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

Kimi Drobin, Ghazaleh Assadi, Mun Gwan Hong, Eni Andersson, Claudia Fredolini, Björn Forsström, Anna Reznichenko, Tahmina Akhter, Weronica E. Ek, Ferdinando Bonfiglio, Mark Berner Hansen, Kristian Sandberg, Dario Greco, Dirk Repsilber, Jochen M. Schwenk, Mauro D'Amato, Jonas Halfvarson

Research output: Contribution to journalArticleResearchpeer-review

1 Citation (Scopus)

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.

Original languageEnglish
Pages (from-to)306-316
Number of pages11
JournalInflammatory Bowel Diseases
Volume25
Issue number2
DOIs
Publication statusPublished - 10 Jan 2019
Externally publishedYes

Cite this

Drobin, K., Assadi, G., Hong, M. G., Andersson, E., Fredolini, C., Forsström, B., ... Halfvarson, J. (2019). Targeted Analysis of Serum Proteins Encoded at Known Inflammatory Bowel Disease Risk Loci. Inflammatory Bowel Diseases, 25(2), 306-316. https://doi.org/10.1093/ibd/izy326
Drobin, Kimi ; Assadi, Ghazaleh ; Hong, Mun Gwan ; Andersson, Eni ; Fredolini, Claudia ; Forsström, Björn ; Reznichenko, Anna ; Akhter, Tahmina ; Ek, Weronica E. ; Bonfiglio, Ferdinando ; Hansen, Mark Berner ; Sandberg, Kristian ; Greco, Dario ; Repsilber, Dirk ; Schwenk, Jochen M. ; D'Amato, Mauro ; Halfvarson, Jonas. / Targeted Analysis of Serum Proteins Encoded at Known Inflammatory Bowel Disease Risk Loci. In: Inflammatory Bowel Diseases. 2019 ; Vol. 25, No. 2. pp. 306-316.
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title = "Targeted Analysis of Serum Proteins Encoded at Known Inflammatory Bowel Disease Risk Loci",
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.",
author = "Kimi Drobin and Ghazaleh Assadi and Hong, {Mun Gwan} and Eni Andersson and Claudia Fredolini and Bj{\"o}rn Forsstr{\"o}m and Anna Reznichenko and Tahmina Akhter and Ek, {Weronica E.} and Ferdinando Bonfiglio and Hansen, {Mark Berner} and Kristian Sandberg and Dario Greco and Dirk Repsilber and Schwenk, {Jochen M.} and Mauro D'Amato and Jonas Halfvarson",
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Drobin, K, Assadi, G, Hong, MG, Andersson, E, Fredolini, C, Forsström, B, Reznichenko, A, Akhter, T, Ek, WE, Bonfiglio, F, Hansen, MB, Sandberg, K, Greco, D, Repsilber, D, Schwenk, JM, D'Amato, M & Halfvarson, J 2019, 'Targeted Analysis of Serum Proteins Encoded at Known Inflammatory Bowel Disease Risk Loci', Inflammatory Bowel Diseases, vol. 25, no. 2, pp. 306-316. https://doi.org/10.1093/ibd/izy326

Targeted Analysis of Serum Proteins Encoded at Known Inflammatory Bowel Disease Risk Loci. / Drobin, Kimi; Assadi, Ghazaleh; Hong, Mun Gwan; Andersson, Eni; Fredolini, Claudia; Forsström, Björn; Reznichenko, Anna; Akhter, Tahmina; Ek, Weronica E.; Bonfiglio, Ferdinando; Hansen, Mark Berner; Sandberg, Kristian; Greco, Dario; Repsilber, Dirk; Schwenk, Jochen M.; D'Amato, Mauro; Halfvarson, Jonas.

In: Inflammatory Bowel Diseases, Vol. 25, No. 2, 10.01.2019, p. 306-316.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Targeted Analysis of Serum Proteins Encoded at Known Inflammatory Bowel Disease Risk Loci

AU - Drobin, Kimi

AU - Assadi, Ghazaleh

AU - Hong, Mun Gwan

AU - Andersson, Eni

AU - Fredolini, Claudia

AU - Forsström, Björn

AU - Reznichenko, Anna

AU - Akhter, Tahmina

AU - Ek, Weronica E.

AU - Bonfiglio, Ferdinando

AU - Hansen, Mark Berner

AU - Sandberg, Kristian

AU - Greco, Dario

AU - Repsilber, Dirk

AU - Schwenk, Jochen M.

AU - D'Amato, Mauro

AU - Halfvarson, Jonas

PY - 2019/1/10

Y1 - 2019/1/10

N2 - 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.

AB - 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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Drobin K, Assadi G, Hong MG, Andersson E, Fredolini C, Forsström B et al. Targeted Analysis of Serum Proteins Encoded at Known Inflammatory Bowel Disease Risk Loci. Inflammatory Bowel Diseases. 2019 Jan 10;25(2):306-316. https://doi.org/10.1093/ibd/izy326