| 1. |
- Drobin, Kimi, et al.
(författare)
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Targeted Analysis of Serum Proteins Encoded at Known Inflammatory Bowel Disease Risk Loci
- 2019
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Ingår i: Inflammatory Bowel Diseases. - : Oxford University Press. - 1078-0998 .- 1536-4844. ; 25:2, s. 306-316
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 2. |
- Ek, Weronica E, et al.
(författare)
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The history of genetics in inflammatory bowel disease
- 2014
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Ingår i: Annals of Gastroenterology. - Athens, Greece : Hellenic Society of Gastroenterology. - 1108-7471 .- 1792-7463. ; 27:4, s. 294-303
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Forskningsöversikt (refereegranskat)abstract
- The influence of genetics in the etiology of inflammatory bowel disease (IBD) was initially demonstrated by epidemiological data, including differences in prevalence among different ethnic groups, familial aggregation of IBD, concordance in twins, and association with genetic syndromes. These early observations paved the way to molecular genetics in IBD, and culminated in the identification of nucleotide-binding oligomerization domain containing 2 (NOD2) gene as an IBD risk gene in 2001. As in other complex diseases, the advent of Genome Wide Association studies has dramatically improved the resolution of the IBD genome and our understanding of the pathogenesis of IBD. However, the complexity of the genetic puzzle in IBD seems more pronounced today than ever previously. In total, 163 risk genes/loci have been identified, and the corresponding number of possible causal variants is challenging. The great majority of these loci are associated with both Crohn's disease and ulcerative colitis, suggesting that nearly all of the biological mechanisms involved in one disease play some role in the other. Interestingly, a large proportion of the IBD risk loci are also shared with other immune-mediated diseases, primary immunodeficiencies and mycobacterial diseases.
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