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Sjögren's syndrome

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:1136
Name:Sjögren's syndrome
Associated with:2 targets
1 immuno-relevant target
9 immuno-relevant ligands
Synonyms
Sicca syndrome | Sjögren-Gougerot syndrome
Description
Sjögren's syndrome is a chronic autoimmune disorder characterized by the triad of dry eyes (keratoconjunctiva sicca), sensation of oral dryness (xerostomia) and/or swelling of the salivary glands secondary to lymphocytic infiltration and destruction of the exocrine glands.
Database Links
Orphanet: ORPHA378

Targets

GtoPdb Disease Summaries - Targets

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

Where available, information is display on the 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 appropriate 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
CXCR5
References:  6
Ligand interactions: 
Ligand Comments
CXCL13
Serum CXCL13 is elevated in patients with SS, compared to healthy controls. Expression of CXCL13 in ectopic lymphoid-like follicles in salivary glands ...
BAFF receptor
Comments:  Molecular target for SS- see NCT02962895 which is designed to evaluate clinical efficacy of anti-BAFF-R mAb VAY736 in SS patients.

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
leniolisib
Immuno Disease Comments: Completed Phase 2 clinical trial NCT02775916 as monotherapy for primary SS.
Clinical Use: Leniolisib (CDZ173) was evaluated in clinical trial in patients with genetically activated PI3Kδ (i.e. patients with APDS/PASLI; see Phase 2/3 trial NCT02435173). Positive results from NCT02435173 are reported by Rao et al. (2017) [10], showing that leniolisib was well tolerated and improved laboratory and clinical parameters in APDS patients. The FDA approved leniolisib as a treatment for APDS in March 2023 [4]. | View clinical data
Bioactivity Comments: Data are presented for Example 67 in patent WO2012004299 [3]. | View biological activity
seletalisib
Immuno Disease Comments: Phase 2 clinical candidate for primary SS, but trial NCT02610543 was terminated as they struggled to recruit patients.
Clinical Use: First-in-human results were reported by Helmer et al. (2017) [7]. This article reports data from clinical trials NCT02303509 (safety and tolerability in healthy and psoriatic subjects) and NCT02207595 (safety and tolerability in healthy subjects only). A proof of concept Phase 2 trial in patients with primary Sjögren's syndrome has been terminated due to difficulty in enrolling suitable patient numbers (NCT02610543). | View clinical data
CFZ533
Immuno Disease Comments: Phase 2 clinical candidate for primary Sjögren's syndrome- see NCT02291029
Clinical Use: CFZ533 is being evaluated in clinical trials as a therapy for some autoimmune conditions and for preventing/reducing solid organ transplant rejection. Click here to link to ClinicalTrials.gov's full list of CFZ533 trials. | View clinical data
Bioactivity Comments: CFZ533 (mAb1) shows no agonist activity in an in vitro assay using isolated human PBMCs, blocks -mediated PBMC proliferation (IC50 58 ng/ml), inhibits CD40L-mediated TNF-α release from human monocyte derived dendritic cells (IC50 40 ng/ml), and has ADCC activity of < 1% (measuring specific lysis) [8]. | View biological activity
belimumab
Immuno Disease Comments: In clinical trial for this indication- see NCT02631538, in combination with rituximab.
Clinical Use: Approved as an adjunctive treatment for systematic lupus erythematosus (SLE) [9]. The original formulation of belimumab was administered intravenously. In July 2017, a new self-injectable subcutaneous formulation of belimumab for the treatment of adult patients with active, autoantibody‑positive SLE was FDA approved, which allows patients to self-administer their medicine at home rather than going to medical facilities to receive their i.v. infusions.
Additional indications being evaluated with belimumab include vasculitis (Phase 3), and myaesthenia gravis and transplant rejection (both Phase 2). | View clinical data
petesicatib
Immuno Disease Comments: Completed Phase 2 evaluation in SS- see NCT02701985.
Clinical Use: (RO5459072 or RG7625) has completed Phase 2 clinical evaluation in Sjögren's syndrome (NCT02701985) and Phase 1 in celiac disease (NCT02679014), but there are no active clinical trials registered with ClinicalTrials.gov. | View clinical data
Bioactivity Comments: Petesicatib (RO5459072) is selective for cathepsin S compared to other cathepsin isozymes examined [12]. | View biological activity
parsaclisib
Immuno Disease Comments: Phase 2 clinical lead for SS- see NCT03627065
Clinical Use: Parsaclisib (INCB50465) has advanced to Phase 2 clinical trial. It is being evaluated in multiple studies looking at its efficacy in various lymphomas and B cell malignancies, and in Sjögren's syndrome and autoimmune hemolytic anemia. NCT04142554 will evaluate parsaclisib in patients with triple negative or HER2+ breast cancers. Click here to link to ClinicalTrials.gov's full list of INCB50465 trials. | View clinical data
CXCL13 2,5,11
Immuno Disease Comments: Serum CXCL13 is elevated in patients with SS, compared to healthy controls. Expression of CXCL13 in ectopic lymphoid-like follicles in salivary glands of SS patients has been suggested as a potential disease marker. CXCL13 levels are reduced by blockade of lymphotoxinβ receptor in the NOD mouse model of SS.
tibulizumab
Immuno Disease Comments: Phase 1 trial NCT02614716 in SS has been completed.
Clinical Use: Tibulizumab (LY3090106) is a Phase 1 clinical candidate for Sjögren's syndrome and rheumatoid arthritis. Click here to link to ClinicalTrials.gov's full list of tibulizumab trials. | View clinical data
Bioactivity Comments: Tibulizumab binds the heterodimer with a Kd of ~90 pM [1]. It binds both soluble and membrane-bound BAFF. | View biological activity
RSLV-132
Immuno Disease Comments: RSLV-132 has progressed to Phase 2 clinical evaluation in SS patients- see NCT02660944
Clinical Use: RSLV-132 has been advanced to clinical evaluations in autoinflammatory conditions. It has been entered into a clinical study to determine efficacy in patients with long-COVID. | View clinical data

References

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1. Allan B, Benschop RJ, Lu J. (2013) Anti-baff-anti-il-17 bispecific antibodies. Patent number: WO2013158577A1. Assignee: Eli Lilly. Priority date: 20/04/2012. Publication date: 24/10/2013.

2. Barone F, Bombardieri M, Manzo A, Blades MC, Morgan PR, Challacombe SJ, Valesini G, Pitzalis C. (2005) Association of CXCL13 and CCL21 expression with the progressive organization of lymphoid-like structures in Sjögren's syndrome. Arthritis Rheum, 52 (6): 1773-84. [PMID:15934082]

3. Cooke NG, Fernandes GDSP, Graveleau N, Hebach C, Hogenauer K, Hollingworth G, Smith AB, Soldermann N, Stowasser F, Strang R et al.. (2012) Tetrahydro-pyrido-pyrimidine derivatives. Patent number: WO2012004299. Assignee: Novartis Ag. Priority date: 06/07/2010. Publication date: 12/01/2012.

4. Duggan S, Al-Salama ZT. (2023) Leniolisib: First Approval. Drugs, 83 (10): 943-948. [PMID:37256490]

5. Fava RA, Kennedy SM, Wood SG, Bolstad AI, Bienkowska J, Papandile A, Kelly JA, Mavragani CP, Gatumu M, Skarstein K et al.. (2011) Lymphotoxin-beta receptor blockade reduces CXCL13 in lacrimal glands and improves corneal integrity in the NOD model of Sjögren's syndrome. Arthritis Res Ther, 13 (6): R182. [PMID:22044682]

6. Hansen A, Lipsky PE, Dörner T. (2007) B cells in Sjögren's syndrome: indications for disturbed selection and differentiation in ectopic lymphoid tissue. Arthritis Res Ther, 9 (4): 218. [PMID:17697366]

7. Helmer E, Watling M, Jones E, Tytgat D, Jones M, Allen R, Payne A, Koch A, Healy E. (2017) First-in-human studies of seletalisib, an orally bioavailable small-molecule PI3Kδ inhibitor for the treatment of immune and inflammatory diseases. Eur J Clin Pharmacol, 73 (5): 581-591. [PMID:28160012]

8. Heusser C, Rush J, Vincent K. (2012) Silent fc variants of anti-cd40 antibodies. Patent number: WO2012065950. Assignee: Novartis Ag. Priority date: 15/11/2010. Publication date: 24/05/2012.

9. Lutalo PM, D'Cruz DP. (2014) Update on belimumab for the management of systemic lupus erythematosus. Expert Opin Biol Ther, 14 (11): 1701-8. [PMID:25303323]

10. Rao VK, Webster S, Dalm VASH, Šedivá A, van Hagen PM, Holland S, Rosenzweig SD, Christ AD, Sloth B, Cabanski M et al.. (2017) Effective "activated PI3Kδ syndrome"-targeted therapy with the PI3Kδ inhibitor leniolisib. Blood, 130 (21): 2307-2316. [PMID:28972011]

11. Salomonsson S, Jonsson MV, Skarstein K, Brokstad KA, Hjelmström P, Wahren-Herlenius M, Jonsson R. (2003) Cellular basis of ectopic germinal center formation and autoantibody production in the target organ of patients with Sjögren's syndrome. Arthritis Rheum, 48 (11): 3187-201. [PMID:14613282]

12. Tato M, Kumar SV, Liu Y, Mulay SR, Moll S, Popper B, Eberhard JN, Thomasova D, Rufer AC, Gruner S et al.. (2017) Cathepsin S inhibition combines control of systemic and peripheral pathomechanisms of autoimmune tissue injury. Sci Rep, 7 (1): 2775. [PMID:28584258]