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

被引：22

作者：

Nakayasu, Ernesto S. ^{[1
]}

Bramer, Lisa M. ^{[1
]}

Ansong, Charles ^{[1
]}

Schepmoes, Athena A. ^{[1
]}

Fillmore, Thomas L. ^{[1
]}

Gritsenko, Marina A. ^{[1
]}

Clauss, Therese R. ^{[1
]}

Gao, Yuqian ^{[1
]}

Piehowski, Paul D. ^{[2
]}

Stanfill, Bryan A. ^{[3
]}

Engel, Dave W. ^{[3
]}

Orton, Daniel J. ^{[1
]}

Moore, Ronald J. ^{[1
]}

Qian, Wei-Jun ^{[1
]}

Sechi, Salvatore ^{[4
]}

Frohnert, Brigitte I. ^{[5
]}

Toppari, Jorma ^{[6
,7
,8
]}

Ziegler, Anette-G. ^{[9
,10
,11
]}

Lernmark, Ake ^{[12
]}

Hagopian, William ^{[13
]}

Akolkar, Beena ^{[4
]}

Smith, Richard D. ^{[1
]}

Rewers, Marian J. ^{[5
]}

Webb-Robertson, Bobbie-Jo M. ^{[1
]}

Metz, Thomas O. ^{[1
]}

机构：

[1] Pacific Northwest Natl Lab, Biol Sci Div, Richland, WA 99354 USA

[2] Pacific Northwest Natl Lab, Environm & Mol Sci Div, Richland, WA USA

[3] Pacific Northwest Natl Lab, Computat Analyt Div, Richland, WA USA

[4] NIH, Natl Inst Diabet & Digest & Kidney Dis, Bethesda, MD USA

[5] Univ Colorado, Barbara Davis Ctr Diabet, Aurora, CO USA

[6] Turku Univ Hosp, Dept Pediat, Turku, Finland

[7] Univ Turku, Inst Biomed, Res Ctr Integrat Physiol & Pharmacol, Turku, Finland

[8] Univ Turku, Ctr Populat Hlth Res, Turku, Finland

[9] Helmholtz Zentrum Munchen, Inst Diabet Res, Munich, Germany

[10] Tech Univ Munich, Klinikum Rechts Isar, Forschergruppe Diabet, Munich, Germany

[11] Helmholtz Zentrum Munchen, Forschergruppe Diabet, Munich, Germany

[12] Lund Univ CRS, Skane Univ Hosp SUS, Dept Clin Sci, Unit Diabet & Celiac Dis,Wallenberg CRC, S-21428 Malmo, Sweden

[13] Pacific Northwest Diabet Res Inst, Seattle, WA USA

来源：

CELL REPORTS MEDICINE | 2023年 / 4卷 / 07期

关键词：

SOFTWARE TOOL; DISCOVERY; QUANTIFICATION; CHILDREN; COHORT;

D O I：

10.1016/j.xcrm.2023.101093

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Type 1 diabetes (T1D) results from autoimmune destruction of b cells. Insufficient availability of biomarkers represents a significant gap in understanding the disease cause and progression. We conduct blinded, twophase 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.

引用

页数：18

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