ArticleArthritis research & therapy2019
Differential effects of specific cathepsin S inhibition in biocompartments from patients with primary Sjögren syndrome.
Article in Arthritis research & therapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 31 citations in OpenAlex.
- A randomized, double-blind, placebo-controlled, parallel group study on the effects of a cathepsin S inhibitor in primary Sjögren's syndrome.Rheumatology (Oxford, England) · 2023Trial
- Immunological profiling and treatment patterns of primary Sjögren's disease patients with concomitant rheumatoid arthritis: a retrospective cohort study.Frontiers in immunology · 2026Article
- The pH-Dependent Specificity of Cathepsin S and Its Implications for Inflammatory Communications and Disease.Biochemistry · 2025Article
- Review
- Review
- A Review of the Tear Film Biomarkers Used to Diagnose Sjogren's Syndrome.International journal of molecular sciences · 2024Review
- Advances in Cathepsin S Inhibition: Challenges and Breakthroughs in Drug Development.Pathophysiology : the official journal of the International Society for Pathophysiology · 2024Review
- Antibody-peptide conjugates deliver covalent inhibitors blocking oncogenic cathepsins.Nature chemical biology · 2024Article
- Inhibition of Cathepsin S in Autoimmune CD25KO Mouse Improves Sjögren Disease-Like Lacrimal Gland Pathology.Investigative ophthalmology & visual science · 2024Article
- The Potential Utility of Salivary and Tear Proteomics to Discriminate Sjögren's Disease from Non-Sjögren's Sicca.International journal of molecular sciences · 2023Review
- Cell Cultures as a Versatile Tool in the Research and Treatment of Autoimmune Connective Tissue Diseases.Cells · 2023Review
- Cysteine Cathepsins as Therapeutic Targets in Immune Regulation and Immune Disorders.Biomedicines · 2023Review
- Evaluation of variable new antigen receptors (vNARs) as a novel cathepsin S (CTSS) targeting strategy.Frontiers in pharmacology · 2023Article
- The Future of Targeted Treatment of Primary Sjögren's Syndrome: A Focus on Extra-Glandular Pathology.International journal of molecular sciences · 2022Review
- Cathepsin S is a novel target for age-related dry eye.Experimental eye research · 2022Article
- Targeted Therapy for Primary Sjögren's Syndrome: Where are We Now?BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2021Review
- Population pharmacokinetic analysis of RO5459072, a low water-soluble drug exhibiting complex food-drug interactions.British journal of clinical pharmacology · 2021Article
- Proteomics Analysis of Tears and Saliva From Sjogren's Syndrome Patients.Frontiers in pharmacology · 2021Article
- Mapping Salivary Proteases in Sjögren's Syndrome Patients Reveals Overexpression of Dipeptidyl Peptidase-4/CD26.Frontiers in immunology · 2021Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivePrimary Sjögren syndrome (pSS) is characterized by T and B cell infiltration of exocrine glands. The cysteine protease cathepsin S (CatS) is crucially involved in MHCII processing and T cell stimulation, and elevated levels have been found in patients with RA, psoriasis and pSS. However, little is known about the functional characteristics and mechanisms of SS-A- and SS-B-specific T cells in pSS patients. We herein investigated the inhibition of CatS activity in different biocompartments of pSS patients including antigen-specific T cell responses.
methodsEx vivo CatS activity was assessed in tears, plasma and saliva of 15 pSS patients and 13 healthy controls (HC) and in the presence or absence of the specific CatS inhibitor RO5459072. In addition, antigen (SS-A (60kD), SS-B, influenza H
resultsCatS activity was significantly elevated in tear fluid, but not other biocompartments, was inversely associated with exocrinic function in pSS patients and could significantly be suppressed by RO5459072. Moreover, CatS inhibition by RO5459072 led to strong and dose-dependent suppression of SS-A/SS-B-specific T cell effector functions and cytokine secretion by CD14
conclusionCatS activity in tear fluid seems to be a relevant biomarker for pSS disease activity. Conversely, CatS inhibition diminishes T cell and associated monokine responses towards relevant autoantigens in pSS. Thus, CatS inhibition may represent a promising novel treatment strategy in pSS.
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