ArticleArthritis research & therapy2014
Soluble OX40L is associated with presence of autoantibodies in early rheumatoid arthritis.
Article in Arthritis research & therapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00660647 (Optimized Treatment Algorithm in Early Rheumatoid Arthritis), which is not on this map. Cited by 16 papers.
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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.
Optimized Treatment Algorithm in Early Rheumatoid Arthritis: Methotrexate and Intra-articular Glucocorticosteroid Plus Adalimumab or Placebo in the Treatment of Early Rheumatoid Arthritis
Who cites it
16 citing papers in PubMed, 39 citations in OpenAlex.
- Immune checkpoint imbalance in ANCA-associated vasculitis: insights into disease activity and precision immunotherapy.Frontiers in medicine · 2026Review
- Regulatory T Cell-Based Adoptive Cell Therapy in Autoimmunity.International journal of molecular sciences · 2025Review
- A Phase I Clinical Trial Adding OX40 Agonism to In Situ Therapeutic Cancer Vaccination in Patients with Low-Grade B-cell Lymphoma Highlights Challenges in Translation from Mouse to Human Studies.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Human OX40L-CAR-TScience translational medicine · 2024Article
- Immune checkpoints in rheumatoid arthritis: progress and promise.Frontiers in immunology · 2023Review
- The Germinal Center Milieu in Rheumatoid Arthritis: The Immunological Drummer or Dancer?International journal of molecular sciences · 2021Review
- Hsa_circ_0000652 Aggravates Inflammation by Activation of Macrophages and Enhancement of OX40/OX40L Interaction in Ankylosing Spondylitis.Frontiers in cell and developmental biology · 2021Article
- The OX40 Axis is Associated with Both Systemic and Local Involvement in Atopic Dermatitis.Acta dermato-venereologica · 2020Article
- Therapeutic strategies for the costimulatory molecule OX40 in T-cell-mediated immunity.Acta pharmaceutica Sinica. B · 2020Review
- Enhancement of the Soluble Form of OX40 and OX40L Costimulatory Molecules but Reduction of the Membrane Form in Type 1 Diabetes (T1D).Journal of immunology research · 2019Article
- Increased Expressions of OX40 and OX40 Ligand in Patients with Primary Immune Thrombocytopenia.Journal of immunology research · 2019Article
- Toward Small-Molecule Inhibition of Protein-Protein Interactions: General Aspects and Recent Progress in Targeting Costimulatory and Coinhibitory (Immune Checkpoint) Interactions.Current topics in medicinal chemistry · 2018Review
- The Ox40/Ox40 Ligand Pathway Promotes Pathogenic Th Cell Responses, Plasmablast Accumulation, and Lupus Nephritis in NZB/W F1 Mice.Journal of immunology (Baltimore, Md. : 1950) · 2017Article
- Beyond TNF: TNF superfamily cytokines as targets for the treatment of rheumatic diseases.Nature reviews. Rheumatology · 2017Review
- Association between circulating inflammatory molecules and alcoholic liver disease in men.Cell stress & chaperones · 2016Article
- OX40, OX40L and Autoimmunity: a Comprehensive Review.Clinical reviews in allergy & immunology · 2016Review
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionOX40 and its ligand OX40L are key components in the generation of adaptive memory response and provide necessary co-stimulatory signals for activated effector T cells. Here we investigate the dual roles of the membrane and soluble (s) forms of OX40 and OX40L in plasma and synovial fluid and their association with autoantibodies and disease activity in rheumatoid arthritis (RA).
methodsSoluble OX40 and sOX40L plasma levels were measured in treatment-naïve early RA patients (eRA) at baseline and after 3, 6, and 12 months of treatment with methotrexate and adalimumab (n = 39) and with methotrexate alone (n = 37). Adalimumab was discontinued after the first year, and patients were followed for additional 12 months. For comparison, sOX40 and sOX40L were measured in patients with chronic RA (cRA, n = 15) and healthy volunteers (HV, n = 34). Membrane-bound OX40 and OX40L expression on T cells, B cells and monocytes were quantified.
resultsSoluble OX40 plasma levels of eRA patients were not different at the time of treatment initiation, but were significantly higher after 12 months of treatment, compared with HV or cRA patients. Soluble OX40L was significantly elevated throughout the first 12 months of treatment compared with HVs and patients with cRA. Adalimumab treatment did not influence sOX40 or sOX40L plasma levels. At baseline, sOX40L levels were strongly associated with the presence of anti-citrullinated protein antibodies (ACPA) (P <0.001) and IgM-RF (P <0.0001). The sOX40/sOX40L ratio was decreased in eRA, and a low ratio at the time of adalimumab discontinuation was associated with increased DAS28CRP and risk of flare the following year. T cells in the synovial fluid had the highest expression of OX40, while monocytes and B cells were the main expressers of OX40L in the joint.
conclusionsPlasma levels of sOX40 and sOX40L were increased in eRA and sOX40L was correlated with ACPA and IgM-RF. Further, expression of membrane-bound OX40 and OX40L was increased in eRA and cRA. Combined, these findings could reflect that increased activity in the OX40 systems facilitate to drive disease activity and autoantibody production in RA.
trial registrationClincaltrials.gov NCT00660647, 10 April 2008.
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