Targeted Analysis of Serum Proteins Encoded at Known Inflammatory Bowel Disease Risk Loci

Autor: Björn Forsström, Jochen M. Schwenk, Ferdinando Bonfiglio, Anna Reznichenko, Mauro D'Amato, Dirk Repsilber, Claudia Fredolini, Kristian Sandberg, Weronica E. Ek, Mun-Gwan Hong, Eni Andersson, Tahmina Akhter, Ghazaleh Assadi, Dario Greco, Kimi Drobin, Jonas Halfvarson, Mark Berner Hansen
Přispěvatelé: Institute of Biotechnology, Research Programs Unit, Helsinki University Hospital Area, Tampere University, BioMediTech
Jazyk: angličtina
Rok vydání: 2018
Předmět:
0301 basic medicine
AMINOPEPTIDASES
Male
Proteome
Infektionsmedicin
Proteomics
Inflammatory bowel disease
Cohort Studies
0302 clinical medicine
Crohn Disease
Immunology and Allergy
Child
Gastroenterology
1184 Genetics
developmental biology
physiology
ASSOCIATION
Blood Proteins
Middle Aged
Prognosis
Blood proteins
3. Good health
ULCERATIVE-COLITIS
Child
Preschool
PROTEOMICS
030211 gastroenterology & hepatology
Female
Antibody
Adult
Infectious Medicine
GENETICS
Adolescent
Original Basic Science Articles
Gastroenterology and Hepatology
Biology
3121 Internal medicine
digestive system
03 medical and health sciences
Young Adult
inflammatory bowel disease
medicine
Gastroenterologi
Humans
affinity proteomics
Colitis
Aged
RECEPTOR
Case-control study
LACC1
medicine.disease
digestive system diseases
030104 developmental biology
TISSUE
DISCOVERY
3121 General medicine
internal medicine and other clinical medicine
Case-Control Studies
Immunology
biology.protein
Colitis
Ulcerative
3111 Biomedicine
Biomarkers
Zdroj: Inflammatory Bowel Diseases
ISSN: 1536-4844
1078-0998
Popis: Background: Few studies have investigated the blood proteome of inflammatory bowel disease (IBD). We characterized the serum abundance of proteins encoded at 163 known IBD risk loci and tested these proteins for their biomarker discovery potential. Methods: Based on the Human Protein Atlas (HPA) antibody availability, 218 proteins from genes mapping at 163 IBD risk loci were selected. Targeted serum protein profiles from 49 Crohn’s disease (CD) patients, 51 ulcerative colitis (UC) patients, and 50 sex- and age-matched healthy individuals were obtained using multiplexed antibody suspension bead array assays. Differences in relative serum abundance levels between disease groups and controls were examined. Replication was attempted for CD-UC comparisons (including disease subtypes) by including 64 additional patients (33 CD and 31 UC). Antibodies targeting a potentially novel risk protein were validated by paired antibodies, Western blot, immuno-capture mass spectrometry, and epitope mapping. Results: By univariate analysis, 13 proteins mostly related to neutrophil, T-cell, and B-cell activation and function were differentially expressed in IBD patients vs healthy controls, 3 in CD patients vs healthy controls and 2 in UC patients vs healthy controls (q < 0.01). Multivariate analyses further differentiated disease groups from healthy controls and CD subtypes from UC (P < 0.05). Extended characterization of an antibody targeting a novel, discriminative serum marker, the laccase (multicopper oxidoreductase) domain containing 1 (LACC1) protein, provided evidence for antibody on-target specificity. Conclusions: Using affinity proteomics, we identified a set of IBD-associated serum proteins encoded at IBD risk loci. These candidate proteins hold the potential to be exploited as diagnostic biomarkers of IBD. Jochen M. Schwenk, Mauro D’Amato and Jonas Halfvarson contributed equally.
Databáze: OpenAIRE
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