Feasibility and performance of minimal-volume capillary blood screening for type 1 diabetes and coeliac disease autoantibodies across all age groups: the UNISCREEN population study

AIMS/HYPOTHESIS: The UNISCREEN study investigated the feasibility of minimally invasive capillary blood sampling combined with novel antibody tests for population-wide screening of type 1 diabetes and coeliac disease autoantibodies across all age groups, with secondary objectives to evaluate the prevalence and age-related distribution of these autoantibodies in a general Northern Italian population. METHODS: Between April and October 2023, we screened 1532 residents (50.1% of eligible population) of Cantalupo, Milan, aged 1-100 years. Capillary blood samples were collected by fingerprick from all participants. A subset of 20 autoantibody-positive individuals provided confirmatory venous samples. Islet autoantibody screening employed a novel solid-phase capture luciferase immunoprecipitation system (LIPS) 3-screen assay requiring only 1 μl of serum for simultaneous detection of GADA, IA-2A and ZnT8A, plus a separate IAA assay. Positive samples underwent confirmatory testing with individual LIPS assays using truncated GADA to improve specificity. Coeliac disease screening used a tissue transglutaminase IgA (TGA-IgA) LIPS assay. Capillary-venous sample concordance and assay format comparisons validated the methodology. RESULTS: Among 1454 individuals without known diabetes, islet autoantibody prevalence was 2.3% (95% CI 1.6, 3.2), with 70.6% having single autoantibodies and 29.4% having multiple autoantibodies. Among 73 individuals with type 2 diabetes, 9.6% (95% CI 3.9, 18.8) were islet autoantibody-positive. TGA-IgA prevalence was 3.5% (95% CI 2.7, 4.6) overall, with 3.2% (95% CI 2.3, 4.2) newly identified positivity among those without known coeliac disease. Capillary-venous sample concordance was high (85-95% across autoantibodies), increasing with antibody level from 66.7% to 100% across terciles. Venous LIPS to bridge-ELISA concordance ranged from 50% for GADA to 90% for other autoantibodies, with low-affinity GADA partially accounting for discrepancies. Islet autoantibody-positive individuals >15 years (measured by 3-screen solid-phase capture LIPS) had significantly higher median antibody levels than those ≤15 years (53.5 vs 19.3 arbitrary units, p=0.006). Coeliac disease autoantibody prevalence declined markedly with age from 9.1% (≤15 years) to 0.6% (>75 years) (p