ArticleClinical and experimental immunology2024
A novel, high-performance, low-volume, rapid luciferase immunoprecipitation system (LIPS) assay to detect autoantibodies to zinc transporter 8.
Article in Clinical and experimental immunology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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9 citing papers in PubMed, 12 citations in OpenAlex.
- Universal capillary screening for chronic autoimmune, metabolic and cardiovascular diseases: feasibility and acceptability of the UNISCREEN study.Frontiers in public health · 2025Trial
- Natural history study of type 1 diabetes risk in adults (T1DRA): protocol for screening and follow-up of UK adults.BMJ open · 2026Article
- Article
- Evolution of islet autoantibodies in the Environmental Determinants of Islet Autoimmunity (ENDIA) prospective cohort.Diabetologia · 2026Article
- Early Detection of Pediatric Type 1 Diabetes: The Expanding Role of Screening.Children (Basel, Switzerland) · 2026Review
- Induction of immune education in type 1 diabetes through controlled allogeneic islet rejection at onset: a monocentric open-label pilot study.EClinicalMedicine · 2025Article
- From Prediction to Prevention: The Intricacies of Islet Autoantibodies in Type 1 Diabetes.Current diabetes reports · 2025Review
- Type 1 diabetes diagnosed during pregnancy-an unusual but important challenge: a case series and review of literature.Frontiers in medicine · 2025Article
- Observational
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8 authors at 8 institutions in 2 countries.
Funding
Abstract
backgroundZinc transporter 8 autoantibodies (ZnT8A) are thought to appear close to type 1 diabetes (T1D) onset and can identify high-risk multiple (≥2) autoantibody positive individuals. Radiobinding assays (RBA) are widely used for ZnT8A measurement but have limited sustainability. We sought to develop a novel, high-performance, non-radioactive luciferase immunoprecipitation system (LIPS) assay to replace RBA.
methodsA custom dual C-terminal ZnT8 (aa268-369; R325/W325) heterodimeric antigen, tagged with a NanoluciferaseTM (Nluc-ZnT8) reporter, and LIPS assay was developed. Assay performance was evaluated by testing sera from new onset T1D (n = 573), healthy schoolchildren (n = 521), and selected first-degree relatives (FDRs) from the Bart's Oxford family study (n = 617; 164 progressed to diabetes).
resultsIn new-onset T1D, ZnT8A levels by LIPS strongly correlated with RBA (Spearman's r = 0.89; P < 0.0001), and positivity was highly concordant (94.3%). At a high specificity (95%), LIPS and RBA had comparable assay performance [LIPS pROC-AUC(95) 0.032 (95% CI: 0.029-0.036); RBA pROC-AUC(95) 0.031 (95% CI: 0.028-0.034); P = 0.376]. Overall, FDRs found positive by LIPS or RBA had a comparable 20-year diabetes risk (52.6% and 59.7%, respectively), but LIPS positivity further stratified T1D risk in FDRs positive for at least one other islet autoantibody detected by RBA (P = 0.0346).
conclusionThis novel, high-performance, cheaper, quicker, higher throughput, low blood volume Nluc-ZnT8 LIPS assay is a safe, non-radioactive alternative to RBA with enhanced sensitivity and ability to discriminate T1D progressors. This method offers an advanced approach to current strategies to screen the general population for T1D risk for immunotherapy trials and to reduce rates of diabetic ketoacidosis at diagnosis.
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