ReviewFrontiers in immunology2018
Targeting Costimulatory Pathways in Systemic Sclerosis.
Review in Frontiers in immunology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02161406 (A Phase 2 Study to Evaluate Subcutaneous Abatacept vs. Placebo in Diffuse Cutaneous Systemic Sclerosis- a Double-blind, Placebo-controlled, Randomized Controlled Trial.), which is not on this map. Cited by 22 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.
A Phase 2 Study to Evaluate Subcutaneous Abatacept vs. Placebo in Diffuse Cutaneous Systemic Sclerosis- a Double-blind, Placebo-controlled, Randomized Controlled Trial.
Who cites it
22 citing papers in PubMed, 47 citations in OpenAlex.
- A Phase 1 Study of KHK4083: A Single-Blind, Randomized, Placebo-Controlled Single-Ascending-Dose Study in Healthy Adults and an Open-Label Multiple-Dose Study in Patients With Ulcerative Colitis.Clinical pharmacology in drug development · 2021Trial
- Extended clinical and immunological phenotype and transplant outcome in CD27 and CD70 deficiency.Blood · 2020Trial
- Revisiting the CD40-CD40L axis: from mechanistic insight to therapeutic renewal in autoimmune disease.Current opinion in rheumatology · 2026Review
- Exosomes as Precise Regulators of the Osteoimmune Microenvironment: Engineering Strategies for Bone Regeneration.Biomaterials research · 2026Review
- Severe overlap of morphea and lichen sclerosus after anti-PD-L1 immunotherapy in small cell lung cancer.Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG · 2025Article
- T-cell immune status in patients with acute exacerbation of chronic obstructive pulmonary disease: a case-control study.Frontiers in medicine · 2025Article
- STING-STAT6 Signaling Pathway Promotes IL-4Immune network · 2024Article
- Biomarkers reflecting the pathogenesis, clinical manifestations, and guide therapeutic approach in systemic sclerosis: a narrative review.Clinical rheumatology · 2024Review
- Sclerotic-Type Cutaneous Chronic Graft-Versus-Host Disease Exhibits Activation of T Helper 1 and OX40 Cytokines.The Journal of investigative dermatology · 2024Article
- Novel role of long non-coding RNAs in autoimmune cutaneous disease.Journal of cell communication and signaling · 2022Review
- Increased Levels of ICOS and ICOSL Are Associated to Pulmonary Arterial Hypertension in Patients Affected by Connective Tissue Diseases.Diagnostics (Basel, Switzerland) · 2022Article
- Acazicolcept (ALPN-101), a dual ICOS/CD28 antagonist, demonstrates efficacy in systemic sclerosis preclinical mouse models.Arthritis research & therapy · 2022Article
- CD4Frontiers in immunology · 2022Review
- Toward Molecular Stratification and Precision Medicine in Systemic Sclerosis.Frontiers in medicine · 2022Review
- Autoinflammation and autoimmunity across rheumatic and musculoskeletal diseases.Nature reviews. Rheumatology · 2021Review
- CD27 enhances the killing effect of CAR T cells targeting trophoblast cell surface antigen 2 in the treatment of solid tumors.Cancer immunology, immunotherapy : CII · 2021Article
- Metformin ameliorates scleroderma via inhibiting Th17 cells and reducing mTOR-STAT3 signaling in skin fibroblasts.Journal of translational medicine · 2021Article
- Emerging drugs for the treatment of scleroderma: a review of recent phase 2 and 3 trials.Expert opinion on emerging drugs · 2020Review
- T cells in SSc skin lesions: knowing your enemy.Nature reviews. Rheumatology · 2020Article
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Systemic sclerosis (SSc) is an autoimmune T-cell disease that is characterized by pathological fibrosis of the skin and internal organs. SSc is considered a prototype condition for studying the links between autoimmunity and fibrosis. Costimulatory pathways such as CD28/CTLA-4, ICOS-B7RP1, CD70-CD27, CD40-CD154, or OX40-OX40L play an essential role in the modulation of T-cell and inflammatory immune responses. A growing body of evidence suggests that T-cell costimulation signals might be implicated in the pathogenesis of SSc. CD28, CTLA-4, ICOS, and OX40L are overexpressed in patients with SSc, particularly in patients with cutaneous diffuse forms. In pre-clinical models of SSc, T-cell costimulation blockade with abatacept (CTLA-4-Ig) prevented and induced the regression of inflammation-driven dermal fibrosis, improved digestive involvement, prevented lung fibrosis, and attenuated pulmonary hypertension in complementary models of SSc. Likewise, potent anti-fibrotic effects were seen with the blockade of OX40L by reducing the infiltration of inflammatory cells into lesional tissues leading to decreased fibroblast activation. Concerning clinical effects, a preliminary observational study suggested some effectiveness of abatacept on inflammatory joint involvement, whereas clinical improvement of skin fibrosis was observed in a small placebo-controlled randomized trial. Currently there is one ongoing phase II clinical trial assessing the efficacy of abatacept in SSc (ASSET trial, NCT02161406). Overall, given the lack of available effective agents and the known toxic effects of immunosuppressive agents approved for use in SSc, costimulatory pathways offer the advantage of a targeted approach to costimulatory signals and potentially a better safety profile.
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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.