Low TREM1 expression in whole blood predicts anti-TNF response in inflammatory bowel disease.
Adult
Antibodies, Monoclonal
/ therapeutic use
Biomarkers
Colitis, Ulcerative
/ blood
Crohn Disease
/ blood
Female
Gene Expression
Humans
Inflammatory Bowel Diseases
/ blood
Male
Middle Aged
Molecular Targeted Therapy
Nomograms
Prognosis
Treatment Outcome
Triggering Receptor Expressed on Myeloid Cells-1
/ blood
Tumor Necrosis Factor-alpha
/ antagonists & inhibitors
Adalimumab
Anti-TNF
Biomarker
Endoscopic remission
IBD
Infliximab
Personalised medicine
TREM1
Journal
EBioMedicine
ISSN: 2352-3964
Titre abrégé: EBioMedicine
Pays: Netherlands
ID NLM: 101647039
Informations de publication
Date de publication:
Feb 2019
Feb 2019
Historique:
received:
16
12
2018
revised:
04
01
2019
accepted:
11
01
2019
pubmed:
28
1
2019
medline:
27
6
2019
entrez:
28
1
2019
Statut:
ppublish
Résumé
With the changed therapeutic armamentarium for Crohn's disease (CD) and ulcerative colitis (UC), biomarkers predicting treatment response are urgently needed. We studied whole blood and mucosal expression of genes previously reported to predict outcome to anti-TNF therapy, and investigated if the signature was specific for anti-TNF agents. We prospectively included 54 active IBD patients (24CD, 30UC) initiating anti-TNF therapy, as well as 22 CD patients initiating ustekinumab and 51 patients initiating vedolizumab (25CD, 26UC). Whole blood expression of OSM, TREM1, TNF and TNFR2 was measured prior to start of therapy using qPCR, and mucosal gene expression in inflamed biopsies using RNA-sequencing. Response was defined as endoscopic remission (SES-CD ≤ 2 at week 24 for CD and Mayo endoscopic sub-score ≤ 1 at week 10 for UC). Baseline whole blood TREM1 was downregulated in future anti-TNF responders, both in UC (FC = 0.53, p = .001) and CD (FC = 0.66, p = .007), as well as in the complete cohort (FC = 0.67, p < .001). Receiver operator characteristic statistics showed an area under the curve (AUC) of 0.78 (p = .001). A similar accuracy could be achieved with mucosal TREM1 (AUC 0.77, p = .003), which outperformed the accuracy of serum TREM1 (AUC 0.58, p = .31). Although differentially expressed in tissue, OSM, TNF and TNFR2 were not differentially expressed in whole blood. The TREM1 predictive signal was anti-TNF specific, as no changes were seen in ustekinumab and vedolizumab treated patients. We identified low TREM-1 as a specific biomarker for anti-TNF induced endoscopic remission. These results can aid in the selection of therapy in biologic-naïve patients.
Sections du résumé
BACKGROUND
BACKGROUND
With the changed therapeutic armamentarium for Crohn's disease (CD) and ulcerative colitis (UC), biomarkers predicting treatment response are urgently needed. We studied whole blood and mucosal expression of genes previously reported to predict outcome to anti-TNF therapy, and investigated if the signature was specific for anti-TNF agents.
METHODS
METHODS
We prospectively included 54 active IBD patients (24CD, 30UC) initiating anti-TNF therapy, as well as 22 CD patients initiating ustekinumab and 51 patients initiating vedolizumab (25CD, 26UC). Whole blood expression of OSM, TREM1, TNF and TNFR2 was measured prior to start of therapy using qPCR, and mucosal gene expression in inflamed biopsies using RNA-sequencing. Response was defined as endoscopic remission (SES-CD ≤ 2 at week 24 for CD and Mayo endoscopic sub-score ≤ 1 at week 10 for UC).
FINDINGS
RESULTS
Baseline whole blood TREM1 was downregulated in future anti-TNF responders, both in UC (FC = 0.53, p = .001) and CD (FC = 0.66, p = .007), as well as in the complete cohort (FC = 0.67, p < .001). Receiver operator characteristic statistics showed an area under the curve (AUC) of 0.78 (p = .001). A similar accuracy could be achieved with mucosal TREM1 (AUC 0.77, p = .003), which outperformed the accuracy of serum TREM1 (AUC 0.58, p = .31). Although differentially expressed in tissue, OSM, TNF and TNFR2 were not differentially expressed in whole blood. The TREM1 predictive signal was anti-TNF specific, as no changes were seen in ustekinumab and vedolizumab treated patients.
INTERPRETATION
CONCLUSIONS
We identified low TREM-1 as a specific biomarker for anti-TNF induced endoscopic remission. These results can aid in the selection of therapy in biologic-naïve patients.
Identifiants
pubmed: 30685385
pii: S2352-3964(19)30032-5
doi: 10.1016/j.ebiom.2019.01.027
pmc: PMC6413341
pii:
doi:
Substances chimiques
Antibodies, Monoclonal
0
Biomarkers
0
TREM1 protein, human
0
Triggering Receptor Expressed on Myeloid Cells-1
0
Tumor Necrosis Factor-alpha
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
733-742Informations de copyright
Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.
Références
Mol Immunol. 2002 Mar;38(11):817-24
pubmed: 11922939
J Clin Invest. 2007 Oct;117(10):3097-106
pubmed: 17853946
Gut. 2009 Dec;58(12):1612-9
pubmed: 19700435
Inflamm Bowel Dis. 2010 Dec;16(12):2090-8
pubmed: 20848504
Am J Gastroenterol. 2011 Jul;106(7):1272-80
pubmed: 21448149
J Crohns Colitis. 2012 Oct;6(9):913-23
pubmed: 22410349
Gut. 2014 Jan;63(1):88-95
pubmed: 23974954
Dig Dis. 2014;32(4):351-9
pubmed: 24969279
Bioinformatics. 2015 Jan 15;31(2):166-9
pubmed: 25260700
Genome Biol. 2014;15(12):550
pubmed: 25516281
Nat Methods. 2015 Apr;12(4):357-60
pubmed: 25751142
PLoS One. 2015 May 21;10(5):e0127877
pubmed: 25996941
J Crohns Colitis. 2015 Dec;9(12):1079-87
pubmed: 26351381
J Crohns Colitis. 2016 Mar;10(3):323-9
pubmed: 26417049
J Immunol. 2015 Dec 15;195(12):5725-31
pubmed: 26561551
J Crohns Colitis. 2016 Aug;10(8):989-97
pubmed: 26896086
Inflamm Bowel Dis. 2016 Aug;22(8):1803-11
pubmed: 27243593
Gut. 2017 Dec;66(12):2063-2068
pubmed: 27590995
Mucosal Immunol. 2017 Jul;10(4):1021-1030
pubmed: 27966555
Nat Med. 2017 May;23(5):579-589
pubmed: 28368383
J Autoimmun. 2017 Dec;85:103-116
pubmed: 28711286
J Crohns Colitis. 2018 Jan 24;12(2):230-244
pubmed: 28961797
Therap Adv Gastroenterol. 2018 Jan 10;11:1756283X17745029
pubmed: 29383027
J Gastroenterol. 2018 May;53(5):585-590
pubmed: 29556726
Cell Mol Immunol. 2018 Mar 22;:null
pubmed: 29568119
Gut. 2019 Apr;68(4):604-614
pubmed: 29618496
Gut. 2018 May 30;:null
pubmed: 29848778
Gut. 2018 Jul 14;:null
pubmed: 30007919
J Crohns Colitis. 2019 Mar 26;13(3):273-284
pubmed: 30137278
Aliment Pharmacol Ther. 2019 Mar;49(5):572-581
pubmed: 30663072