TY - JOUR

T1 - Estimating tissue-specific TNF mRNA levels prior to anti-TNFα treatment may support therapeutic optimisation in IBD patients

AU - James, Jaslin P.

AU - Nielsen, Boye Schnack

AU - Langholz, Ebbe

AU - Malham, Mikkel

AU - Høgdall, Estrid

AU - Riis, Lene Buhl

N1 - Publisher Copyright: © 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

PY - 2023

Y1 - 2023

N2 - Background and aims: Tumour necrosis factor-α (TNF) antagonists have improved the management of inflammatory bowel disease (IBD), however, their usage and administration persist to be suboptimal. Here, we examined the relationship between tissue-specific TNF mRNA expression in mucosal biopsies from IBD patients and anti-TNF treatment response. Methods: Archived tissue samples from patients with luminal IBD that had all been or were in treatment with anti-TNF were included (18 adults and 24 paediatric patients). Patients were stratified into three groups according to anti-TNF response: responders, primary non-responders (PNR) and secondary loss of response (SLOR). TNF mRNA was detected using RNAscope in situ hybridisation (ISH) and the expression was quantified using image analysis. Results: The ISH analysis showed varying occurrence of TNF mRNA positive cells located in lamina propria and often with increased density in lymphoid follicles (LF). Consequently, expression estimates were obtained in whole tissue areas with and without LF. Significantly higher TNF mRNA expression levels were measured in adults compared to paediatric patients in both the analyses with and without LF (p =.015 and p =.016, respectively). Considering the relation to response, the adult and paediatric patients were evaluated separately. In adults, the TNF expression estimates were higher in PNRs compared to responders with and without LF (p =.017 and p =.024, respectively). Conclusion: Our data indicate that adult PNR have significantly higher TNF mRNA levels than responders. This suggests that higher anti-TNF dose may be considered for IBD patients with high TNF mRNA expression estimates from the start of treatment.

AB - Background and aims: Tumour necrosis factor-α (TNF) antagonists have improved the management of inflammatory bowel disease (IBD), however, their usage and administration persist to be suboptimal. Here, we examined the relationship between tissue-specific TNF mRNA expression in mucosal biopsies from IBD patients and anti-TNF treatment response. Methods: Archived tissue samples from patients with luminal IBD that had all been or were in treatment with anti-TNF were included (18 adults and 24 paediatric patients). Patients were stratified into three groups according to anti-TNF response: responders, primary non-responders (PNR) and secondary loss of response (SLOR). TNF mRNA was detected using RNAscope in situ hybridisation (ISH) and the expression was quantified using image analysis. Results: The ISH analysis showed varying occurrence of TNF mRNA positive cells located in lamina propria and often with increased density in lymphoid follicles (LF). Consequently, expression estimates were obtained in whole tissue areas with and without LF. Significantly higher TNF mRNA expression levels were measured in adults compared to paediatric patients in both the analyses with and without LF (p =.015 and p =.016, respectively). Considering the relation to response, the adult and paediatric patients were evaluated separately. In adults, the TNF expression estimates were higher in PNRs compared to responders with and without LF (p =.017 and p =.024, respectively). Conclusion: Our data indicate that adult PNR have significantly higher TNF mRNA levels than responders. This suggests that higher anti-TNF dose may be considered for IBD patients with high TNF mRNA expression estimates from the start of treatment.

KW - Image analysis

KW - inflammation

KW - lymphoid follicle

KW - mucosal TNF mRNA

KW - Paediatric IBD

KW - quantitative in situ hybridisation

KW - treatment non-response

KW - Tumour necrosis factor

U2 - 10.1080/00365521.2023.2217313

DO - 10.1080/00365521.2023.2217313

M3 - Journal article

C2 - 37246424

AN - SCOPUS:85161063064

VL - 58

SP - 1237

EP - 1245

JO - Scandinavian Journal of Gastroenterology

JF - Scandinavian Journal of Gastroenterology

SN - 0036-5521

IS - 11

ER -