ArticlePloS one2017
Soluble B and T Lymphocyte Attenuator Correlates to Disease Severity in Sepsis and High Levels Are Associated with an Increased Risk of Mortality.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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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.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.
- Inhibitory Immune Checkpoint Molecule Expression in Clinical Sepsis Studies: A Systematic Review.Critical care medicine · 2020Pooled it
- Association between B and T lymphocyte attenuator/herpes virus entry mediator immunoregulatory axis and outcome prediction in a mixed critically ill population.Scientific reports · 2026Article
- Early biomarkers for predicting sepsis-induced shock: insights from inflammatory pathways and immune response.Frontiers in pharmacology · 2026Review
- BTLA biology in cancer: from bench discoveries to clinical potentials.Biomarker research · 2024Review
- From immune dysregulation to organ dysfunction: understanding the enigma of Sepsis.Frontiers in microbiology · 2024Review
- Beyond the anti-PD-1/PD-L1 era: promising role of the BTLA/HVEM axis as a future target for cancer immunotherapy.Molecular cancer · 2023Review
- Pneumonia in the first week after polytrauma is associated with reduced blood levels of soluble herpes virus entry mediator.Frontiers in immunology · 2023Article
- MK2 Inhibitors as a Potential Crohn's Disease Treatment Approach for Regulating MMP Expression, Cleavage of Checkpoint Molecules and T Cell Activity.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Soluble PD-L1 in blood correlates positively with neutrophil and negatively with lymphocyte mRNA markers and implies adverse sepsis outcome.Immunologic research · 2022Article
- Sustained elevation of soluble B- and T- lymphocyte attenuator predicts long-term mortality in patients with bacteremia and sepsis.PloS one · 2022Article
- The Neonatal Innate Immune Response to Sepsis: Checkpoint Proteins as Novel Mediators of This Response and as Possible Therapeutic/Diagnostic Levers.Frontiers in immunology · 2022Review
- Early detection of soluble CD27, BTLA, and TIM-3 predicts the development of nosocomial infection in pediatric burn patients.Frontiers in immunology · 2022Observational
- Article
- Correlation of sPD1 with Procalcitonin and C-Reactive Protein Levels in Patients with Sepsis.Cell journal · 2021Article
- Roles of BTLA in Immunity and Immune Disorders.Frontiers in immunology · 2021Review
- sCD28, sCD80, sCTLA-4, and sBTLA Are Promising Markers in Diagnostic and Therapeutic Approaches for Aseptic Loosening and Periprosthetic Joint Infection.Frontiers in immunology · 2021Article
- The Role of B and T Lymphocyte Attenuator in Respiratory System Diseases.Frontiers in immunology · 2021Review
- Immune Checkpoints: Novel Therapeutic Targets to Attenuate Sepsis-Induced Immunosuppression.Frontiers in immunology · 2020Review
- Rs1982809 is a functional biomarker for the prognosis of severe post-traumatic sepsis and MODs.Experimental biology and medicine (Maywood, N.J.) · 2019Article
- Treatment with Recombinant Interleukin-15 (IL-15) Increases the Number of T Cells and Natural Killer (NK) Cells and Levels of Interferon-γ (IFN-γ) in a Rat Model of Sepsis.Medical science monitor : international medical journal of experimental and clinical research · 2019Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
INTRODUCTION AND
aimsB- and T-lymphocyte Attenuator (BTLA), Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and Programmed Death 1 (PD-1) are co-inhibitory receptors that regulate T cell activation. In the present study of ICU-treated patients we measured plasma concentrations of their soluble isoforms, with the aim to evaluate their potential as sepsis biomarkers and utility as prognostic indicators.
methods101 patients with sepsis, 28 patients with non-infectious critical illness (ICU controls) and 31 blood donors (healthy controls, HC) were included in the study. Plasma concentrations of soluble BTLA (sBTLA), CTLA-4 (sCTLA-4) and PD-1 (sPD-1) were measured with ELISA in serial blood samples. Comparisons were made with Mann-Whitney U test and correlations were assessed with Spearman's Rank correlation test. Cox proportional hazard models, with sBTLA and sPD-1 as fixed and sBTLA as time-varying covariates, were used to determine association with 28-day mortality.
resultssBTLA levels were significantly higher in the sepsis cohort (median 14 ng/mL, IQR 8-29) compared to ICU controls (9 ng/mL, IQR 5-26, p = 0.048) and HC (2.9 ng/mL, IQR 0.9-9.1, p<0.01), and correlated to SOFA score. sBTLA levels were higher in 28 day sepsis non-survivors than in survivors (baseline median 28 ng/mL, IQR 13-41 vs 13 ng/mL, IQR 8-23, p = 0.04). After adjustment for age and comorbidities, the relative risk of 28 day mortality was nearly 5-fold higher in sepsis patients with a baseline sBTLA > 21 ng/mL, compared to those with a level below this threshold. sBTLA was even more associated with mortality in the time-varying analysis. sPD-1 levels were lower in the sepsis cohort compared to HC but not compared to ICU controls and were not associated with mortality. sCTLA-4 was detectable in only one subject.
conclusionPlasma concentrations of soluble BTLA were increased early in sepsis/septic shock and correlated to severity of disease. A baseline concentration >21ng/mL was associated with a poor prognosis.
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Registered trials
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