorial comments specifically added as part of GtoImmuPdb. They give more information on the association between the ligand and disease in the context of immunopharmacology.
  • Clinical Use: General clinical comments relating to the ligand and may not necessarily be specific to the disease in question. With hyperlink to more details on the ligand summary pages.
  • Bioactivty Comments: Curatorial comments specifically about the compounds biological activity - with hyperlink to more details on the ligand summary pages.

More information can be found in the help pages.

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Key to terms and symbols Click ligand name to view ligand summary Click column headers to sort
Ligand References Clinical and Disease comments
tocilizumab
Immuno Disease Comments: Approved drug for temporal (giant cell) arteritis (May 2017).
Clinical Use: tocilizumab had been approved in Japan in 2005 as a treament for giant lymph node hyperplasia (Castleman's disease) [4], before being granted EMA and FDA approvals for use as a treatment for rheumatoid arthritis [3,6] and systemic and polyarticular juvenile idiopathic arthritis [8].
In May 2017 tocilizumab became the first FDA approved drug for the treatment of adults with giant cell arteritis.
Phase 3 clinical trials for immune conditions including ankylosing spondylitis, hand osteoarthritis, systemic sclerosis and primary Sjögren's syndrome (pSS) are ongoing. Tocilizumab was initally used off-label to manage severe or life-threatening cytokine release syndrome (CRS), which is a serious, and potentially life-threatening side effect of CAR T-cell therapy. In September 2017, the FDA extended tocilizumab approval to include treatment of CAR T-cell therapy-induced CRS. It was approved particularly to manage CRS in patients ≥2 years of age receiving tisagenlecleucel (Kymriah®,CTL019), the first CAR T-cell therapy approved for relapsed and refractory B-cell ALL. | View clinical data
Bioactivity Comments: Unfortunately, we have been unable to find publicly available data providing a binding affinity for this antibody at its molecular target. | View biological activity
sirukumab
Immuno Disease Comments: Phase 3 clinical candidate for temporal arteritis (giant cell arteritis)- see NCT02531633
Clinical Use: Phase 3 clinical trials assessing sirukumab for RA have been completed or are still ongoing (Oct 2017). Click here to link to ClinicalTrials.gov's listing of Phase 3 sirukumab trials. Other trials are collecting data in additional inflammatory conditions including lupus nephritis [7], cutaneous lupus erythematosus, systemic lupus erythematosus and giant cell arteritis.
Research is beginning to indicate that the disease pathophysiology of depression may have an immune component [1-2,5], and reviewed in [9]. In particular, IL-6 has been identified as a susceptibility gene for major depressive disorder (MDD), with the promoter polymorphism rs1800797 showing a marginally significant correlation with cortical IL-6 expression [10]. This and other work (including [5]) has led to clinical trial of sirukumab as an adjunct to conventional antidepressant therapy in patients with MDD (see Phase 3 trial NCT02473289). | View clinical data

References

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1. Du Preez A, Leveson J, Zunszain PA, Pariante CM. (2016) Inflammatory insults and mental health consequences: does timing matter when it comes to depression?. Psychol Med, 46 (10): 2041-57. [PMID:27181594]

2. Hepgul N, Cattaneo A, Agarwal K, Baraldi S, Borsini A, Bufalino C, Forton DM, Mondelli V, Nikkheslat N, Lopizzo N et al.. (2016) Transcriptomics in Interferon-α-Treated Patients Identifies Inflammation-, Neuroplasticity- and Oxidative Stress-Related Signatures as Predictors and Correlates of Depression. Neuropsychopharmacology, 41 (10): 2502-11. [PMID:27067128]

3. Maini RN, Taylor PC, Szechinski J, Pavelka K, Bröll J, Balint G, Emery P, Raemen F, Petersen J, Smolen J et al.. (2006) Double-blind randomized controlled clinical trial of the interleukin-6 receptor antagonist, tocilizumab, in European patients with rheumatoid arthritis who had an incomplete response to methotrexate. Arthritis Rheum., 54 (9): 2817-29. [PMID:16947782]

4. Matsuyama M, Suzuki T, Tsuboi H, Ito S, Mamura M, Goto D, Matsumoto I, Tsutsumi A, Sumida T. (2007) Anti-interleukin-6 receptor antibody (tocilizumab) treatment of multicentric Castleman's disease. Intern. Med., 46 (11): 771-4. [PMID:17541233]

5. Money KM, Olah Z, Korade Z, Garbett KA, Shelton RC, Mirnics K. (2016) An altered peripheral IL6 response in major depressive disorder. Neurobiol. Dis., 89: 46-54. [PMID:26804030]

6. Ohsugi Y, Kishimoto T. (2008) The recombinant humanized anti-IL-6 receptor antibody tocilizumab, an innovative drug for the treatment of rheumatoid arthritis. Expert Opin Biol Ther, 8 (5): 669-81. [PMID:18407769]

7. Rovin BH, van Vollenhoven RF, Aranow C, Wagner C, Gordon R, Zhuang Y, Belkowski S, Hsu B. (2016) A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Treatment With Sirukumab (CNTO 136) in Patients With Active Lupus Nephritis. Arthritis Rheumatol, 68 (9): 2174-83. [PMID:27110697]

8. Yokota S, Miyamae T, Imagawa T, Katakura S, Kurosawa R, Mori M. (2005) Clinical study of tocilizumab in children with systemic-onset juvenile idiopathic arthritis. Clin Rev Allergy Immunol, 28 (3): 231-8. [PMID:16129907]

9. Young JJ, Bruno D, Pomara N. (2014) A review of the relationship between proinflammatory cytokines and major depressive disorder. J Affect Disord, 169: 15-20. [PMID:25128861]

10. Zhang C, Wu Z, Zhao G, Wang F, Fang Y. (2016) Identification of IL6 as a susceptibility gene for major depressive disorder. Sci Rep, 6: 31264. [PMID:27502736]