Increased mucosal IL-12 expression is associated with relapse of ulcerative colitis

Abstract

Background The role of IL-12/23 in the pathogenesis of ulcerative colitis (UC) is unclear. We analyzed mucosal IL-12/23 expression and its relationship with endoscopic severity, histological activity, and UC relapse. Methods Rectal biopsies were collected from 70 UC patients with clinical remission. IL-12, IL-23, IFN-γ, IL-17A, and IL-17F mRNA expression was measured by real-time PCR. Endoscopic severity and histological activity were evaluated using the Mayo endoscopic subscore (MES) and the Geboes score, respectively. Results The longest follow-up period was 51 months. Thirty-four patients relapsed during the study period. Samples from these subsequently relapsed patients formed the “relapse” group, while those from patients that did not relapse formed the “remission” group. IL-12 (P = 0.0003) and IL-23 (P = 0.014) mRNA expression was significantly higher in the relapse than the remission group. Expression of IL-23 (P = 0.015) but not IL-12 (P = 0.374) was correlated with MES. However, in patients with an MES of 0 and 1, IL-12 expression was statistically higher in the relapse than the remission group (P = 0.0015, P = 0.0342). IL-12 and IL-23 expression did not vary significantly between histologically active and inactive mucosa; both were higher in histologically inactive patients in the remission group (IL-12: P = 0.0002, IL-23: P = 0.046). Conclusions Rectal IL-12 and IL-23 expression was elevated in the relapse group, but IL-12 was more strongly associated with UC relapse, irrespective of endoscopic severity and histological activity. Mucosal IL-12 was elevated in patients with deep mucosal healing. Our results suggest an important role of IL-12 in UC pathogenesis and the molecular mechanism of UC relapse.

Cytokine and chemokine profiles in ulcerative colitis relapse after coronavirus disease 2019 vaccination

“…Expression of some pro-inflammatory cytokines and chemokines correlates to endoscopic disease activity. ( 28 , 29 ) We analyzed mRNA expression of cytokines and chemokines based on MES. We could not perform statistical analyses since three UC flare-up patients were judged as MES 2 ( n = 2) and MES 3 ( n = 1).…”

“…( 33 , 34 ) UC relapse was defined as aggravation of UC-associated symptoms and UC aggravation based on endoscopic findings. ( 28 , 29 ) Endoscopic and histological disease activities were assessed by MES and Nancy histological index, respectively. The clinical characteristics of the patients with active UC not associated with COVID-19 vaccination are summarized in Table 2 .…”

Myeloid cell influx into the colonic epithelium is associated with disease severity and non-response to anti-Tumor Necrosis Factor Therapy in patients with Ulcerative Colitis

“…Accordingly and associated with the loss of epithelial tethers, physiological EC residents, especially  + IELs which are known to enhance barrier function 56 , dampen inflammation 57 and regulate  + IELs 58 were significantly depleted from the EC in UC as was previously reported in CD 26 .  + IEL loss from the EC was accompanied by a major influx of CD4 +  + IELs, especially TH17 and TREG cells encoding a number of pathogenic, pro inflammatory programs, associated with tissue damage and worsening of disease activity 57,59 that included TNFR2 signaling 60 , TCR activation 61,62 , IL-2/STAT5 signaling 63 , IL-7 signaling 64 , IL-9 signaling 65 and IL-12 signaling 66 .…”

Disease clearance in ulcerative colitis: Setting the therapeutic goals for future in the treatment of ulcerative colitis

“…Recent studies have defined a molecular signature associated with the remission of ulcerative colitis. Higher expression of ALOX15 (related to eosinophil and mast cells metabolism) was linked to a higher likelihood of remission ( 56 ), but an increased risk for a future relapse was associated with higher expression of IL21, IL17F, and IL17A in MES 0/1 patients ( 60 ) as well as IL12 and IL23 ( 61 ). The molecular profile associated with endoscopic remission (MES ≤ 1) has been linked to increased expression of IFITM1, ITGB2, IL1R2, and IL2RA ( 62 ).…”