{"doi":"10.3390/diagnostics15131695","title":"A Comparative Evaluation of the Chemiluminescence Immunoassay and ELISA for the Detection of Islet Autoantibodies in Type 1 Diabetes","abstract":"<jats:p>Background: The early detection of type 1 diabetes (T1D) through screening for major islet autoantibodies is receiving increasing attention as a public health strategy, exemplified by the recent implementation of a pilot pediatric screening program in Italy. The transition from research-based screening to large-scale population initiatives needs automated and standardized assays that are capable of processing extensive sample volumes. Hence, this study aimed to evaluate the analytical performance and comparability of a fully automated chemiluminescence immunoassay (CLIA) compared to a conventional enzyme-linked immunosorbent assay (ELISA) for the detection of three classes of major islet antibodies—anti-GAD (GADA), anti-IA-2 (IA-2A), and anti-ZnT8 (ZnT8A). Methods: A total of 104 serum specimens were analyzed for each autoantibody using both ELISA (RSR and Medyzim, DYNES, DSX) and CLIA (MAGLUMI 800). Assay precision and linearity were assessed through intra-assay variability studies and dilution protocols. Methods agreement was evaluated with Passing–Bablok regression, Spearman’s correlation, Bland–Altman analysis, and Cohen’s kappa statistics. Results: The CLIA showed good precision and excellent linearity across clinically relevant concentration ranges of all islet antibodies. Correlation coefficients and categorical agreement between CLIA and ELISA were high (r &gt; 0.96 and Cohen’s kappa &gt;0.8 for all), with ZnT8A exhibiting the highest concordance. However, proportional biases were found, as CLIA systematically underestimated GADA and ZnT8A levels, while overestimated IA-2A compared to the ELISA. Conclusions: The CLIA displayed satisfactory precision and agreement with ELISA for GADA, IA-2A, and ZnT8A detection. Our findings support the use of these automated immunoassays in large-scale population initiatives for diagnosing T1D, but we also highlight the need for further efforts to achieve better inter-assay harmonization.</jats:p>","journal":"Diagnostics","year":2025,"id":603354,"datarank":0.24141568686511508,"base_score":1.6094379124341003,"endowment":1.6094379124341003,"self_citation_contribution":0.24141568686511508,"citation_network_contribution":0.0,"self_endowment_contribution":0.24141568686511508,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":750015,"name":"Claudia Piona","orcid":"0000-0001-5168-8317","position":1,"is_corresponding":false},{"id":1547776,"name":"Mariateresa Rizza","orcid":null,"position":2,"is_corresponding":false},{"id":1547777,"name":"Elena Tiziani","orcid":null,"position":3,"is_corresponding":false},{"id":1547778,"name":"Laura Pighi","orcid":null,"position":4,"is_corresponding":false},{"id":1547780,"name":"Elisa Morotti","orcid":null,"position":5,"is_corresponding":false},{"id":1544932,"name":"Gian Luca Salvagno","orcid":null,"position":6,"is_corresponding":false},{"id":1547781,"name":"Camilla Mattiuzzi","orcid":"0000-0002-5902-2525","position":7,"is_corresponding":false},{"id":568835,"name":"Claudio Maffeis","orcid":"0000-0002-3563-4404","position":8,"is_corresponding":false},{"id":104069,"name":"Giuseppe Lippi","orcid":"0000-0001-9523-9054","position":9,"is_corresponding":false},{"id":1547775,"name":"Elisa Danese","orcid":"0000-0002-2454-0410","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"A Comparative Evaluation of the Chemiluminescence Immunoassay and ELISA for the Detection of Islet Autoantibodies in Type 1 Diabetes","abstract":"<jats:p>Background: The early detection of type 1 diabetes (T1D) through screening for major islet autoantibodies is receiving increasing attention as a public health strategy, exemplified by the recent implementation of a pilot pediatric screening program in Italy. The transition from research-based screening to large-scale population initiatives needs automated and standardized assays that are capable of processing extensive sample volumes. Hence, this study aimed to evaluate the analytical performance and comparability of a fully automated chemiluminescence immunoassay (CLIA) compared to a conventional enzyme-linked immunosorbent assay (ELISA) for the detection of three classes of major islet antibodies—anti-GAD (GADA), anti-IA-2 (IA-2A), and anti-ZnT8 (ZnT8A). Methods: A total of 104 serum specimens were analyzed for each autoantibody using both ELISA (RSR and Medyzim, DYNES, DSX) and CLIA (MAGLUMI 800). Assay precision and linearity were assessed through intra-assay variability studies and dilution protocols. Methods agreement was evaluated with Passing–Bablok regression, Spearman’s correlation, Bland–Altman analysis, and Cohen’s kappa statistics. Results: The CLIA showed good precision and excellent linearity across clinically relevant concentration ranges of all islet antibodies. Correlation coefficients and categorical agreement between CLIA and ELISA were high (r &gt; 0.96 and Cohen’s kappa &gt;0.8 for all), with ZnT8A exhibiting the highest concordance. However, proportional biases were found, as CLIA systematically underestimated GADA and ZnT8A levels, while overestimated IA-2A compared to the ELISA. Conclusions: The CLIA displayed satisfactory precision and agreement with ELISA for GADA, IA-2A, and ZnT8A detection. Our findings support the use of these automated immunoassays in large-scale population initiatives for diagnosing T1D, but we also highlight the need for further efforts to achieve better inter-assay harmonization.</jats:p>","is_dataset_classified":null,"base_score":1.6094379124341003,"endowment":1.6094379124341003,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"40647694","pmcid":"PMC12249052","openalex_id":"https://openalex.org/W4412009415","authors":[],"funders":[],"total_grants":0,"fwci":3.9195,"citation_percentile":0.93595172,"influential_citations":0,"citation_trend":[{"year":2025,"count":2},{"year":2026,"count":2}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://www.mdpi.com/2075-4418/15/13/1695/pdf?version=1751521520","host_type":"journal"},{"url":"https://www.mdpi.com/2075-4418/15/13/1695/pdf?version=1751521520","host_type":"publisher"},{"url":"https://www.mdpi.com/2075-4418/15/13/1695/pdf","host_type":"publisher"},{"url":"https://doi.org/10.3390/diagnostics15131695","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/40647694","host_type":"repository"},{"url":"https://doaj.org/article/326e8e2223c2477ca76b04805e617353","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/12249052","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC12249052","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC12249052?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Diabetes and associated disorders","Pancreatic function and diabetes","Diabetes Management and Research"],"mesh_terms":[],"keywords":["Autoantibody","Immunoassay","Chemiluminescence","Islet","Type 1 diabetes","Chemiluminescent immunoassay","Medicine","Antibody","Chromatography","Diabetes mellitus","Internal medicine","Immunology","Chemistry","Endocrinology","ELISA","Type 1 diabetes mellitus","CLIA","Chemiluminescence immunoassay","Gada","Ia-2a","Islet Autoantibody","Znt8a"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"doi"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-29T21:42:49.475081Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}