Crohn’s disease and ulcerative colitis are two important categories of human inflammatory bowel disease(IBD). Because the precise mechanisms of the inflammation and immune responses in IBD have not ...been fully elucidated,the treatment of IBD primarily aims to inhibit the pathogenic factors of the inflammatory cascade. Inconsistencies exist regarding the response and side effects of the drugs that are currently used to treat IBD. Recent studies have suggested that the use of nanomedicine might be advantageous for the treatment of intestinal inflammation because nanosized molecules can effectively penetrate epithelial and inflammatory cells. We reviewed nanomedicine treatments,such as the use of small interfering RNAs,antisense oligonucleotides,and anti-inflammatory molecules with delivery systems in experimental colitis models and clinical trials for IBD based on a systematic search. The efficacy and usefulness of the treatments reviewed in this manuscript have been demonstrated in experimental colitis models and clinical trials using various types of nanomedicine. Nanomedicine is expected to become a new therapeutic approach to the treatment of IBD.
Anti-tumor necrosis factor alpha (TNF-α) antibodies are effective in patients with inflammatory bowel disease (IBD). However, the effect is not optimal because a sufficient concentration of ...antibodies cannot be maintained at the site of inflammation. Thus, a macromolecular complex was developed with schizophyllan (SPG) and antisense oligonucleotides. In the present study, an SPG-antisense TNF-α complex was prepared, and its therapeutic efficacy was examined using a dextran sodium sulfate (DSS)-induced colitis model. The TNF-α production in CD11b+ macrophages significantly increased in the colon of DSS-treated mice. Dectin-1, a receptor of SPG, binds with SPG and is subsequently taken into the cells via phagocytosis. The expression of dectin-1 by CD11b+ macrophages significantly increased in DSS-treated mice. Flow cytometry revealed that the uptake of SPG-antisense TNF-α in the macrophages was efficient. TNF-α production was suppressed significantly by SPG-antisense TNF-α in vitro, which was administered via enema to evaluate its efficacy. The intrarectal administration of SPG-antisense TNF-α ameliorated the intestinal inflammation. In this study, we showed that the delivery system that conjugates SPG and antisense can have higher therapeutic efficacy. Thus, the new therapeutic approach presented in this study may be used in the management of IBD.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The aim of the present study was to quantify calprotectin levels using an enzyme-linked immunosorbent assay (ELISA) and a point-of-care test (POCT) in patients with inflammatory bowel disease. ...Overall, 113 patients with ulcerative colitis (UC; 51 men and 62 women) and 42 patients with Crohn's disease (CD; 29 men and 13 women), who were scheduled to undergo a colonoscopy, were prospectively enrolled and scored endoscopically and clinically. An additional 96 healthy, age-matched subjects served as the normal controls. Feces and blood samples from the patients with UC and CD, and the normal controls were analyzed. These patients had received adequate medical treatment. The tissue distribution of calprotectin was investigated using immunohistochemistry. The fecal calprotectin levels, as measured using an ELISA, were correlated with the endoscopic and clinical disease activities and laboratory parameters, including serum levels of hemoglobin (Hb), albumin and C-reactive protein, and erythrocyte sedimentation rate, particularly among the patients with UC. The fecal Hb level was close to that of the fecal calprotectin level (r=0.57; P<0.0001). The fecal calprotectin level measured using an ELISA was well-correlated with the fecal calprotectin level measured using the POCT (r=0.81; P<0.0001), but was not correlated with the serum calprotectin level (r=0.1013; P=0.47). An immunohistochemical investigation revealed that patients with both UC and CD had higher neutrophil and monocyte/macrophage calprotectin-positive cell expression levels, compared with those in the normal controls. Fecal calprotectin was considered a reliable marker for disease activity, and the assessment of fecal calprotectin via POCT showed potential as a rapid and simple measurement in clinical settings.
Proteinase 3 antineutrophil cytoplasmic antibody (PR3-ANCA) is a serologic marker for granulomatosis with polyangiitis. However, recent studies have also shown their role as diagnostic markers for ...ulcerative colitis (UC). This study was performed to investigate the clinical roles of PR3-ANCAs in the disease severity, disease extension, and clinical course of UC.
Serum PR3-ANCAs were measured in 173 UC patients including 77 patients with new-onset patients UC diagnosed within 1 month, 110 patients with Crohn's disease, 48 patients with other intestinal diseases, and 71 healthy controls. Associations between the PR3-ANCA titer and clinical data, such as disease severity, disease extension, and clinical course, were assessed. The clinical utility of PR3-ANCA measurement was evaluated by receiver operating characteristic (ROC) analysis.
PR3-ANCA ≥3.5 U/mL demonstrated 44.5% sensitivity and 95.6% specificity for the diagnosis of UC in all patients. PR3-ANCA positivity was more prevalent in the 77 new-onset UC patients (58.4%). In this group, the disease severity and extension were more severe in PR3-ANCA positive patients than in PR3-ANCA negative group (p<0.001). After treatment, the partial Mayo scores were significantly decreased with the PR3-ANCA titers. The proportion of patients who required steroids for induction therapy was significantly higher among PR3-ANCA positive than negative group. ROC analysis revealed that PR3-ANCA ≥3.5 U/mL had 75% sensitivity and 69.0% specificity for steroid requirement in new-onset UC patients.
Our results indicate that PR3-ANCA measurement is useful not only for diagnosing UC but also for evaluating disease severity and extension and predicting the clinical course.
Background
Small bowel stricture is one of the most common complications in patients with Crohn’s disease (CD). Endoscopic balloon dilatation (EBD) is a minimally invasive treatment intended to avoid ...surgery; however, whether EBD prevents subsequent surgery remains unclear. We aimed to reveal the factors contributing to surgery in patients with small bowel stricture and the factors associated with subsequent surgery after initial EBD.
Methods
Data were retrospectively collected from surgically untreated CD patients who developed symptomatic small bowel stricture after 2008 when the use of balloon-assisted enteroscopy and maintenance therapy with anti-tumor necrosis factor (TNF) became available.
Results
A total of 305 cases from 32 tertiary referral centers were enrolled. Cumulative surgery-free survival was 74.0% at 1 year, 54.4% at 5 years, and 44.3% at 10 years. The factors associated with avoiding surgery were non-stricturing, non-penetrating disease at onset, mild severity of symptoms, successful EBD, stricture length < 2 cm, and immunomodulator or anti-TNF added after onset of obstructive symptoms. In 95 cases with successful initial EBD, longer EBD interval was associated with lower risk of surgery. Receiver operating characteristic analysis revealed that an EBD interval of ≤ 446 days predicted subsequent surgery, and the proportion of smokers was significantly high in patients who required frequent dilatation.
Conclusions
In CD patients with symptomatic small bowel stricture, addition of immunomodulator or anti-TNF and smoking cessation may improve the outcome of symptomatic small bowel stricture, by avoiding frequent EBD and subsequent surgery after initial EBD.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Studies on serum leucine-rich alpha-2 glycoprotein (LRG) in inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), are scarce; the methods for estimating ...disease activity are less established, particularly for CD. This study is aimed at evaluating the utility of serum LRG as a potential inflammatory marker for IBD and to investigate the LRG gene expression in peripheral blood mononuclear cells (PBMCs) as a possible source of serum LRG. Overall, 98 patients with UC and 96 patients with CD were prospectively enrolled and clinically evaluated; 92 age-matched individuals served as the healthy controls. The blood samples were analyzed for serum LRG levels and routine laboratory parameters. Disease activity was assessed clinically and endoscopically. Finally, LRG gene expression in the PBMCs from a different cohort (41 patients with UC, 34 patients with CD, and 30 healthy controls) was examined. The serum LRG levels were higher during active disease than during inactive disease; additionally, serum LRG levels were positively correlated with clinical disease activity, C-reactive protein (CRP) levels, and other laboratory parameters in patients with UC and CD and with endoscopic disease activity in UC. UC and CD showed comparable areas under the curve (AUC) values for determining clinical remission and differentiating between endoscopic remission associated with LRG and CRP. The levels of LRG mRNA were also increased in PBMCs from patients with UC and CD and reflected disease activity. These data suggest that serum LRG, originated partially from PBMCs, is an inflammatory marker in UC and CD. A large-scale well-designed study should be conducted in the future to more accurately reveal the clinical significance of LRG in patients with IBD.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Background and Aim
Proteinase 3 antineutrophil cytoplasmic antibodies (PR3‐ANCAs) are well‐known serological markers for granulomatosis with polyangiitis, but their role as serological markers for ...inflammatory bowel disease remains uncertain. The present study aimed to evaluate the diagnostic and clinical role of PR3‐ANCAs as markers for inflammatory bowel disease.
Methods
Using a new methodology with chemiluminescence enzyme immunoassay, serum PR3‐ANCA titers were assessed in 102 patients with ulcerative colitis (UC), 67 patients with Crohn's disease (CD), 44 controls with other intestinal diseases, and 66 healthy controls. Associations with clinical data were investigated. The diagnostic role of PR3‐ANCAs was evaluated by receiver operating characteristic analysis.
Results
Proteinase 3 antineutrophil cytoplasmic antibody titers were significantly higher in patients with UC than in those with CD patients, patients with intestinal diseases (intestinal controls), and healthy controls (all P < 0.001). Receiver operating characteristic analysis demonstrated an area under the curve of 0.85 (95% confidence interval: 0.83–0.87) and showed that the manufacturer's cutoff value (3.5 U/mL) had a sensitivity of 39.2% and specificity of 96.6% for UC. There was a significant difference between PR3‐ANCA‐positive and PR3‐ANCA‐negative patients with regard to disease duration (P < 0.05) and disease severity (P < 0.01).
Conclusions
Proteinase 3 antineutrophil cytoplasmic antibodies were significantly more prevalent in patients with UC than in those with CD and controls. Our results suggested the role of PR3‐ANCAs as serological markers for aiding in diagnosing UC and evaluating disease severity. Further prospective studies are needed across multiple populations of patients and ethnic groups.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
B cells possess a variety of immune functions that are involved in normal and abnormal immune responses, including autoimmune disorders. Through murine models of intestinal inflammation, we here ...demonstrate a B cell subset that is induced in gut-associated lymphoid tissues and is characterized by CD1d upregulation. This B cell subset appears under a chronic inflammatory environment, produces IL-10, and suppresses progression of intestinal inflammation by downregulating inflammatory cascades associated with IL-1 upregulation and STAT3 activation rather than by altering polarized T helper responses. This study indicates that B cells, by producing cytokines such as IL-10, can act as regulatory cells in immunologically mediated inflammatory reactions.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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