Proteomic Technologies for the Discovery of Type 1 Diabetes Biomarkers

Zhi, Wenbo; Purohit, Sharad; Carey, Colleen; Wang, Meiyao; She, Jin Xiong

doi:10.1177/193229681000400431

Cited by 41 publications

(29 citation statements)

References 30 publications

(37 reference statements)

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“…The two dimensional liquid chromatography (2DLC) mass spectrometry platform has been widely used in the discovery of protein candidates that may serve as biomarkers (5). Prior to the MS analysis, serum samples have to be processed to reduce the dynamic range and enrich for low-abundance proteins (e.g.…”

Section: Type 1 Diabetes (T1d)mentioning

confidence: 99%

Discovery and Validation of Serum Protein Changes in Type 1 Diabetes Patients Using High Throughput Two Dimensional Liquid Chromatography-Mass Spectrometry and Immunoassays

Zhi

Sharma

Purohit

et al. 2011

Molecular & Cellular Proteomics

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Type 1 diabetes (T1D) is expected to cause significant changes in the serum proteome; however, few studies have systematically assessed the proteomic profile change associated with the disease. In this study, a semiquantitative spectral counting-based two dimensional liquid chromatography mass spectrometry platform was used to analyze serum samples from T1D patients and controls. In this discovery phase, significant differences were found for 21 serum proteins implicated in inflammation, oxidation, metabolic regulation, and autoimmunity. To assess the validity of these findings, six candidate proteins including adiponectin, insulin-like growth factor binding protein 2, serum amyloid protein A, C-reactive protein, myeloperoxidase, and transforming growth factor beta induced were selected for subsequent immune assays for 1139 T1D patients and 848 controls. A series of statistical analyses using cases and controls matched for age, sex, and genetic risk confirmed that T1D patients have significantly higher serum levels for four of the six proteins: adiponectin (odds ratio (OR) ‫؍‬ 1.95, p ‫؍‬ 10 ؊27 ), insulin-like growth factor binding protein 2 (OR ‫؍‬ 2.02, p < 10 ؊20 ), C-reactive protein (OR ‫؍‬ 1.13, p ‫؍‬ 0.007), serum amyloid protein A (OR ‫؍‬ 1.51, p < 10 ؊16 ); whereas the serum levels were significantly lower in patients than controls for the two other proteins: transforming growth factor beta induced (OR ‫؍‬ 0.74, p < 10 ؊5 ) and myeloperoxidase (OR ‫؍‬ 0.51, p < 10 ؊41 ). Compared with subjects in the bottom quartile, subjects in the top quartile for adiponectin (OR ‫؍‬ 6.29, p < 10 ؊37 ), insulin-like growth factor binding protein 2 (OR ‫؍‬ 7.95, p < 10 ؊46 ), C-reactive protein (OR ‫؍‬ 1.38, p ‫؍‬ 0.025), serum amyloid protein A (OR ‫؍‬ 3.36, p < 10 ؊16 ) had the highest risk of T1D, whereas subjects in the top quartile of transforming growth factor beta induced (OR ‫؍‬ 0.41, p < 10 ؊11 ) and myeloperoxidase (OR ‫؍‬ 0.10, p < 10 ؊43

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Section: Type 1 Diabetes (T1d)mentioning

confidence: 99%

Discovery and Validation of Serum Protein Changes in Type 1 Diabetes Patients Using High Throughput Two Dimensional Liquid Chromatography-Mass Spectrometry and Immunoassays

Zhi

Sharma

Purohit

et al. 2011

Molecular & Cellular Proteomics

Self Cite

View full text Add to dashboard Cite

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“…Proteomic analyses in the study of type 1 diabetes has been previously reviewed (2) and applied in studies addressing differences in the sera of patients with diabetes and subjects without diabetes (3)(4)(5). Zhang et al (5) compared protein levels in plasma from patients with type 1 diabetes and healthy subjects, observing significant differences in the abundance of 24 proteins.…”

mentioning

confidence: 99%

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

et al. 2015

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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.

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“…Changes of physiological conditions are often reflected by alterations in protein expression and/or metabolism (18 -20). Shotgun quantitative proteomics, which systematically identifies and quantifies proteins at a proteome-wide scale, has emerged as a novel and powerful methodology for disease-related biomarker discovery (21). However, this approach has yet to be widely applied to bone biology.…”

mentioning

confidence: 99%

Peripheral Blood Monocyte-expressed ANXA2 Gene is Involved in Pathogenesis of Osteoporosis in Humans

Dèng

Lei

Zhang

et al. 2011

Molecular & Cellular Proteomics

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Low bone mineral density (BMD) is a risk factor of osteoporosis and has strong genetic determination. Genes influencing BMD and fundamental mechanisms leading to osteoporosis have yet to be fully determined. Peripheral blood monocytes (PBM) are potential osteoclast precursors, which could access to bone resorption surfaces and differentiate into osteoclasts to resorb bone. Herein, we attempted to identify osteoporosis susceptibility gene(s) and characterize their function(s), through an initial proteomics discovery study on PBM in vivo, and multiscale validation studies in vivo and in vitro. Utilizing the quantitative proteomics methodology LC-nano-ESI-MS E , we discovered that a novel protein, i.e. ANXA2, was up-regulated twofold in PBM in vivo in Caucasians with extremely low BMD (cases) versus those with extremely high BMD (controls) (n ‫؍‬ 28, p < 0.05). ANXA2 gene up-regulation in low BMD subjects was replicated at the mRNA level in PBM in vivo in a second and independent casecontrol sample (n ‫؍‬ 80, p < 0.05). At the DNA level, we found that SNPs in the ANXA2 gene were associated with BMD variation in a 3 rd and independent case-control sample (n ‫؍‬ 44, p < 0.05), as well as in a random population sample (n ‫؍‬ 997, p < 0.05). The above integrative evidence strongly supports the concept that ANXA2 is involved in the pathogenesis of osteoporosis in humans. Through a follow-up cellular functional study, we found that ANXA2 protein significantly promoted monocyte migration across an endothelial barrier in vitro (p < 0.001). Thus, elevated ANXA2 protein expression level, as detected in low BMD subjects, probably stimulates more PBM migration through the blood vessel walls to bone resorption surfaces in vivo, where they differentiate into higher number of osteoclasts and resorb bone at higher rates, thereby decreasing BMD. In conclusion, this study identified a novel osteoporosis susceptibility gene ANXA2, and suggested a novel pathophysiological mechanism, mediated by

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Proteomic Technologies for the Discovery of Type 1 Diabetes Biomarkers

Cited by 41 publications

References 30 publications

Discovery and Validation of Serum Protein Changes in Type 1 Diabetes Patients Using High Throughput Two Dimensional Liquid Chromatography-Mass Spectrometry and Immunoassays

Discovery and Validation of Serum Protein Changes in Type 1 Diabetes Patients Using High Throughput Two Dimensional Liquid Chromatography-Mass Spectrometry and Immunoassays

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

Peripheral Blood Monocyte-expressed ANXA2 Gene is Involved in Pathogenesis of Osteoporosis in Humans

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