Plasma protein biomarkers predict the development of persistent autoantibodies and type 1 diabetes 6 months prior to the onset of autoimmunity

Nakayasu, Ernesto S.; Bramer, Lisa M.; Ansong, Charles; Schepmoes, Athena A.; Fillmore, Thomas L.; Gritsenko, Marina A.; Clauss, Therese R.; Gao, Yuqian; Piehowski, Paul D.; Stanfill, Bryan A.; Engel, Dave W.; Orton, Daniel J.; Moore, Ronald J.; Qian, Wei-Jun; Sechi, Salvatore; Frohnert, Brigitte I.; Toppari, Jorma; Ziegler, Anette-G.; Lernmark, Åke; Hagopian, William; Akolkar, Beena; Smith, Richard D.; Rewers, Marian J.; Webb-Robertson, Bobbie-Jo M.; Metz, Thomas O.

doi:10.1016/j.xcrm.2023.101093

Title: Plasma protein biomarkers predict the development of persistent autoantibodies and type 1 diabetes 6 months prior to the onset of autoimmunity

Journal Article · Sat Jul 01 00:00:00 EDT 2023 · Cell Reports Medicine

DOI:https://doi.org/10.1016/j.xcrm.2023.101093· OSTI ID:1992402

; Bramer, Lisa M.; Ansong, Charles; Schepmoes, Athena A.; Fillmore, Thomas L.; Gritsenko, Marina A.; Clauss, Therese R.; Gao, Yuqian; Piehowski, Paul D.; Stanfill, Bryan A.; Engel, Dave W.; Orton, Daniel J.; Moore, Ronald J.; Qian, Wei-Jun; Sechi, Salvatore; Frohnert, Brigitte I.; Toppari, Jorma; Ziegler, Anette-G.; Lernmark, Åke; Hagopian, William more »

Type 1 diabetes (T1D) results from autoimmune destruction of ß cells. Insufficient availability of biomarkers represents a significant gap in understanding the disease cause and progression. We conduct a 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 versus 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. Furthermore, our study identifies and validates biomarkers, highlighting pathways affected during T1D development.

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Research Organization:: Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)

Sponsoring Organization:: USDOE; National Institutes of Health (NIH)

Contributing Organization:: The TEDDY Study Group

Grant/Contract Number:: AC05-76RLO01830; HHSN267200700014C; U01 DK124166; U01 DK128847; U01 DK63790; U01 DK63821; U01 DK63829; U01 DK63836; U01 DK63861; U01 DK63863; U01 DK63865; UC4 DK100238; UC4 DK106955; UC4 DK112243; UC4 DK117483; UC4 DK63821; UC4 DK63829; UC4 DK63836; UC4 DK63861; UC4 DK63863; UC4 DK63865; UC4 DK95300; AC05-76RL01830; P41GM103493

OSTI ID:: 1992402

Alternate ID(s):: OSTI ID: 2000673

Report Number(s):: PNNL-SA-137771; S2666379123002124; 101093; PII: S2666379123002124

Journal Information:: Cell Reports Medicine, Journal Name: Cell Reports Medicine Vol. 4 Journal Issue: 7; ISSN 2666-3791

Publisher:: ElsevierCopyright Statement

Country of Publication:: United States

Language:: English

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60 APPLIED LIFE SCIENCES
type 1 diabetes
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Title: Plasma protein biomarkers predict the development of persistent autoantibodies and type 1 diabetes 6 months prior to the onset of autoimmunity

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References (50)

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