Serum Proteomes Distinguish Children Developing Type 1 Diabetes in a Cohort With HLA-Conferred Susceptibility

被引：43

作者：

Moulder, Robert ^{[1
]}

Bhosale, Santosh D. ^{[1
]}

Erkkila, Timo ^{[2
]}

Laajala, Essi ^{[1
]}

Salmi, Jussi ^{[1
]}

Nguyen, Elizabeth V. ^{[1
]}

Kallionpaa, Henna ^{[1
]}

Mykkanen, Juha ^{[3
,4
]}

Vaha-Makila, Mari ^{[3
,4
]}

Hyoty, Heikki ^{[5
,6
]}

Veijola, Riitta ^{[7
,8
]}

Ilonen, Jorma ^{[9
,10
]}

Simell, Tuula ^{[3
,4
]}

Toppari, Jorma ^{[3
,4
,11
]}

Knip, Mikael ^{[12
,13
,14
,15
,16
]}

Goodlett, David R. ^{[1
,17
]}

Lahdesmaki, Harri ^{[1
,2
]}

Simell, Olli ^{[3
,4
]}

Lahesmaa, Riitta ^{[1
]}

机构：

[1] Univ Turku, Turku Ctr Biotechnol, Turku, Finland

[2] Aalto Univ, Sch Sci, Dept Informat & Comp Sci, Espoo, Finland

[3] Univ Turku, Dept Pediat, Turku, Finland

[4] Turku Univ Hosp, Dept Pediat, FIN-20520 Turku, Finland

[5] Univ Tampere, Sch Med, FIN-33101 Tampere, Finland

[6] Pirkanmaa Hosp Dist, Fimlab Labs, Tampere, Finland

[7] Univ Oulu, Oulu, Finland

[8] Oulu Univ Hosp, Dept Pediat, Oulu, Finland

[9] Univ Eastern Finland, Dept Clin Microbiol, Kuopio, Finland

[10] Univ Turku, Immunogenet Lab, Turku, Finland

[11] Univ Turku, Dept Physiol, Turku, Finland

[12] Univ Helsinki, Childrens Hosp, Helsinki, Finland

[13] Univ Helsinki, Cent Hosp, Helsinki, Finland

[14] Univ Helsinki, Res Program, Diabet & Obes, Helsinki, Finland

[15] Tampere Univ Hosp, Dept Pediat, Tampere, Finland

[16] Folkhalsan Res Inst, Helsinki, Finland

[17] Univ Maryland, Dept Pharmaceut Sci, Baltimore, MD 21201 USA

来源：

DIABETES | 2015年 / 64卷 / 06期

基金：

芬兰科学院;

关键词：

BETA-CELL AUTOIMMUNITY; QUANTITATIVE PROTEOMICS; ISLET AUTOIMMUNITY; LABEL-FREE; DISCOVERY; ITRAQ; DYSREGULATION; PREDICTION; MASS; SEROCONVERSION;

D O I：

10.2337/db14-0983

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

We determined longitudinal serum proteomics profiles from children with HLA-conferred diabetes susceptibility to identify changes that could be detected before seroconversion and positivity for disease-associated autoantibodies. Comparisons were made between children who seroconverted and progressed to type 1 diabetes (progressors) and those who remained autoantibody negative, matched by age, sex, sample periodicity, and risk group. The samples represented the prediabetic period and ranged from the age of 3 months to 12 years. After immunoaffinity depletion of the most abundant serum proteins, isobaric tags for relative and absolute quantification were used for sample labeling. Quantitative proteomic profiles were then measured for 13 case-control pairs by high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS). Additionally, a label-free LC-MS/MS approach was used to analyze depleted sera from six case-control pairs. Importantly, differences in abundance of a set of proteins were consistently detected before the appearance of autoantibodies in the progressors. Based on top-scoring pairs analysis, classification of such progressors was observed with a high success rate. Overall, the data provide a reference of temporal changes in the serum proteome in healthy children and children progressing to type 1 diabetes, including new protein candidates, the levels of which change before clinical diagnosis.

引用

页码：2265 / 2278

页数：14

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