Ustekinumab is an effective therapy for adult Crohn's disease (CD), but data in paediatric CD patients are scarce. The aim of the study was to describe the real-life effectiveness and safety of ustekinumab in paediatric CD. This is a multicentre review of children with Crohn's disease treated with ustekinumab. The aim of our study was to describe the effectiveness and safety of ustekinumab in paediatric real-life practice. This is a study of the Paediatric IBD (inflammatory bowel disease) Porto group of ESPGHAN. Corticosteroid (CS)- and exclusive enteral nutrition (EEN)-free remission, defined as weighted Paediatric Crohn's Disease Activity Index (wPCDAI) < 12.5, and physician global assessment (PGA) were determined at weeks 12 and 52. A total of 101 children were included at a median age of 15.4 years (IQR 12.7-17.2) with a median follow-up of 7.4 months (IQR 5.6-11.8). Ninety-nine percent had received prior anti-TNF, 63% ≥ 2 anti-TNFα therapies and 22% vedolizumab. Baseline median wPCDAI was 39 (IQR 25-57.5) (71 (70%) patients with moderate-severe activity). Weeks 12 and 52 CS- and EEN-free remission were both 40.5%. Clinical response at week 6, iv induction route and older age at onset of ustekinumab treatment were predictive factors associated with clinical remission at week 12. Seven minor adverse events probably related to ustekinumab were reported. One patient died from an unrelated cause. Conclusion: Our results suggest that ustekinumab is effective and safe in children with chronically active or refractory CD. What is Known: • Ustekinumab is an effective therapy for adult moderate to severe Crohn's disease (CD). • Off-label use of ustekinumab in children is increasing especially in anti-TNF refractory CD. What is New: • Is the largest cohort of real-world use of ustekinumab in paediatric CD to date. • Clinical response at week 6, iv induction and older age at onset of ustekinumab were predictive factors associated with clinical response at week 12.

• Klíčová slova
• Children, Crohn’s disease, Exclusive enteral nutrition, Ustekinumab, wPCDAI,
• MeSH
• Crohnova nemoc * farmakoterapie   MeSH
• dítě MeSH
• indukce remise MeSH
• lidé MeSH
• mladiství MeSH
• retrospektivní studie MeSH
• stupeň závažnosti nemoci MeSH
• ustekinumab * terapeutické užití   MeSH
• výsledek terapie MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• Názvy látek
• ustekinumab * MeSH

In this study, the effects of vitamin D3 (Vit. D) and a stinging nettle [Urtica dioica L. (UD)] extract were examined using histopathological and immunohistochemical methods in the stomach tissues of an experimentally created rat model of Crohn's disease (CD). The CD model was created using trinitrobenzene sulfonic acid (TNBS). The animals in the study were divided into control, TNBS, TNBS+Vit. D, and TNBS+UD groups. At the end of the experiment, the animals were euthanised and their stomach tissues were evaluated for necrosis, degeneration, apoptosis, and inflammation. Additionally, an immunohistochemical method was applied to determine the somatostatin (SSTR), aquaporin-1 (AQP-1), caspase-3, and tumour necrosis factor-alpha (TNF-α) immunoreactivity in the gastric tissues. In the evaluations, degenerative and necrotic changes and mononuclear cell infiltration areas were observed in the TNBS group, but such changes could be improved with Vit. D and UD applications. The results suggest that the combination of the Vit. D and UD extract may have a protective and therapeutic role in mitigating TNBS-induced damage to the gastric tissues, potentially through the regulation of SSTR, AQP-1, caspase-3, and TNF-α expression. This indicates a promising avenue for further research and the exploration of these compounds in the context of gastrointestinal health.

• Klíčová slova
• Crohn’s disease, TNF-α, aquaporin-1, somatostatin,
• Publikační typ
• časopisecké články MeSH

It is well known that some pathological conditions, especially of autoimmune etiology, are associated with the HLA (human leukocyte antigen) phenotype. Among these diseases, we include celiac disease, inflammatory bowel disease, autoimmune enteropathy, autoimmune hepatitis, primary sclerosing cholangitis and primary biliary cholangitis. Immunoglobulin G4-related diseases (IgG4-related diseases) constitute a second group of autoimmune gastrointestinal, hepatobiliary and pancreatic illnesses. IgG4-related diseases are systemic and rare autoimmune illnesses. They often are connected with chronic inflammation and fibrotic reaction that can occur in any organ of the body. The most typical feature of these diseases is a mononuclear infiltrate with IgG4-positive plasma cells and self-sustaining inflammatory response. In this review, we focus especially upon the hepatopancreatobiliary system, autoimmune pancreatitis and IgG4-related sclerosing cholangitis. The cooperation of the gastroenterologist, radiologist, surgeon and histopathologist is crucial for establishing correct diagnoses and appropriate treatment, especially in IgG4 hepatopancreatobiliary diseases.

• Klíčová slova
• IgG4-related hepatopathy, IgG4-related sclerosing cholangitis, autoimmune hepatitis, autoimmune pancreatitis, celiac disease, human leukocyte antigen, inflammatory bowel disease, primary biliary cholangitis, primary sclerosing cholangitis,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Lactococcus lactis, a probiotic bacterium of food origin, has recently been demonstrated as a suitable strain for the production and in vivo delivery of therapeutically important proteins into the gut. We aimed to engineer recombinant L. lactis cells producing/secreting REX binding proteins that have been described as IL-23 receptor (IL-23R) blockers and IL-23R antagonists suppressing the secretion of cytokine IL-17A, a pivotal step in the T-helper Th17-mediated pro-inflammatory cascade, as well as in the development of autoimmune diseases, including inflammatory bowel disease (IBD). To reach this goal, we introduced cDNA sequences coding for REX009, REX115, and REX125 proteins into plasmid vectors carrying a Usp45 secretion signal, a FLAG tag sequence consensus, and a LysM-containing cA surface anchor (AcmA), thus allowing cell-surface peptidoglycan anchoring. These plasmids, or their non-FLAG/non-AcmA versions, were introduced into L. lactis host cells, thus generating unique recombinant L. lactis-REX strains. We demonstrate that all three REX proteins are expressed in L. lactis cells and are efficiently displayed on the bacterial surface, as tested by flow cytometry using an anti-FLAG antibody conjugate. Upon 10-fold concentration of the conditioned media, a REX125 secretory variant can be detected by Western blotting. To confirm that the FLAG/non-FLAG REX proteins displayed by L. lactis retain their binding specificity, cell-surface interactions of REX proteins with an IL-23R-IgG chimera were demonstrated by flow cytometry. In addition, statistically significant binding of secreted REX009 and REX115 proteins to bacterially produced, soluble human IL-23R was confirmed by ELISA. We conclude that REX-secreting L. lactis strains were engineered that might serve as IL-23/IL-23R blockers in an experimentally induced mouse model of colitis.

• Klíčová slova
• IL-23 cytokine, IL-23R, albumin-binding domain, binding protein, lactococcus, surface display,
• Publikační typ
• časopisecké články MeSH