ArticleJournal of clinical immunology2022
An Immunological Axis Involving Interleukin 1β and Leucine-Rich-α2-Glycoprotein Reflects Therapeutic Response of Children with Kawasaki Disease: Implications from the KAWAKINRA Trial.
Article in Journal of clinical immunology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06697431 (A Randomized, Controlled, Open-label, Non Inferiority KawasakI Trial With Anakinra), which is not on this map. Cited by 22 papers, 2 of them syntheses 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.
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 Randomized, Controlled, Open-label, Non Inferiority KawasakI Trial With Anakinra
Who cites it
22 citing papers in PubMed, 2 syntheses or guidelines pooled it, 26 citations in OpenAlex.
- Anakinra for intravenous immunoglobulin-resistant Kawasaki disease: a systematic literature review.RMD open · 2026Pooled it
- Anakinra use in pediatric kawasaki disease: inflammation control, coronary artery outcomes, and safety.Pediatric rheumatology online journal · 2026Pooled it
- The Potential Role of Endothelial Cells in the Pathophysiology, Diagnosis, and Management of Acute Kawasaki Disease.CJC open · 2026Review
- Multiomics approaches in Kawasaki disease: insights into pathogenesis and emerging directions for diagnosis and treatment.Clinical and experimental pediatrics · 2026Article
- Neutrophil heterogeneity in Kawasaki disease and multisystem inflammatory syndrome in children.Pediatric research · 2026Review
- Expression of key genes in IVIG-unresponsive Kawasaki disease and their immune correlation based on bioinformatics analysis.Immunologic research · 2026Article
- Clinical Practice Variation Among Pediatric Rheumatologists Treating Kawasaki Disease: Results of a North American Survey.Children (Basel, Switzerland) · 2025Article
- Anakinra for infants under six months with Kawasaki disease and coronary artery lesions: a multicenter case series and literature review.Pediatric rheumatology online journal · 2025Article
- Mapping Drivers of Coronary Endothelial Activation and Endothelial-to-Mesenchymal Transition through Mimicking of Multimediator Inflammation in Kawasaki Disease Context.ACR open rheumatology · 2025Article
- Immunophenotype of Kawasaki Disease: Insights into Pathogenesis and Treatment Response.Life (Basel, Switzerland) · 2025Review
- An Update on Kawasaki Disease.Current rheumatology reports · 2024Review
- Article
- Predictive value of plasma sICAM-1 and sP-Selectins in the risk of death in patients with acute respiratory distress syndrome.Journal of medical biochemistry · 2024Article
- Differentiating Multisystem Inflammatory Syndrome in Children from Kawasaki Disease During the Pandemic.Turkish archives of pediatrics · 2024Article
- Review
- Utilizing T-Lymphocyte Activation-Related Cytokines to Predict Non-Responsiveness to Treatment in Pediatric Kawasaki Disease.Pediatric health, medicine and therapeutics · 2024Article
- The disruptive role of LRG1 on the vasculature and perivascular microenvironment.Frontiers in cardiovascular medicine · 2024Review
- Kawasaki Disease-Associated Cytokine Storm Syndrome.Advances in experimental medicine and biology · 2024Review
- Article
- Extracellular Matrix Remodeling in Vascular Disease: Defining Its Regulators and Pathological Influence.Arteriosclerosis, thrombosis, and vascular biology · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 6 institutions in 2 countries.
Funding
Abstract
purposeA recent phase II open-label study of the interleukin 1 (IL-1) receptor antagonist (IL-1Ra) anakinra in treating IVIG-resistant Kawasaki disease (KD) patients reported promising results. Here, we aimed to characterize the immunological impact of IL-1 blockade in this unique study population.
methodsPatients' and control sera and supernatants of cells (whole blood, neutrophils, coronary artery endothelial cells) stimulated with recombinant IL-1β were analyzed for single or multiple marker (n = 22) expression by ELISA or multiplexed bead array assay. Data were analyzed using unsupervised hierarchical clustering, multiple correlation, and multi-comparison statistics and were compared to retrospective analyses of KD transcriptomics.
resultsInflammation in IVIG-resistant KD (n = 16) is hallmarked by over-expression of innate immune mediators (particularly IL-6 > CXCL10 > S100A12 > IL-1Ra). Those as well as levels of immune or endothelial cell activation markers (sICAM-1, sVCAM-1) declined most significantly in course of anakinra treatment. Prior as well as following IL-1R blockade, over-expression of leucine-rich-α2-glycoprotein 1 (LRG1) associated best with remnant inflammatory activity and the necessity to escalate anakinra dosage and separated inflammatory KD patients from sJIA-MAS (n = 13) and MIS-C (n = 4). Protein as well as retrospective gene expression analyses indicated tight association of LRG1 with IL-1β signaling and neutrophilia, while particularly neutrophil stimulation with recombinant IL-1β resulted in concentration-dependent LRG1 release.
conclusionOur study identifies LRG1 as known trigger of endothelial activation and cardiac re-modeling to associate with IL-1β signaling in KD. Besides a potential patho-mechanistic implication of these findings, our data suggest blood leukocyte and neutrophil counts to best predict response to IL-1Ra treatment in IVIG-resistant KD.
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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.