Plasma protein biomarkers predict the development of persistent autoantibodies and type 1 diabetes 6 months prior to the onset of autoimmunity
Year: 2023
Type: article
Study design: Observational Study
Abstract: Type 1 diabetes (T1D) results from autoimmune destruction of β cells. Insufficient availability of biomarkers represents a significant gap in understanding the disease cause and progression. We conduct blinded, two-phase case-control plasma proteomics on the TEDDY study to identify biomarkers predictive of T1D development. Untargeted proteomics of 2,252 samples from 184 individuals identify 376 regulated proteins, showing alteration of complement, inflammatory signaling, and metabolic proteins even prior to autoimmunity onset. Extracellular matrix and antigen presentation proteins are differentially regulated in individuals who progress to T1D vs. those that remain in autoimmunity. Targeted proteomics measurements of 167 proteins in 6,426 samples from 990 individuals validate 83 biomarkers. A machine learning analysis predicts if individuals would remain in autoimmunity or develop T1D 6 months before autoantibody appearance, with areas under receiver operating characteristic curves of 0.871 and 0.918, respectively. Our study identifies and validates biomarkers, highlighting pathways affected during T1D development.
Source: Cell Reports Medicine
Authors: Ernesto S. Nakayasu, Lisa M. Bramer, Charles Ansong, Athena A. Schepmoes, Thomas L. Fillmore, Marina A. Gritsenko, Therese R. Clauss, Yuqian Gao, Paul D. Piehowski, Bryan A. Stanfill, Dave W. Engel, Daniel J. Orton, Ronald J. Moore, Wei-Jun Qian, Salvatore Sechi, Brigitte I. Frohnert, Jorma Toppari, Anette-G. Ziegler, Åke Lernmark, William Hagopian, Beena Akolkar, Richard D. Smith, Marian J. Rewers, Bobbie-Jo M. Webb-Robertson, Thomas O. Metz
Institutions: Pacific Northwest National Laboratory, Environmental Molecular Sciences Laboratory, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, University of Colorado Health, University of Colorado Anschutz, University of Colorado Denver, University of Turku, Turku University Hospital, TUM Klinikum, Helmholtz Munich, Institute of Diabetes Research, Technical University of Munich, Lund University, Skåne University Hospital, Pacific Northwest Research Institute
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,460
Funders: U.S. Department of Energy, Battelle, University of Florida, University of Washington, Juvenile Diabetes Research Foundation United States of America, University of Colorado, Cedars-Sinai Medical Center, National Institutes of Health, Centers for Disease Control and Prevention, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Environmental Health Sciences, National Institute of Child Health and Human Development, U.S. National Library of Medicine, National Center for Advancing Translational Sciences, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Pacific Northwest National Laboratory
Awards: The Environmental Triggers of Diabetes (TEDDY), G1059221387, G1060215549, G1067467806, G1206190374, G1214947619, G1279015891, The Environmental Determinants of Diabetes in the Young (TEDDY) Study, G1321420742, Data Coordinating Center (DCC)for the Consortium for Identification of Environmen, G13592670, G1395047820, G1401262220, Establish a Data Coordinating Center (DCC) for the Consortium for Identification , The Environmental Determinants of Diabetes in the Young (TEDDY) Colorado Clinical, G1523804311, G1579044985, Follow-up on Subjects, Integrative Data Analysis and Measurement of Viral Antibodies in The Environmental Determinants of Diabetes in The Young Study (TEDDY), G1682253633, G1705418431, G1719220841, G1829819719, Limited Competition for the Continuation of Clinical Centers for the Environment, G2091679763, G218863751, G2202195204, G2207736455, Limited Competition for the Continuation of the clinical Centers for The Environmental Determinants of Diabetes in the Young (TEDDY) Study GERMANY_CLINICAL_CENTER, G2227242870, G2233603583, Multiplex Mass Spectrometric Protein Assays for Precise Monitoring of the Pathophysiology of Obesity, G2372824109, G2385510620, G2545975535, G2775016932, G2775970316, G2779258932, G2842904076, G2894924261, G2922493908, G2943411579, G2988778103, G3005245293, G3096162653, G3112565685, G314304557, The Study of Epigenetics and Infections in The Environmental Determinants of Diabetes in the Young (TEDDY), G3279866960, The Environmental Triggers of Diabetes (TEDDY) in Sweden, G3522037732, G3613198653, G3704177496, G3758850638, The TEDDY Study: Georgia/Florida Clinical Center, G3894417393, G3965408886, UF Clinical and Translational Science Award, G4122824941, G4242486629, G4308838457, G43781327, NIDDK Follow-up on Subjects and Immunological Assessments in The Environmental Determinants of Diabetes In The Young Study (TEDDY) (UC4), G4452749875, G4589687545, G4632327846, G4643748655, G4645440995, G4681373259, G4708980405, G4836116171, G4837472842, G4883047338, G4886555545, G4914435748, G4936100127, G495644668, G501612984, G5032027528, G5049334941, G50774395, G5115379558, G5170261597, G5201245022, G5211317889, The Environmental Determinants of Diabetes in the Young (TEDDY) Study, G5242222319, G5309571481, G5311253256, G5338665957, G5385447312, G5449366386, G5500374692, G5584869583, G5608475838, A Research Resource for Ultra-sensitive High Throughput Proteomics, G5726405315, G5827796785, The Environmental Determinants of Diabetes in Youth: Washington Clinical Center, The TEDDY Study: Georgia/Florida Clinical Center, G5939034817, G609917707, G6117615522, G6181459372, G6612027719, G668710393, G6735078940, G6813104048, G6815893093, THE TEDDY STUDY - COLORADO CLINICAL CENTER, G6917696290, G6983648412, G7274337890, G7306902319, The Environmental Determinants of Diabetes in the Young (TEDDY) Study, Washington Clinical Center, G7351559122, G739084109, G7397636282, G7580720332, G7646790264, G7727310496, G7747263455, G7824033549, G7974681761, Data Coordinating Center (DCC) for the Consortium for Identification of Environmental Determinants of Diabetes in the Young (TEDDY) Study, G818465332, G8193546616, Colorado Clinical and Transational Sciences Institute, G822356989, G8225611102, Data Coordinating Center, G832612391, G8334442907, G8453822046, G8516986467, G8728011626, G9000040612, G9000101750, G9000110373, G9000111155, G9000122217, Interferon Signaling in the T1D Islet Microenvironment, Limited Competition: Continued Follow-up of Subjects and Initiation of a Second Case-control Cohort in The Environmental Determinants of Diabetes in The Young Study (TEDDY), Alternative RNA splicing events contribute to the onset of islet dysfunction in T1D, G938880006, G954811561
OpenAlex ID: W4382726128