Islet autoantibodies as precision diagnostic tools to characterize heterogeneity in type 1 diabetes: a systematic review

Jamie L. Felton, Maria J. Redondo, Richard A. Oram, Cate Speake, S. Alice Long, Suna Onengut-Gumuscu, Stephen S. Rich, Gabriela S. F. Monaco, Arianna Harris-Kawano, Dianna Perez, Zeb Saeed, Benjamin Hoag, Rashmi Jain, Carmella Evans-Molina, Linda A. DiMeglio, Heba M. Ismail, Dana Dabelea, Randi K. Johnson, Marzhan Urazbayeva, John M. WentworthKurt J. Grif, Emily K. Sims, Deirdre K. Tobias, Jordi Merino, Abrar Ahmad, Catherine Aiken, Jamie L. Benham, Dhanasekaran Bodhini, Amy L. Clark, Kevin Colclough, Rosa Corcoy, Sara J. Cromer, Daisy Duan, Jamie L. Felton, Ellen C. Francis, Pieter Gillard, Veronique Gingras, Romy Gaillard, Eram Haider, Alice Hughes, Jennifer M. Ikle, Laura M. Jacobsen, Anna R. Kahkoska, Anne Cathrine B. Thuesen, Mette K. Andersen, Christoffer Clemmensen, Torben Hansen, Mathias Ried-Larsen, John J. Nolan, Tina Vilsboll, ADA/EASD PMDI

Abstract

BACKGROUND: Islet autoantibodies form the foundation for type 1 diabetes (T1D) diagnosis and staging, but heterogeneity exists in T1D development and presentation. We hypothesized that autoantibodies can identify heterogeneity before, at, and after T1D diagnosis, and in response to disease-modifying therapies.

METHODS: We systematically reviewed PubMed and EMBASE databases (6/14/2022) assessing 10 years of original research examining relationships between autoantibodies and heterogeneity before, at, after diagnosis, and in response to disease-modifying therapies in individuals at-risk or within 1 year of T1D diagnosis. A critical appraisal checklist tool for cohort studies was modified and used for risk of bias assessment.

RESULTS: Here we show that 152 studies that met extraction criteria most commonly characterized heterogeneity before diagnosis (91/152). Autoantibody type/target was most frequently examined, followed by autoantibody number. Recurring themes included correlations of autoantibody number, type, and titers with progression, differing phenotypes based on order of autoantibody seroconversion, and interactions with age and genetics. Only 44% specifically described autoantibody assay standardization program participation.

CONCLUSIONS: Current evidence most strongly supports the application of autoantibody features to more precisely define T1D before diagnosis. Our findings support continued use of pre-clinical staging paradigms based on autoantibody number and suggest that additional autoantibody features, particularly in relation to age and genetic risk, could offer more precise stratification. To improve reproducibility and applicability of autoantibody-based precision medicine in T1D, we propose a methods checklist for islet autoantibody-based manuscripts which includes use of precision medicine MeSH terms and participation in autoantibody standardization workshops.

Original languageEnglish
Article number66
JournalCommunications medicine
Volume4
Issue number1
ISSN2730-664X
DOIs
Publication statusPublished - 6 Apr 2024

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