ArticleJCI insight2022
Circulating platelet-neutrophil aggregates characterize the development of type 1 diabetes in humans and NOD mice.
Article in JCI insight, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
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Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 44 citations in OpenAlex.
- A proteomic meta-analysis refinement of plasma extracellular vesicles.Scientific data · 2023Pooled it
- Biomarkers of partial remission in paediatric type 1 diabetes: β-cell stress, immune-metabolic remodelling, and translational priorities-a narrative review.Translational pediatrics · 2026Review
- Neutrophils and neutrophil extracellular traps in diabetes mellitus and its complications: Mechanisms and therapeutic implications.iScience · 2026Review
- The small-molecule Syk inhibitor R788 inhibits hematopoiesis and worsens anemia in sickle cell disease mice.Blood vessels, thrombosis & hemostasis · 2026Article
- Integrative serum proteomic and metabolomic profiling in ovarian endometrioma: an exploratory multi-omics study.Frontiers in medicine · 2026Article
- Metabolic Adaptation of CD8⁺ T Cells Limits the Efficacy of Fatty Acid Oxidation Inhibition in Type 1 Diabetes.International journal of biological sciences · 2026Article
- P-Selectin and Platelet-Monocyte Interaction in Inflammation: Mechanisms, Hypothesis, and Open Questions.Journal of inflammation research · 2026Review
- Live fast, die young: neutrophils streamline their metabolism to maximize inflammation.Infection and immunity · 2025Review
- NETosis in hypersensitivity disorders.Molecular biology reports · 2025Review
- Transient Inflammation of Pancreatic Exocrine Tissue in Autoimmune Diabetes Follows Onset of Islet Damage and Utilizes Heparanase-1.International journal of molecular sciences · 2025Article
- Neutrophils in Type 1 Diabetes: Untangling the Intricate Web of Pathways and Hypothesis.Biomolecules · 2025Review
- Tissue Resident and Infiltrating Immune Cells: Their Influence on the Demise of Beta Cells in Type 1 Diabetes.Biomolecules · 2025Review
- Review
- Article
- Beyond inflammation: the multifaceted therapeutic potential of targeting the CXCL8-CXCR1/2 axis in type 1 diabetes.Frontiers in immunology · 2025Review
- NETs: a new target for autoimmune disease.Frontiers in immunology · 2025Review
- Structured adaptive boosting trees for detection of multicellular aggregates in fluorescence intravital microscopy.Microvascular research · 2024Article
- A dose-adjusted, open-label, pilot study of the safety, tolerability, and pharmacokinetics of STC3141 in critically ill patients with sepsis.Pharmacology research & perspectives · 2024Article
- The differential formation and composition of leukocyte-platelet aggregates induced by various cellular stimulants.Thrombosis research · 2024Article
- Refined protocol for newly onset identification in non-obese diabetic mice: an animal-friendly, cost-effective, and efficient alternative.Laboratory animal research · 2024Article
Corrections and comments
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Authors and funding
21 authors at 6 institutions in 3 countries.
Funding
Abstract
Platelet-neutrophil aggregates (PNAs) facilitate neutrophil activation and migration and could underpin the recruitment of neutrophils to the pancreas during type 1 diabetes (T1D) pathogenesis. PNAs, measured by flow cytometry, were significantly elevated in the circulation of autoantibody-positive (Aab+) children and new-onset T1D children, as well as in pre-T1D (at 4 weeks and 10-12 weeks) and T1D-onset NOD mice, compared with relevant controls, and PNAs were characterized by activated P-selectin+ platelets. PNAs were similarly increased in pre-T1D and T1D-onset NOD isolated islets/insulitis, and immunofluorescence staining revealed increased islet-associated neutrophil extracellular trap (NET) products (myeloperoxidase [MPO] and citrullinated histones [CitH3]) in NOD pancreata. In vitro, cell-free histones and NETs induced islet cell damage, which was prevented by the small polyanionic drug methyl cellobiose sulfate (mCBS) that binds to histones and neutralizes their pathological effects. Elevated circulating PNAs could, therefore, act as an innate immune and pathogenic biomarker of T1D autoimmunity. Platelet hyperreactivity within PNAs appears to represent a previously unrecognized hematological abnormality that precedes T1D onset. In summary, PNAs could contribute to the pathogenesis of T1D and potentially function as a pre-T1D diagnostic.
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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.