Epstein-Barr virus infection in ulcerative colitis: a clinicopathologic study from a Chinese area.

BACKGROUND: Opportunistic Epstein-Barr virus (EBV) infection in patients with ulcerative colitis (UC) has attracted increasing attention. This study aimed to evaluate the clinicopathological characteristics and clinical outcomes of UC with intestinal EBV infection and to explore the predictive value of blood EBV DNA for the presence of EBV in the intestine. METHODS: Both peripheral blood and intestinal biopsies from 92 consecutive UC inpatients were included in this study. Normal colonic mucosal tissues from 20 colon cancer patients were used as controls. EBV testing and assessment were performed by EBV-DNA polymerase chain reaction (PCR), EBV-encoded small RNA in situ hybridization (EBER-ISH) and immunohistochemistry. RESULTS: A total of 36 patients (39.1%) had UC with superimposed EBV colitis [EBER greater than 2/high-power field (HPF)]. EBER counts and disease activity were significantly correlated (p < 0.05). The major endoscopic findings revealed more irregular and longitudinal ulcers in patients with superimposed EBV colitis (p = 0.016, p = 0.021, respectively). Age, steroid dependence, and irregular ulcerations were identified as possible risk factors. The best EBER cut-off point for outcome prediction was 2.5/HPF. At a cut-off value of 2035 copies/ml, the sensitivity and specificity of the blood EBV-DNA PCR analysis for predicting EBV presence in the intestine were 76.5% and 68.5%, respectively. EBV-infected cells in UC with high EBV concentrations mainly included B lymphocytes by clinicopathology, and the infection might have progressed from the latent to the lytic phase of the EBV life cycle. CONCLUSION: The EBER count is positively correlated with disease activity. The best cut-off point for outcome prediction is 2.5/HPF. A high EBV viremia load may effectively predict EBV presence in the colonic mucosa.

Systematic review with meta-analysis of partial enteral nutrition for the maintenance of remission in Crohn's disease.

Although enteral nutrition (EN) is effective for induction therapy in Crohn's disease (CD), it remains unclear whether partial enteral nutrition (PEN), i.e., EN, along with a daily diet, is effective for maintenance therapy in CD. It was hypothesized that PEN would be effective as a maintenance therapy in CD. This meta-analysis aimed to evaluate the efficacy and safety of PEN for maintenance therapy in CD. PubMed, EMBASE, Web of Science, and Cochrane Library were searched up to January 2019 for eligible prospective controlled trials, and then a meta-analysis was conducted. The primary outcome was clinical relapse, as defined in the primary studies. Eight studies with 429 patients were included in the meta-analysis. The rate of clinical relapse at 0.5 to 2 years was significantly lower in patients receiving PEN (420-1800 kcal/d) than in those not receiving nutrition therapy (RR: 0.67, 95% CI: 0.54-0.82, P < .01; number needed to treat = 5, P < .01). Patients receiving PEN exhibited a higher frequency of clinical remission maintenance at 0.5 to 1 year (67%) than did those not receiving nutrition therapy (48%; RR: 1.32, 95% CI: 1.07-1.64, P = .01). The total adverse event rate was comparable in the two groups (RR: 3.60, 95% CI: 0.70-18.66, P = .13). PEN may be more effective than the absence of EN therapy for the maintenance of remission in CD with a good safety profile.

Human induced pluripotent stem cell-derived mesenchymal stem cells promote healing via TNF-α-stimulated gene-6 in inflammatory bowel disease models.

Therapeutic applications of tissue-derived mesenchymal stem cells (MSCs) are hindered by their limited expansion ability and variation across donors. Human induced pluripotent stem cell (iPSC)-derived MSCs show greater expandability and therefore offer potential for use in tissue repair therapies. Here we explored the regenerative effects of iPSC-MSCs and the mechanisms by which iPSC-MSCs promote mucosal healing via tumor necrosis factor-α-stimulated gene 6 (TSG-6) in mouse models of inflammatory bowel disease (IBD). Human iPSCs were induced to differentiate into MSCs following a clinically compliant protocol. The iPSC-MSC treatment promoted mucosal healing in colitic mice, accompanied by increased epithelial cell proliferation, CD44-positive cells, and Lgr5-positive cells. TSG-6 knockdown in iPSC-MSCs or blocking of hyaluronan-CD44 interactions by PEP-1 abrogated the therapeutic effects of iPSC-MSCs, whereas use of recombinant TSG-6 showed therapeutic effects similar to those of iPSC-MSCs. A mouse or patient-derived organoid culture system was developed. Organoids co-cultured with iPSC-MSCs showed increased epithelial cell proliferation, CD44-positive cells, and Lgr5-positive cells, which was abolished by TSG-6 knockdown. TSG-6-induced promoting effects in organoids were dependent on Akt activation and abrogated by the anti-CD44 antibody or MK2206. In conclusion, iPSC-MSCs promoted epithelial cell proliferation to accelerate mucosal healing in a murine colitis model via TSG-6 through hyaluronan-CD44 interactions in an Akt-dependent manner, demonstrating a patient-specific "off-the-shelf" format for IBD treatment.