Prevalence and Significance of Autoantibody Seropositivity in Children with Wilson’s Disease

Autoantibodies occur in healthy subjects as well as in children with Wilson’s disease (WD), but their prevalence and significance are unknown. Thus, we aimed to assess the prevalence of autoantibodies and autoimmune markers, and their relationship to liver injury in WD children. The study included 74 WD and 75 healthy children as a control group. Patients with WD underwent transient elastography (TE) examinations, as well as determination of liver function tests, copper metabolism markers, and serum immunoglobulins (Ig). In the sera of the WD patients and controls, anti-nuclear (ANA), anti-smooth muscle, anti-mitochondrial, anti-parietal cell, anti-liver/kidney microsomal, anti-neutrophil cytoplasmic autoantibodies, and specific celiac antibodies were determined. Among the autoantibodies, only the prevalence of ANA in children with WD was higher than in the controls. There was no significant relationship between the presence of autoantibodies and liver steatosis or stiffness after TE. However, advanced liver stiffness (E > 8.2 kPa) was related to IgA, IgG, and gamma globulin production. The type of treatment did not influence the prevalence of autoantibodies. Our results suggest that autoimmune disturbances in WD might not be directly related to liver damage as expressed by steatosis and/or liver stiffness after TE

The Impact of a CMV Infection on the Expression of Selected Immunological Parameters in Liver Tissue in Children with Biliary Atresia

The pathogenesis of biliary atresia (BA) is still not clear. The aim of this study was to evaluate the expression of selected immunological parameters in liver tissue in BA children based on CMV/EBV infection status. Eight of thirty-one children with newly diagnosed BA were included in this prospective study and assigned to two groups (I with active infection, II without active or past infection). All studies were performed on surgical liver biopsies. To visualize CD8+ T cells and CD56 expression, immunohistochemical staining was performed. The viral genetic material in the studied groups was not found, but CMV infection significantly affected the number of CD8+ lymphocytes in both the portal area and the bile ducts. The average number of CD8+ cells per mm2 of portal area in Groups I and II was 335 and 200 (p = 0.002). The average number of these cellsthat infiltrated the epithelium of the bile duct per mm2 in Group I and II was 0.73 and 0.37 (p = 0.0003), respectively. Expression of CD56 in the bile ducts corresponded to the intensity of the inflammatory infiltrate of CD8+ cells. Our results suggest that active CMV infection induces an increased infiltration of CD8+ lymphocytes, which could play a role in BA immunopathogenesis. Increased CD56 expression can be a sign of a newly formed bile structure often without lumen, suggesting inhibition of the maturation process in BA

Effects of Microencapsulated Sodium Butyrate, Probiotics and Short Chain Fructooligosaccharides in Patients with Irritable Bowel Syndrome: A Study Protocol of a Randomized Double-Blind Placebo-Controlled Trial

Irritable bowel syndrome (IBS) is a functional gastrointestinal disease in the pathogenesis of which gut dysbiosis may play an important role. Thus, probiotics, prebiotics, or microbiota metabolites, such as butyric acid, are considered to be effective therapy for IBS. However, there are still no trials presenting the efficacy of these three biotic components administered simultaneously. This study aims to evaluate the effects of the product comprising sodium butyrate, probiotics, and short-chain fructooligosaccharides (scFOS) on the severity of clinical IBS symptoms and the quality of life (IBS-QOL). This is a randomized double-blind placebo-controlled trial conducted in 120 adults with IBS diagnosed according to Rome IV criteria. The intervention group (n = 60) will receive a mixture of the following components: 300 mg of colon-targeted microencapsulated sodium butyrate combined with probiotic Lactobacillus strains (L. rhamnosus and L. acidophilus) and Bifidobacterium strains (B. longum, B. bifidum, B. lactis), and 64 mg of prebiotic scFOS. The control group (n = 60) will receive a placebo (maltodextrin). The primary outcomes will be changes in IBS symptoms with the use of the IBS-Severity Scoring System (IBS-SSS), IBS-Global Improvement Scale (IBS-GIS), IBS-Adequate Relief (IBS-AR), and IBS-QOL after 12 weeks of intervention. The secondary outcomes will be the type of stools, patient-recorded symptoms, adverse events, anthropometric and nutritional parameters, and inflammatory cytokine levels. The findings will provide the first evidence of the use of a combination of three biotic compounds in IBS. The study was registered in the clinicaltrials.gov registry under the number NCT05013060

The Effectiveness of Synbiotic Preparation Containing Lactobacillus and Bifidobacterium Probiotic Strains and Short Chain Fructooligosaccharides in Patients with Diarrhea Predominant Irritable Bowel Syndrome—A Randomized Double-Blind, Placebo-Controlled Study

The purpose of the randomized double-blind placebo-controlled trial was to assess the effectiveness of synbiotic preparation containing probiotic Lactobacillus rhamnosus FloraActive™ 19070-2, Lactobacillus acidophilus DSMZ 32418, Bifidobacterium lactis DSMZ 32269, Bifidobacterium longum DSMZ 32946, Bifidobacterium bifidum DSMZ 32403 and fructooligosaccharides in adult patients with diarrhea-dominant IBS (IBS-D). The study included eighty patients with moderate and severe IBS-D who were randomized to receive synbiotics or placebo for eight weeks. Finally, a total of sixty-eight patients finished the study. The primary endpoints included the assessment of the symptoms’ severity with IBS symptom severity scale (IBS-SSS), an improvement of IBS global symptoms with Global Improvement Scale (IBS-GIS) and adequate relief of symptoms after four and eight weeks of therapy. Secondary endpoints, which were collected by telephone interviewers three times a week included the assessment of individual IBS symptoms and adverse events. Synbiotic treatment in comparison to placebo significantly improved IBS-GIS (p = 0.043), and IBS-SSS score inducing a decrease in the total IBS-SSS (p = 0.042) and in domain-specific scores related to flatulence (p = 0.028) and bowel habit (p = 0.028) after four and eight weeks. Patients treated with synbiotics reported in weekly observations a significant amelioration in a feeling of incomplete bowel movements, flatulence, pain, stool pressure and diarrheal stools compared to those receiving placebo. There were no differences in adverse events between both groups. Concluding, the multi-strain synbiotic preparation was associated with a significant improvement in symptoms in IBS-D patients and was well-tolerated. These results suggest that the use of synbiotics offers a benefit for IBS-D patients. [Clinicaltrials.gov NCT04206410 registered 20 December 2019]

Narrow time window of metabolic changes associated with transition to overt heart failure in Tgaq*44 mice

Background The timing and consequences of alternations in substrate utilization in heart failure (HF) and their relationship with structural changes remain unclear. This study aimed to analyze metabolic changes associated with transition to overt heart failure in transgenic mouse model of HF resulting from cardiac-specific overexpression of constitutively active Gαq∗. Methods Structural changes quantified by morphometry, relative cardiac mRNA and protein expression of PPARα, FAT/CD36, CPT-1, GLUT-4 and glycolytic efficiency following administration of 1-13C glucose were investigated in 4-14-month-old Tgαq∗44 mice (TG), compared with age-matched FVB wild type mice (WT). Results Initial hypertrophy in TG (4-10-month of age) was featured by an accelerated glycolytic pathway that was not accompanied by structural changes in cardiomyocytes. In 10-month-old TG, cardiomyocyte elongation and hypertrophic remodeling and increased glycolytic flux was accompanied by relatively low expression of FAT/CD36, CPT-1 and PPARα. During the transition phase (12-month-old TG), a pronounced increase in PPARα with an increase in relative fatty acid (FA) flux was associated with anomalies of cardiomyocytes with accumulation of lipid droplets and glycogen as well as cell death. At the stage of overt heart failure (14-month-old TG), an accelerated glycolytic pathway with a decline in FA oxidation was accompanied by further structural changes. Conclusion Tgαq∗44 mice display three distinct phases of metabolic/structural changes during hypertrophy and progression to HF, with relatively short period of increase in FA metabolism, highlighting a narrow metabolic changes associated with transition to overt heart failure in Tgaq∗44 mice that have therapeutic significance

Transcriptional and Ultrastructural Analyses Suggest Novel Insights into Epithelial Barrier Impairment in Celiac Disease

Disruption of epithelial junctional complex (EJC), especially tight junctions (TJ), resulting in increased intestinal permeability, is supposed to activate the enhanced immune response to gluten and to induce the development of celiac disease (CD). This study is aimed to present the role of EJC in CD pathogenesis. To analyze differentially expressed genes the next-generation mRNA sequencing data from CD326+ epithelial cells isolated from non-celiac and celiac patients were involved. Ultrastructural studies with morphometry of EJC were done in potential CD, newly recognized active CD, and non-celiac controls. The transcriptional analysis suggested disturbances of epithelium and the most significant gene ontology enriched terms in epithelial cells from CD patients related to the plasma membrane, extracellular exome, extracellular region, and extracellular space. Ultrastructural analyses showed significantly tighter TJ, anomalies in desmosomes, dilatations of intercellular space, and shorter microvilli in potential and active CD compared to controls. Enterocytes of fetal-like type and significantly wider adherence junctions were observed only in active CD. In conclusion, the results do not support the hypothesis that an increased passage of gluten peptides by unsealing TJ precedes CD development. However, increased intestinal permeability due to abnormality of epithelium might play a role in CD onset

Combination of HLA-DQ2/-DQ8 Haplotypes and a Single MSH5 Gene Variant in a Polish Population of Patients with Type 1 Diabetes as a First Line Screening for Celiac Disease?

Patients with type 1 diabetes (T1D) are at increased risk for developing celiac disease (CD). The aim of the study was to assess the usefulness of celiac-specific human leukocyte antigen (HLA) haplotype and the rs3130484 variant of MSH5 gene, a previously described non-HLA variant associated with CD in the Polish population as a first-line screening for CD in T1D pediatric patients. Serological CD screening performed in the T1D group (n = 248) and healthy controls (n = 551) allowed for CD recognition in 20 patients (8.1%) with T1D (T1D + CD group). HLA-DQ2, HLA-DQ8 and the rs3130484 variant were genotyped with TaqMan SNP Genotyping Assays. The T1D + CD group presented a higher, but not statistically significant, frequency of HLA-DQ2 in comparison with T1D subjects. Combining the rs3130484 with HLA-DQ2/HLA-DQ8 typing significantly increased the sensitivity of HLA testing from 32.7% to 68.7%, and the accuracy of estimating CD prediction from 51.7% to 86.4% but decreased the specificity from 100% to 78.2%. The receiver operating characteristic curve analysis confirmed the best discrimination for the combination of both genetic tests with an area under curve reaching 0.735 (95% CI: 0.700–0.7690) in comparison with 0.664 (95% CI: 0.632–0.696) for HLA typing alone. Results show the low utility of HLA-DQ2/HLA-DQ8 typing for CD screening in T1D pediatric patients. Combination of the rs3130484 variant of the MSH5 gene and HLA testing increases both the sensitivity and the predictive value of the test accuracy, but still, the obtained values are not satisfactory for recommending such testing as the first-line screening for CD in T1D patients