Peptide serum markers in islet autoantibody-positive children

被引:22
作者
von Toerne, Christine [1 ]
Laimighofer, Michael [2 ,3 ]
Achenbach, Peter [4 ,5 ,6 ]
Beyerlein, Andreas [4 ,5 ]
Gala, Tonia de las Heras [7 ,8 ]
Krumsiek, Jan [2 ,7 ]
Theis, Fabian J. [2 ,3 ]
Ziegler, Anette G. [4 ,5 ,6 ]
Hauck, Stefanie M. [1 ]
机构
[1] Helmholtz Zentrum Munchen, Res Unit Prot Sci, German Res Ctr Environm Hlth GmbH, Ingolstadter Landstr 1, D-85764 Munich, Germany
[2] Helmholtz Zentrum Munchyen, German Res Ctr Environm Hlth GmbH, Inst Computat Biol, Neuherberg, Germany
[3] Tech Univ Munich, Dept Math, Garching, Germany
[4] Helmholtz Zentrum Munchen, Diabet Res Inst, German Res Ctr Environm Hlth GmbH, Ingolstadter Landstr 1, D-85764 Munich, Germany
[5] Tech Univ Munich, Forschergrp Diabet, Klinikum Rechts Isar, Munich, Germany
[6] Forschergrp Diabet eV, Neuherberg, Germany
[7] German Ctr Diabet Res DZD, Neuherberg, Germany
[8] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth GmbH, Inst Epidemiol 2, Neuherberg, Germany
关键词
Autoantibody-positive; Autoimmunity; BABYDIAB/BABYDIET; LC-MS/MS; Progression time; Risk score; Selected reactionmonitoring; Targeted proteomic; Type; 1; diabetes; ANTIBODY STANDARDIZATION PROGRAM; APOLIPOPROTEIN M; INCREASED RISK; DIABETES RISK; TYPE-1; AUTOIMMUNITY; PROTEOMICS; PLASMA; ASSAYS; CERULOPLASMIN;
D O I
10.1007/s00125-016-4150-x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Aims/hypothesis We sought to identify minimal sets of serum peptide signatures as markers for islet autoimmunity and predictors of progression rates to clinical type 1 diabetes in a case-control study. Methods A double cross-validation approach was applied to first prioritise peptides from a shotgun proteomic approach in 45 islet autoantibody-positive and -negative children from the BABYDIAB/BABYDIET birth cohorts. Targeted proteomics for 82 discriminating peptides were then applied to samples from another 140 children from these cohorts. Results A total of 41 peptides (26 proteins) enriched for the functional category lipid metabolism were significantly different between islet autoantibody-positive and autoantibody-negative children. Two peptides (from apolipoprotein M and apolipoprotein C-IV) were sufficient to discriminate autoantibody-positive from autoantibody-negative children. Hepatocyte growth factor activator, complement factor H, ceruloplasmin and age predicted progression time to type 1 diabetes with a significant improvement compared with age alone. Conclusion/interpretation Distinct peptide signatures indicate islet autoimmunity prior to the clinical manifestation of type 1 diabetes and enable refined staging of the presymptomatic disease period.
引用
收藏
页码:287 / 295
页数:9
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