Dataset Information

Low mass blood peptides discriminative of IBD severity

ABSTRACT: The enriched low mass proteome is unexplored as a source of differentiators for diagnosing and monitoring Inflammatory Bowel Disease (IBD) activity, less invasively than colonoscopy and histopathology. Differences in the enriched low mass plasma proteome (<25kDa) were assessed by label-free quantitative mass-spectrometry. A panel of marker candidates were progressed to validation phase and ‘Tier-2’ FDA-level validated quantitative assay. Proteins important in maintaining gut barrier function and homeostasis at the epithelial interface have been quantitated by Multiple Reaction Monitoring (MRM) in plasma and serum including both inflammatory rheumatoid arthritis controls (RA) and non-inflammatory healthy controls (C), ulcerative colitis (UC) and crohn’s disease (CD) patients. Detection by immunoblot confirmed presence at the protein level in serum. Correlation analysis and receiver operator characteristics were used to report the sensitivity and specificity. Five peptides discriminating IBD activity and severity had very little-to-no correlation to Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), white cell or platelet counts. Three of these peptides were found to be binding partners to SPP24 protein alongside other known matrix proteins. These Proteins have the potentially improve effective diagnosis and evaluate IBD activity, reducing the need for more invasive techniques.

INSTRUMENT(S): LTQ FT

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood

DISEASE(S): Crohn's Colitis

SUBMITTER: Valerie Wasinger

LAB HEAD: Valerie Wasinger

PROVIDER: PXD002821 | Pride | 2015-11-06

REPOSITORIES: Pride

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Publications

Reverse-polynomial dilution calibration methodology extends lower limit of quantification and reduces relative residual error in targeted peptide measurements in blood plasma.

Yau Yunki Y YY Duo Xizi X Leong Rupert W L RW Wasinger Valerie C VC

Molecular & cellular proteomics : MCP 20141209 2

Matrix effect is the alteration of an analyte's concentration-signal response caused by co-existing ion components. With electrospray ionization (ESI), matrix effects are believed to be a function of the relative concentrations, ionization efficiency, and solvation energies of the analytes within the electrospray ionization droplet. For biological matrices such as plasma, the interactions between droplet components is immensely complex and the effect on analyte signal response not well elucidate ...[more]

PMID: 25492093

Publication: 1/2

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Project description:Background. Chronic renal failure is characterized by progressive renal scarring and accelerated cardiovascular disease. In animal models, this is thought to be due to non-dialyzable uremic toxins M-bM-^@M-^S small, protein-bound molecules normally secreted via Organic Anion Transporters (OATs) in the proximal renal tubule,rather than filtered at the glomerulus. The best studied of these is indoxyl sulfate (IS). Methods. We examined global gene expression responses in cultured normal human renal tubular cells incubated with control plasma (n=5) or pre- and post-dialysis uremic plasma (n=10). Results. GeneSpring analysis of microarrays revealed significantly altered expression of 2016 genes. The expression of 537 genes M-bM-^@M-^\normalizedM-bM-^@M-^] in post-dialysis plasma, suggesting removal of M-bM-^@M-^\low molecular weight uremic toxinsM-bM-^@M-^] by dialysis. The expression of the majority of dysregulated genes (1479) was not normalized in post-dialysis plasma. These likely represent the effects of substances not effectively removed by dialysis (M-bM-^@M-^\protein-bound uremic toxinsM-bM-^@M-^]). Addition of indoxyl sulfateto control plasma simulated most effects (81.1%) of uremic plasma, while the addition of probenecid, an OAT inhibitor, to uremic plasma reversed most changes in gene expression. Analysis of molecular programs with the Gene Set Enrichment Analysis and the DAVID database revealed patterns common to indoxyl sulfate-treated control plasma, pre-dialysis, and post-dialysis uremic plasma. These included increased cell cycle, pro-inflammatory, and pro-fibrotic molecular programs, particularly genes in the TGF-M-NM-2 pathway. Conclusion: These findings provide insight into the role of non-dialyzable, protein-bound uremic toxins in the pathogenesis of renal scarring and uremic vasculopathy. The GSEA patterns confirm that inflammatory and fibrotic programs are active. Transcriptomic remodeling in response to external stimulus RNA from non-immortalized cultured renal cortical cells incubated with plasma samples from 5 controls, 10 uremics pre-dialysis, 10 uremics post-dialysis, 5 controls with indoxyl sulfate added, 5 uremics pre-dialysis with probenecid added, 5 uremics post-dialysis with indoxyl sulfate added

			Action	DRS
	090715_Tosylexperiment.mgf	Mgf
	250615_peptideMAGbead.htm	Other
	CD_A_F5.RAW	Raw
	CD_B_F5.RAW	Raw
	CD_C1_F5_LL.RAW	Raw