Plasma protein biomarkers predict both the development of persistent autoantibodies and type 1 diabetes 6 months prior to the onset of autoimmunity: the TEDDY Study
Plasma protein biomarkers predict both the development of persistent autoantibodies and type 1 diabetes 6 months prior to the onset of autoimmunity: the TEDDY Study
Abstract Type 1 diabetes (T1D) results from an autoimmune destruction of pancreatic β cells. A significant gap in understanding the disease cause is the lack of predictive biomarkers for each of its developmental stages. Here, we conducted a blinded, two-phase case-control plasma proteomics analysis of children enrolled in the TEDDY study to identify biomarkers predictive of autoimmunity and T1D development. First, we performed untargeted proteomics analyses of 2,252 samples from 184 individuals and identified 376 regulated proteins. Complement/coagulation, inflammatory signaling and metabolic proteins were regulated even prior to autoimmunity onset. Extracellular matrix proteins and antigen presentation were differentially regulated in individuals with autoimmunity who progressed to T1D versus those who maintained normoglycemia. We then performed targeted proteomics measurements of 167 proteins in 6,426 samples from 990 individuals and validated 83 biomarkers. A machine learning analysis predicted both the development of persistent autoantibodies and T1D onset 6 months before autoimmunity initiation, with an area under the receiver operating characteristic curve of 0.871 and 0.918, respectively. Our study identified and validated biomarkers highlighting pathways affected in different stages of T1D development.
Nakayasu Ernesto S.、Metz Thomas O.、Schepmoes Athena A.、Bramer Lisa M.、Lernmark ?ke、Hagopian William、Akolkar Beena、Smith Richard D.、Piehowski Paul D.、Engel Dave W.、Orton Daniel J.、Frohnert Brigitte I.、Ziegler Anette-G.、Gritsenko Marina A.、Ansong Charles、Sechi Salvatore、Qian Wei-Jun、Webb-Robertson Bobbie-Jo M.、Stanfill Bryan A.、Clauss Therese R.、Moore Ronald J.、Rewers Marian J.、Fillmore Thomas L.、Gao Yuqian、Toppari Jorma
Biological Sciences Division, Pacific Northwest National LaboratoryBiological Sciences Division, Pacific Northwest National LaboratoryBiological Sciences Division, Pacific Northwest National LaboratoryBiological Sciences Division, Pacific Northwest National LaboratoryUnit for Diabetes and Celiac Disease, Wallenberg/CRC, Department of Clinical Sciences, Lund University/CRC, Sk?ne University Hospital SUSPacific Northwest Diabetes Research InstituteNational Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of HealthBiological Sciences Division, Pacific Northwest National LaboratoryEnvironmental and Molecular Sciences DivisionComputational Analytics Division, Pacific Northwest National LaboratoryBiological Sciences Division, Pacific Northwest National LaboratoryBarbara Davis Center for Diabetes, University of ColoradoInstitute of Diabetes Research, Helmholtz Zentrum M¨1nchen Forschergruppe Diabetes, Technical University of Munich Forschergruppe Diabetes e.V. at Helmholtz Zentrum M¨1nchenBiological Sciences Division, Pacific Northwest National LaboratoryBiological Sciences Division, Pacific Northwest National LaboratoryNational Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of HealthBiological Sciences Division, Pacific Northwest National LaboratoryBiological Sciences Division, Pacific Northwest National LaboratoryComputational Analytics Division, Pacific Northwest National LaboratoryBiological Sciences Division, Pacific Northwest National LaboratoryBiological Sciences Division, Pacific Northwest National LaboratoryBarbara Davis Center for Diabetes, University of ColoradoBiological Sciences Division, Pacific Northwest National LaboratoryBiological Sciences Division, Pacific Northwest National LaboratoryDepartment of Pediatrics, Turku University Hospital Institute of Biomedicine, Research Centre for Integrative Physiology and Pharmacology and Centre for Population Health Research, University of Turku
基础医学生物科学研究方法、生物科学研究技术医学研究方法
Type 1 diabetesbiomarkersplasma proteomicsautoimmune response
Nakayasu Ernesto S.,Metz Thomas O.,Schepmoes Athena A.,Bramer Lisa M.,Lernmark ?ke,Hagopian William,Akolkar Beena,Smith Richard D.,Piehowski Paul D.,Engel Dave W.,Orton Daniel J.,Frohnert Brigitte I.,Ziegler Anette-G.,Gritsenko Marina A.,Ansong Charles,Sechi Salvatore,Qian Wei-Jun,Webb-Robertson Bobbie-Jo M.,Stanfill Bryan A.,Clauss Therese R.,Moore Ronald J.,Rewers Marian J.,Fillmore Thomas L.,Gao Yuqian,Toppari Jorma.Plasma protein biomarkers predict both the development of persistent autoantibodies and type 1 diabetes 6 months prior to the onset of autoimmunity: the TEDDY Study[EB/OL].(2025-03-28)[2025-04-24].https://www.medrxiv.org/content/10.1101/2022.12.07.22283187.点此复制
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