ABSTRACT Background First‐degree relatives (FDRs) of individuals with type 1 diabetes (T1D) carry a significantly elevated risk of developing autoimmune diseases, including celiac disease (CD) and autoimmune thyroid disease (AITD). The DiaUnion 1.0 study aimed to characterize one‐time autoantibodies, genetic risk profiles and long‐term progression to T1D, CD or AITD in siblings of children newly diagnosed with T1D. Methods Between 1997 and 2010, 1427 Danish siblings provided plasma and DNA samples to the DanDiabKids biobank. Autoantibodies associated with T1D (GADA, IAA, IA2A, ZnT8A), CD (tTGA) and AITD (TPOA) were measured using ADAP technology and confirmed by radiobinding assays. Genotyping was performed to compute a T1D Genetic Risk Score (GRS). National registry data were used to track disease incidence up to year 2024. Results Out of 1417 screened samples, 7.8% were positive for islet autoantibodies (IAab), and 4.6% had multiple IAab. Disease incidence rate increased substantially with IAab positivity: 0.11 per 100 person‐years in IAab‐negative siblings, 2.46 in single‐IAab positive and 8.10 in those with multiple IAab. Similarly, 1.97 per 100 person‐years of tTGA‐positive siblings developed CD, and 0.69 per 100 person‐years of TPOA‐positive individuals developed AITD. Higher GRS and HLA DR3/DR4 haplotypes were associated with autoantibody positivity (p < 0.0001). Conclusions A single screening for T1D, CD and AITD autoantibodies combined with genetic risk scoring stratified long‐term risk of clinically diagnosed autoimmune disease. These findings support further evaluation of targeted screening and follow‐up strategies in FDRs to enable surveillance and potential early intervention before clinical onset.
J. Christensen, G. Petersen, Simranjeet Kaur et al.· Diabetes, obesity and metabo...· 0 citations
The appearance of disease‑specific autoantibodies (Aab) is a hallmark of celiac disease (CeD). The recent adaption of a no‑biopsy approach places greater reliance on Aab testing. Despite their widespread use, conventional assay formats such as enzyme-linked immunosorbent assays (ELISA) continue to exhibit inherent methodological deficiencies that cannot be readily mitigated. Radio-binding assays (RBA) have historically defined the benchmark for assay performance, but the requirement for radiolabeled reagents and dedicated facilities renders this strategy an untenable solution beyond a limited number of specialized laboratories. This review aims to outline the future role of Aab in the diagnostic algorithm of CeD and to highlight the next-generation techniques that could replace the conventional testing methods. We discuss the diagnostic utility of ELISA, RBA, Electrochemiluminescence assay (ECL), luciferase immunoprecipitation systems (LIPS), antibody detection by agglutination polymerase chain reaction (ADAP) and dissociation enhanced lanthanide fluorescence immunoassay (DELFIA) techniques with emphasis on measuring anti-Transglutaminase 2 (TG2) Aab in the diagnosis of CeD. With the advantages of automation and multiplexing, the new generation of Aab testing modalities like ECL and ADAP may demonstrate sufficient sensitivity and accuracy to warrant inclusion in future CeD diagnostic guidelines. While multiplexing allows the inclusion of multiple Aabs testing from small volumes of blood in an automated manner, this generation of immunoassays are well suited for large-scale screenings and may replace the conventional ELISA and RBA techniques in the near future.
A. Lomash, Alexander Lind, K. Kurppa et al.· Annals medicus· 0 citations
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