P543 UC remission mucosa displays upregulated inflammatory mediators

C. Arkteg1, R. Goll2, M. Dixon Gundersen1, E. Anderssen1, C.G. Fenton1, J. Florholmen2

1Research Group Gastroenterology Nutrition, Institute of Clinical Medicine, UiT the Arctic University of Norway, Tromsø, Norway, 2Division of Internal Medicine, Department of Gastroenterology, Tromsø, Norway

Background

Ulcerative colitis (UC) is a chronic inflammatory bowel disease. In UC, a wide range of criteria is used for disease remission, with few studies investigating the differences between disease remission and normal control groups. This paper compares known inflammatory and healing mediators in the mucosa of UC in clinical remission and normal controls, in order to better describe the remission state and the fundamental pathology

Methods

Mucosal biopsies from 72 study participants (44 UC and 24 normal controls) were included from the Advanced Study of inflammatory bowel disease (ASIB Study), Arctic University of Norway, Norway. Clinical remission was defined as Mayo clinical score ≤ 2, with endoscopic subscores of ≤ 1. Targeted gene transcription analyses were performed by quantitative polymerase chain reaction (qPCR) and using hydrolysis probes and SYBR-green.

Results

Among the mucosal transcripts examined, 10 genes were regulated in remission vs. normal controls, 8 upregulated pro-inflammatory transcripts (IL1B, IL33, TNF, TRAF1, CLDN2, STAT1, STAT3 and IL13Ra2) and 2 downregulated (pro-inflammatory TBX21 and anti-inflammatory TGFB1). Between the active and normal group, 5 additional genes were differently regulated CASP8, ADAM17, DFB1 and TFF3 were up-regulated while CHUK was down-regulated. Several master transcription factors for T-cell development (TBX21, GATA3, FOXP3, RORC and SPI1) and important inflammatory mediators (IL33, IL6, TGFB, IL10 and TLR4) were upregulated in patients with Mayo endoscopic score of 1 in comparison to 0.

Conclusion

The mucosa of UC in clinical and endoscopic remission differs from normal mucosa, suggesting a remaining dysregulation of inflammatory and wound healing mechanisms. In addition, there is a significant expression difference between mayo endoscopic score of 1 and 0. This difference indicates that t-cell differentiation is still ongoing in the Mayo endoscopic subscore (MES) of 1. Interestingly, TNF did not differ between MES 0 and 1 suggesting an alternative inflammatory pathway in low-grade UC inflammation.