ArticleJCI insight2017
Btk-specific inhibition blocks pathogenic plasma cell signatures and myeloid cell-associated damage in IFN
Article in JCI insight, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
44 citing papers in PubMed, 72 citations in OpenAlex.
- Fenebrutinib in HNature medicine · 2021Trial
- Can we cure autoimmunity?Current opinion in immunology · 2026Review
- BTK-Inhibitor Loaded Polymeric Nanoparticles Alleviate Systemic Lupus Erythematosus by Targeting Elimination of Autoreactive BAFFRInternational journal of molecular sciences · 2026Article
- Inhibition of bruton's tyrosine kinase directly alleviates pathogenic CD4+ T cell response via PPAR-γ signaling in autoimmune uveitis.Journal of neuroinflammation · 2025Article
- FCRL5, a B-Cell Marker With Novel Diagnostic and Prognostic Value for Multiple Sclerosis.Neurology(R) neuroimmunology & neuroinflammation · 2025Article
- Review
- Review
- Review
- The conneXion between sex and immune responses.Nature reviews. Immunology · 2024Review
- Single-cell mass cytometry in immunological skin diseases.Frontiers in immunology · 2024Review
- Bruton's tyrosine kinase-bearing B cells and microglia in neuromyelitis optica spectrum disorder.Journal of neuroinflammation · 2023Article
- Biomarkers Associated with Drugs for the Treatment of Lupus Nephritis.Biomolecules · 2023Review
- Repurposing MS immunotherapies for CIDP and other autoimmune neuropathies: unfulfilled promise or efficient strategy?Therapeutic advances in neurological disorders · 2023Review
- Bruton's Kinase Inhibitors for the Treatment of Immunological Diseases: Current Status and Perspectives.Journal of clinical medicine · 2022Review
- Ulcerative colitis is characterized by a plasmablast-skewed humoral response associated with disease activity.Nature medicine · 2022Article
- BTK inhibition limits B-cell-T-cell interaction through modulation of B-cell metabolism: implications for multiple sclerosis therapy.Acta neuropathologica · 2022Article
- Targeted Therapy for Primary Sjögren's Syndrome: Where are We Now?BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2021Review
- Recent Advances in BTK Inhibitors for the Treatment of Inflammatory and Autoimmune Diseases.Molecules (Basel, Switzerland) · 2021Review
- Altered expression of genes controlling metabolism characterizes the tissue response to immune injury in lupus.Scientific reports · 2021Article
- Effective, safe, and sustained correction of murine XLA using a UCOE-BTK promoter-based lentiviral vector.Molecular therapy. Methods & clinical development · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
32 authors at 7 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Systemic lupus erythematosus (SLE) is often associated with exaggerated B cell activation promoting plasma cell generation, immune-complex deposition in the kidney, renal infiltration of myeloid cells, and glomerular nephritis. Type-I IFNs amplify these autoimmune processes and promote severe disease. Bruton's tyrosine kinase (Btk) inhibitors are considered novel therapies for SLE. We describe the characterization of a highly selective reversible Btk inhibitor, G-744. G-744 is efficacious, and superior to blocking BAFF and Syk, in ameliorating severe lupus nephritis in both spontaneous and IFNα-accelerated lupus in NZB/W_F1 mice in therapeutic regimens. Selective Btk inhibition ablated plasmablast generation, reduced autoantibodies, and - similar to cyclophosphamide - improved renal pathology in IFNα-accelerated lupus. Employing global transcriptional profiling of spleen and kidney coupled with cross-species human modular repertoire analyses, we identify similarities in the inflammatory process between mice and humans, and we demonstrate that G-744 reduced gene expression signatures essential for splenic B cell terminal differentiation, particularly the secretory pathway, as well as renal transcriptional profiles coupled with myeloid cell-mediated pathology and glomerular plus tubulointerstitial disease in human glomerulonephritis patients. These findings reveal the mechanism through which a selective Btk inhibitor blocks murine autoimmune kidney disease, highlighting pathway activity that may translate to human SLE.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.