Introduction and Objective: PCR in T1D reflects transient recovery of β-cell function and immunoregulation early after disease onset. Methods: We isolated EVs from plasma of adolescents (12-18 years) with new-onset T1D at baseline, 3 months or during PCR and 6 months and matched healthy volunteers (HV) at baseline (N=10/group). EVs were characterized by nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM). EV proteins were measured using SomaScan 11K technology. Differential abundance (DA) was tested using mixed-effects models for repeated measures (MMRM). Classification models were generated using Random Forest (RF) with adaptive backward-elimination. Results: Four out of 10 participants with T1D achieved PCR. NTA and TEM confirmed vesicular size and morphology consistent with EVs. MMRM identified sets of DA EV proteins across clinical stages. Pancreas-specific protein, PRSS1 and IgA heavy chain (IGHA1/2) were altered between T1D and HV. PNLIP lipase and IGHA1/2 were elevated in adolescents without PCR. FcγRIIIa was elevated in T1D with PCR.(Fig) The RF classification model achieved high performance (ROC-AUC=0.96, accuracy=0.9) in distinguishing remission vs. non-remission and controls. Conclusion: EV proteomics can predict PCR in new-onset T1D, with pancreas- and immune-derived signatures linked to remission, supporting development of standardized assays to stratify patients for immune therapies Disclosure A. Bilal: None. Y.O. Nunez Lopez: None. A. Petrilli: None. K.M. Reddy: None. K. Grench: None. J. Cruz: Other - Certified Insulin Pump Trainer; Current; Omnipod, Tandem Diabetes Care, Inc., Beta Bionics, Inc. K.A. Irizarry: None. R. Pratley: Consultant; Current; Lilly USA LLC. Research Support; Current; National Institutes of Health, Novo Nordisk. Speaker's Bureau; Current; Novo Nordisk. Other - Consulting: Thru 12/31/2023 payment directed to Dr. Pratley's employer; as of 1/1/2024 payment directed to Dr. Pratley personally.; Current; Novo Nordisk. Consultant; Current; Pfizer Inc., Recordati Rare Diseases Inc., Regeneron Pharmaceuticals Inc., Response Pharmaceuticals, Rona Therapeutics Ltd. Research Support; Current; Sanofi. Consultant; Current; Scholar Rock Inc. Other - Consulting: Thru 12/31/2023 payment directed to Dr. Pratley's employer; as of 1/1/2024 payment directed to Dr. Pratley personally.; Current; Sun Pharmaceutical Industries Ltd. Consultant; Current; Third Rock Ventures, Verdiva Bio Dev Limited. Research Support; Current; AstraZeneca AB, Boehringer Ingelheim International GmbH, Abbott Laboratories. Consultant; Current; Abbott Laboratories, AbbVie Inc. Other - Consulting; stock options; Current; Altanine, Inc. Consultant; Current; Amgen Inc., AstraZeneca Pharmaceuticals LP. Other - Consulting: Thru 12/31/2023 payment directed to Dr. Pratley's employer; as of 1/1/2024 payment directed to Dr. Pratley personally.; Current; Bayer AG, Bayer HealthCare Pharmaceuticals Inc. Research Support; Current; Biomea Fusion. Consultant; Current; Boehringer Ingelheim Pharmaceuticals Inc., Carmot Therapeutics, Inc., Corcept Therapeutics. Research Support; Current; Dompé, Eli Lilly and Company. Other - Consulting: Thru 12/31/2023 payment directed to Dr. Pratley's employer; as of 1/1/2024 payment directed to Dr. Pratley personally.; Current; Eli Lilly and Company. Research Support; Current; Endogenex Inc. Other - Consulting: Thru 12/31/2023 payment directed to Dr. Pratley's employer; as of 1/1/2024 payment directed to Dr. Pratley personally.; Current; Endogenex Inc. Consultant; Current; F. Hoffmann-La Roche Ltd. Research Support; Current; Fractyl Health, Inc. Other - Consulting: Thru 12/31/2023 payment directed to Dr. Pratley's employer; as of 1/1/2024 payment directed to Dr. Pratley personally.; Ended; Gasherbrum Bio Inc., Genprex. Consultant; Current; Hanmi Pharm. Co., Ltd. Other - Consulting: Thru 12/31/2023 payment directed to Dr. Pratley's employer; as of 1/1/2024 payment directed to Dr. Pratley personally.; Ended; Intas Pharmaceuticals Ltd. Research Support; Current; Lexicon Pharmaceuticals, Inc. Consultant; Current; Lexicon Pharmaceuticals, Inc. Speaker's Bureau; Current; Lilly USA LLC. A. Casu: Research Support; Current; Enable Biosciences.
Bilal et al. (Fri,) studied this question.