ArticleMolecular medicine (Cambridge, Mass.)2018
Changes in the process of alternative RNA splicing results in soluble B and T lymphocyte attenuator with biological and clinical implications in critical illness.
Article in Molecular medicine (Cambridge, Mass.), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 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
- RNA Sequencing of Sepsis Patients Informs Tests to Quickly Diagnose Pathogens and Resistance.Shock (Augusta, Ga.) · 2026Article
- Trends in complete blood count and derived inflammatory indices in ICU patients undergoing percutaneous tracheostomy: a retrospective exploratory study in Italy.Anaesthesiology intensive therapy · 2026Article
- The Search for Predictive Biomarkers in Response to Immune Checkpoint Inhibitors and Associated Adverse Events.Journal of personalized medicine · 2025Review
- Predicting nonsense-mediated mRNA decay from splicing events in sepsis using RNA-sequencing data.Life science alliance · 2025Article
- Mechanisms of immune suppression in sepsis/shock: one investigator's/lab group's experience (SLB 2024 legacy award presentation).Journal of leukocyte biology · 2025Article
- Lymphopenia in sepsis: a narrative review.Critical care (London, England) · 2024Review
- Soluble immune checkpoints: implications for cancer prognosis and response to immune checkpoint therapy and conventional therapies.Journal of experimental & clinical cancer research : CR · 2024Review
- Alternative splicing of modulatory immune receptors in T lymphocytes: a newly identified and targetable mechanism for anticancer immunotherapy.Frontiers in immunology · 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
- Early detection of soluble CD27, BTLA, and TIM-3 predicts the development of nosocomial infection in pediatric burn patients.Frontiers in immunology · 2022Observational
- Sustained elevation of soluble B- and T- lymphocyte attenuator predicts long-term mortality in patients with bacteremia and sepsis.PloS one · 2022Article
- The Role of B and T Lymphocyte Attenuator in Respiratory System Diseases.Frontiers in immunology · 2021Review
- Roles of BTLA in Immunity and Immune Disorders.Frontiers in immunology · 2021Review
- Soluble B7-CD28 Family Inhibitory Immune Checkpoint Proteins and Anti-Cancer Immunotherapy.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
- Review
- Clinical significance of circulating soluble immune checkpoint proteins in sorafenib-treated patients with advanced hepatocellular carcinoma.Scientific reports · 2020Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundCritically ill patients with sepsis and acute respiratory distress syndrome have severely altered physiology and immune system modifications. RNA splicing is a basic molecular mechanism influenced by physiologic alterations. Immune checkpoint inhibitors, such as B and T Lymphocyte Attenuator (BTLA) have previously been shown to influence outcomes in critical illness. We hypothesize altered physiology in critical illness results in alternative RNA splicing of the immune checkpoint protein, BTLA, resulting in a soluble form with biologic and clinical significance.
methodsSamples were collected from critically ill humans and mice. Levels soluble BTLA (sBTLA) were measured. Ex vivo experiments assessing for cellular proliferation and cytokine production were done using splenocytes from critically ill mice cultured with sBTLA. Deep RNA sequencing was done to look for alternative splicing of BTLA. sBTLA levels were fitted to models to predict sepsis diagnosis.
resultssBTLA is increased in the blood of critically ill humans and mice and can predict a sepsis diagnosis on hospital day 0 in humans. Alternative RNA splicing results in a premature stop codon that results in the soluble form. sBTLA has a clinically relevant impact as splenocytes from mice with critical illness cultured with soluble BTLA have increased cellular proliferation.
conclusionsBTLA is produced as a result of alternative RNA splicing. This isoform of BTLA has biological significance through changes in cellular proliferation and can predict the diagnosis of sepsis.
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