ArticlePloS one2018
Immune checkpoint inhibitor PD-1 pathway is down-regulated in synovium at various stages of rheumatoid arthritis disease progression.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers, 2 of them syntheses that pooled it.
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
64 citing papers in PubMed, 2 syntheses or guidelines pooled it, 109 citations in OpenAlex.
- Pooled it
- Management of immune checkpoint inhibitor-related rheumatic adverse events.Thoracic cancer · 2020Pooled it
- Preexisting autoimmune disease and immune-related adverse events associated with anti-PD-1 cancer immunotherapy: a national case series from the Canadian Research Group of Rheumatology in Immuno-Oncology.Cancer immunology, immunotherapy : CII · 2021Trial
- Autoantibody-positive healthy individuals with lower lupus risk display a unique immune endotype.The Journal of allergy and clinical immunology · 2020Trial
- Immune Checkpoint Inhibitor-Associated Inflammatory Arthritis.Arthritis & rheumatology (Hoboken, N.J.) · 2026Review
- Cytokine-induced PD-L1 and PD-L2 expression is preserved but reverse signalling is altered in rheumatoid arthritis fibroblast-like synoviocytes.Arthritis research & therapy · 2026Article
- The TIM-3/Gal-9 Pathway: A Promising Therapeutic Target for Regulation of Immune Checkpoint in Rheumatoid Arthritis.Current rheumatology reviews · 2026Review
- Nanomedicine targeting the PD-1/PD-L1 axis in autoimmune diseases: breaking conventional barriers to restore immune tolerance.Journal of nanobiotechnology · 2025Review
- Association of Soluble Immune Checkpoint Molecules PD1 and 4-1BB With CTLA-4Ig Treatment Response in Early Rheumatoid Arthritis.ACR open rheumatology · 2025Article
- SLAM receptors regulate immune checkpoints via SAP and EAT- 2 in rheumatoid arthritis: association with disease activity.Clinical rheumatology · 2025Article
- Immune checkpoint inhibitors: From friend to foe.Toxicology reports · 2025Article
- Safety, tolerability, and efficacy of the PD-1 agonist antibody JNJ-67484703 in adults with active rheumatoid arthritis: results of a multicenter, double-blind, placebo-controlled, randomized, multiple-dose phase Ib study.Therapeutic advances in musculoskeletal disease · 2025Article
- Citrullinated peptides as drug candidates for rheumatoid arthritis.Frontiers in immunology · 2025Review
- The clinical characteristics, mechanism and management of immune checkpoint inhibitor-related arthritis.Frontiers in immunology · 2025Review
- Immune checkpoint-induced arthritis: a comprehensive single-cohort descriptive analysis from clinical evaluation to histology.Frontiers in medicine · 2025Article
- Exploring the Role of PD-1 in the Autoimmune Response: Insights into Its Implication in Systemic Lupus Erythematosus.International journal of molecular sciences · 2024Review
- A Study on the Immunoregulatory Role of the PD1 Pathway in Juvenile Idiopathic Arthritis.Mediterranean journal of rheumatology · 2024Article
- Association of plasma sPD-1 and sPD-L1 with disease status and future relapse in AQP4-IgG (+) NMOSD.Annals of clinical and translational neurology · 2024Article
- Insufficient PD-1 expression during active autoimmune responses: a deep single-cell proteomics analysis in inflammatory arthritis.Frontiers in immunology · 2024Article
- Design, Synthesis, and Biological Evaluation of Small-Molecule-Based Radioligands with Improved Pharmacokinetic Properties for Imaging of Programmed Death Ligand 1.Journal of medicinal chemistry · 2023Article
4 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
21 authors at 6 institutions in 4 countries.
Funding
Abstract
Immune checkpoint blockade with therapeutic anti-cytotoxic T lymphocyte-associated antigen (CTLA)-4 (Ipilimumab) and anti-programmed death (PD)-1 (Nivolumab and Pembrolizumab) antibodies alone or in combination has shown remarkable efficacy in multiple cancer types, concomitant with immune-related adverse events, including arthralgia and inflammatory arthritis (IA) in some patients. Herein, using Nivolumab (anti-PD-1 antagonist)-responsive genes along with transcriptomics of synovial tissue from multiple stages of rheumatoid arthritis (RA) disease progression, we have interrogated the activity status of PD-1 pathway during RA development. We demonstrate that the expression of PD-1 was increased in early and established RA synovial tissue compared to normal and OA synovium, whereas that of its ligands, programmed death ligand-1 (PD-L1) and PD-L2, was increased at all the stages of RA disease progression, namely arthralgia, IA/undifferentiated arthritis, early RA and established RA. Further, we show that RA patients expressed PD-1 on a majority of synovial tissue infiltrating CD4+ and CD8+ T cells. Moreover, enrichment of Nivolumab gene signature was observed in IA and RA, indicating that the PD-1 pathway was downregulated during RA disease progression. Furthermore, serum soluble (s) PD-1 levels were increased in autoantibody positive early RA patients. Interestingly, most of the early RA synovium tissue sections showed negative PD-L1 staining by immunohistochemistry. Therefore, downregulation in PD-1 inhibitory signaling in RA could be attributed to increased serum sPD-1 and decreased synovial tissue PD-L1 levels. Taken together, these data suggest that agonistic PD1 antibody-based therapeutics may show efficacy in RA treatment and interception.
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.