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.
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.
Background/Aims
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.
Methods
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.
Results
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.
Conclusions
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.
Aim
The frequency and details of nonalcoholic fatty liver disease (NAFLD) complications in patients with inflammatory bowel disease (IBD) remain unclear. This study aimed to clarify characteristics of NAFLD in non-obese patients with IBD.
Methods
Patients with IBD who underwent abdominal computed tomography (CT) examination at our hospital between 2005 and 2020 were retrospectively identified and enrolled in the study. The primary endpoint was the complication rate of NAFLD in patients with IBD. Secondary endpoints were the clinical characteristics of patients with IBD and comorbid NAFLD and their association with nutritional and inflammatory parameters.
Results
Twenty-one (21.9%) of 96 eligible patients with IBD also had NAFLD. In non-obese patients (defined as patients with a body mass index < 25 kg/m2), CRP (P < 0.0001) and alanine aminotransferase (P = 0.0183) levels were higher and the albumin level (P = 0.0046) and prognostic nutritional index (PNI; P = 0.0022) values were lower in patients with NAFLD than in those without NAFLD. The PNI value was positively correlated (P = 0.0001) and the CRP level was negatively correlated (P = 0.0008) with the hepatosplenic ratio. However, the PNI (P < 0.05) and CRP level (P < 0.001) improved numerically over time after computed tomography in the group with NAFLD than in the group without NAFLD.
Conclusions
Worsening nutritional status may be an indicator of NAFLD in patients with IBD. Diagnosis of NAFLD on CT imaging might be useful in patients with IBD not only for early detection of NAFLD but also for assessment of the need for therapeutic intervention for IBD.
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