ArticleArthritis research & therapy2019
Iguratimod represses B cell terminal differentiation linked with the inhibition of PKC/EGR1 axis.
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 26 papers, 2 of them syntheses that pooled it.
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Who cites it
26 citing papers in PubMed, 2 syntheses or guidelines pooled it, 87 citations in OpenAlex.
- Therapeutic potential of natural coumarins in autoimmune diseases with underlying mechanisms.Frontiers in immunology · 2024Pooled it
- Efficacy and safety of Iguratimod in the treatment of Ankylosing Spondylitis: A systematic review and meta-analysis of randomized controlled trials.Frontiers in immunology · 2023Pooled it
- Efficacy and safety of iguratimod in patients with primary Sjögren's syndrome: a multicentre randomised controlled trial.RMD open · 2025Trial
- The SMILE study: Study of long-term methotrexate and iguratimod combination therapy in early rheumatoid arthritis.Chinese medical journal · 2025Trial
- Efficacy and Safety of Iguratimod Supplement to the Standard Immunosuppressive Regimen in Highly Mismatched Renal Transplant Recipients: A Pilot Study.Frontiers in immunology · 2021Trial
- An iguratimod prodrug reduces RA-FLS invasiveness by disrupting STAT1-C3-TNFα-mediated crosstalk between fibroblast-like synoviocytes and macrophages.Journal of orthopaedic translation · 2026Article
- Iguratimod in Autoimmune Diseases: Emerging Evidence for its Immunomodulatory and Therapeutic Role.Mediterranean journal of rheumatology · 2026Review
- Comparison of the effect of iguratimod and hydroxychloroquine on regulatory B cells in the treatment of primary Sjögren's syndrome.Frontiers in medicine · 2025Article
- Iguratimod suppresses plasma cell differentiation and ameliorates experimental Sjögren's syndrome in mice by promoting TEC kinase degradation.Acta pharmacologica Sinica · 2024Article
- Decreased Expression of IL-35 and Its Receptor Contributes to Impaired Megakaryopoiesis in the Pathogenesis of Immune Thrombocytopenia.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Article
- Iguratimod suppresses Tfh cell differentiation in primary Sjögren's syndrome patients through inhibiting Akt/mTOR/STAT3 signaling.Arthritis research & therapy · 2023Article
- Iguratimod attenuated fibrosis in systemic sclerosis via targeting early growth response 1 expression.Arthritis research & therapy · 2023Article
- EGR1 induces EMT in pancreatic cancer via a P300/SNAI2 pathway.Journal of translational medicine · 2023Article
- Efficacy and safety of Iguratimod as an add-on therapy for refractory lupus nephritis: A preliminary investigational study.Frontiers in immunology · 2023Observational
- Research progress on the clinical application and mechanism of iguratimod in the treatment of autoimmune diseases and rheumatic diseases.Frontiers in immunology · 2023Review
- Iguratimod Restrains Circulating Follicular Helper T Cell Function by Inhibiting Glucose MetabolismFrontiers in immunology · 2022Article
- EGR1 Enhances Lymphangiogenesis via SOX18-Mediated Activation of JAK2/STAT3 Pathway.Computational and mathematical methods in medicine · 2022Article
- Trimethylamine N-Oxide Promotes Autoimmunity and a Loss of Vascular Function in Toll-like Receptor 7-Driven Lupus Mice.Antioxidants (Basel, Switzerland) · 2021Article
- Article
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundThis study aimed to explore the molecular mechanism and clinical relevance of iguratimod in the regulation of human B cell terminal differentiation.
methodsAn in vitro human antibody-secreting cell (ASC) differentiation system was established to test the effect of iguratimod. B cell phenotype and key transcription factors (TFs) relevant to ASC differentiation were analyzed through flow cytometry and qPCR. The COX-2 activity was measured by enzyme immunoassay (EIA). RNA sequencing was used to identify potential targets of iguratimod. We enrolled six treatment-naive rheumatoid arthritis (RA) patients whose blood samples were collected for phenotypic and molecular studies along with 12-week iguratimod monotherapy.
resultsIguratimod inhibited human ASC generation without affecting B cell activation and proliferation. Iguratimod showed only weak COX-2 activity. Gene set enrichment analysis (GSEA) identified that protein kinase C (PKC) pathway was targeted by iguratimod which was confirmed by PKC activity detection. Furthermore, early growth response 1 (EGR1), a target of PKC and a non-redundant TF for ASC differentiation, was found to be the most downregulated gene in iguratimod-treated B cells. Lastly, iguratimod monotherapy decreased peripheral ASCs and was associated with improved disease activity. The expression of major ASC-related TFs, including EGR1, was similarly downregulated in patient blood samples.
conclusionsIguratimod inhibits ASC differentiation both in vitro and in RA patients. Our study suggests that PKC/EGR1 axis, rather than COX-2, is critically involved in the inhibitory effect by iguratimod on human ASC differentiation. Iguratimod could have a broader application to treat B cell-related autoimmune diseases in clinics.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.