BACKGROUND Several studies have employed animal models to explore the association between microbiota and interleukin(IL) 10 signaling;however,limited information is available about the human microbiome.AIM To characte...BACKGROUND Several studies have employed animal models to explore the association between microbiota and interleukin(IL) 10 signaling;however,limited information is available about the human microbiome.AIM To characterize the microbiome in patients with IL10 RA mutations and to explore the association between gut dysbiosis and disease severity.METHODS Fecal samples were collected from patients who were diagnosed with loss-offunction mutations in the IL10 RA gene between January 2017 and July 2018 at the Children’s Hospital of Fudan University.Age-matched volunteer children were recruited as healthy controls.Patients with Crohn’s disease(CD) were used as disease controls to standardize the antibiotic exposure.Microbial DNA was extracted from the fecal samples.All analyses were based on the 16 S rRNA gene sequencing data.RESULTS Seventeen patients with IL10 RA mutations(IL10 RA group),17 patients with pediatric CD, and 26 healthy children were included.Both patients with IL10 RA mutations and those with CD exhibited a reduced diversity of gut microbiome with increased variability.The relative abundance of Firmicutes was substantially increased in the IL10 RA group(P=0.02).On further comparison of the relative abundance of taxa between patients with IL10 RA mutations and healthy children,13 taxa showed significant differences.The IL10 RA-specific dysbiosis indices exhibited a significant positive correlation with weighted pediatric CD activity index and simple endoscopic score for CD.CONCLUSION In patients with IL10 RA mutations and early onset inflammatory bowel disease,gut dysbiosis shows a moderate association with disease severity.展开更多
This work aimed to find quantitative phenotypic traits that can be used to discriminate the levels of resistance/susceptibility to B. bovis and B. bigemina in two groups of cattle presenting the highest (H) or lowest ...This work aimed to find quantitative phenotypic traits that can be used to discriminate the levels of resistance/susceptibility to B. bovis and B. bigemina in two groups of cattle presenting the highest (H) or lowest (L) infection levels and Rhipicephalus microplus ticks count. The animals were selected from a previous study of 50 Canchim (5/8 Charolais/zebu) heifers raised in an endemic area for these parasites. These animals were evaluated regarding their TNFα, IL10, IFN-γ, IL12 and iNOS mRNA levels. No differences were found between these groups regarding TNFα, IFN-γ, IL12β or iNOS transcripts. However, the IL10 transcripts were significantly higher in the H group compared to the L group. Moreover, significant correlation coefficients were observed between B. bovis loads and both IL10 and IFN-γ transcripts, while no correlations were found for B. bigemina loads and all tested immune-related transcripts, suggesting that differential IL10 mRNA profiles were closely associated to B. bovis loads. Our results have contributed to a better understanding of the immune responses against Babesia infection, as we demonstrated that the IL10 cytokine levels might also influence or be influenced by parasitemia levels in persistently infected animals.展开更多
Background Bronchiolitis is the most common infection leading to hospitalization in infancy. Interleukin-10 (IL-10) is an anti-inflammatory cytokine, and in our previous study, IL10 gene rs1800896 (-1082A/G) polymorph...Background Bronchiolitis is the most common infection leading to hospitalization in infancy. Interleukin-10 (IL-10) is an anti-inflammatory cytokine, and in our previous study, IL10 gene rs1800896 (-1082A/G) polymorphism was associated with viral etiology of infant bronchiolitis. The objective of this study was to evaluate the associations between IL10 single nucleotide polymorphisms (SNPs) at rs1800890 (-3575A/T), rs1800871 (-819C/T) or rs1800872 (-592C/A) either alone or combined with the SNP at rs1800896 (-1082G/A), and the etiology and severity of infant bronchiolitis. Methods Data on four IL10 SNPs were available from 135 full-term infants, hospitalized for bronchiolitis at age less than 6 months, and from 378 to 400 controls. Viral etiology was studied, and oxygen support, feeding support and the length of stay in hospital were recorded during bronchiolitis hospitalization. Results Infants with rhinovirus bronchiolitis had the IL10 rs1800890 variant AT or TT genotype less often (18.2%) than controls (63.3%, P=0.03), and likewise, had the IL10 rs1800896 variant AG or GG genotype less often (27.3%) than con-trols (65.5%, P=0.009). Twenty-eight infants with bronchiolitis had the variant–variant Grs1800896Trs1800890 haplotype, and none of them had rhinovirus infection. The IL10 rs1800871 or rs1800872 genotypes showed no associations with viruses. No association was found between any genotypes and bronchiolitis severity measures. Conclusion IL10 rs1800890 and rs1800896 polymorphisms differed between infants with rhinovirus bronchiolitis and con-trols, but not between infants with respiratory syncytial virus bronchiolitis and controls.展开更多
AIM To analyze clinical differences between monogenic and nonmonogenic very-early-onset inflammatory bowel disease(VEO-IBD) and to characterize monogenic IBD phenotypically and genotypically via genetic testing. METHO...AIM To analyze clinical differences between monogenic and nonmonogenic very-early-onset inflammatory bowel disease(VEO-IBD) and to characterize monogenic IBD phenotypically and genotypically via genetic testing. METHODS A retrospective analysis of children aged 0 to 6 years diagnosed with VEO-IBD in a tertiary hospital in southern China from 2005 to 2017 was performed. Clinical data for VEO-IBD patients were collected, and genetic characteristics were analyzed using whole exome sequencing or target gene panel sequencing. RESULTS A total of 54 VEO-IBD patients were included in this study. A diagnosis of Crohn's disease(CD) or CDlike intestinal manifestations accounted for 72.2% of the VEO-IBD cases. Nine patients(16.7%) were identified by genetic testing as having monogenic IBD. The median age of diagnosis in the monogenic group was younger than that of the nonmonogenic IBD group, at 18 mo(interquartile range(IQR): 4 to 78) and 43.5 mo(IQR: 3 to 173), respectively; the P-value was 0.021. The incidence of perianal disease in the monogenic group was higher than that in the nonmonogenic group(P = 0.001). However, there were no significant differences between weight-forage and height-for-age Z-scores between the two groups, and similar laboratory results were obtained for the two groups. Five patients were found to have IL10 receptor mutation, two patients had chronic granulomatous disease, one patient had common variable immunodeficiency disease, and one patient had X-linked inhibitor of apoptosis protein deficiency. CONCLUSION A high proportion of monogenic IBD was observed in the VEO-IBD group, especially with disease onset before the age of 6 mo. Monogenic IBD and nonmonogenic IBD exhibited similar clinical features. Furthermore, next-generation sequencing played an important role in the diagnosis of monogenic IBD, and IL10 receptor mutation was predominant in this cohort.展开更多
基金Supported by the Jiujiu Charitable Trust-PIBD China.
文摘BACKGROUND Several studies have employed animal models to explore the association between microbiota and interleukin(IL) 10 signaling;however,limited information is available about the human microbiome.AIM To characterize the microbiome in patients with IL10 RA mutations and to explore the association between gut dysbiosis and disease severity.METHODS Fecal samples were collected from patients who were diagnosed with loss-offunction mutations in the IL10 RA gene between January 2017 and July 2018 at the Children’s Hospital of Fudan University.Age-matched volunteer children were recruited as healthy controls.Patients with Crohn’s disease(CD) were used as disease controls to standardize the antibiotic exposure.Microbial DNA was extracted from the fecal samples.All analyses were based on the 16 S rRNA gene sequencing data.RESULTS Seventeen patients with IL10 RA mutations(IL10 RA group),17 patients with pediatric CD, and 26 healthy children were included.Both patients with IL10 RA mutations and those with CD exhibited a reduced diversity of gut microbiome with increased variability.The relative abundance of Firmicutes was substantially increased in the IL10 RA group(P=0.02).On further comparison of the relative abundance of taxa between patients with IL10 RA mutations and healthy children,13 taxa showed significant differences.The IL10 RA-specific dysbiosis indices exhibited a significant positive correlation with weighted pediatric CD activity index and simple endoscopic score for CD.CONCLUSION In patients with IL10 RA mutations and early onset inflammatory bowel disease,gut dysbiosis shows a moderate association with disease severity.
文摘This work aimed to find quantitative phenotypic traits that can be used to discriminate the levels of resistance/susceptibility to B. bovis and B. bigemina in two groups of cattle presenting the highest (H) or lowest (L) infection levels and Rhipicephalus microplus ticks count. The animals were selected from a previous study of 50 Canchim (5/8 Charolais/zebu) heifers raised in an endemic area for these parasites. These animals were evaluated regarding their TNFα, IL10, IFN-γ, IL12 and iNOS mRNA levels. No differences were found between these groups regarding TNFα, IFN-γ, IL12β or iNOS transcripts. However, the IL10 transcripts were significantly higher in the H group compared to the L group. Moreover, significant correlation coefficients were observed between B. bovis loads and both IL10 and IFN-γ transcripts, while no correlations were found for B. bigemina loads and all tested immune-related transcripts, suggesting that differential IL10 mRNA profiles were closely associated to B. bovis loads. Our results have contributed to a better understanding of the immune responses against Babesia infection, as we demonstrated that the IL10 cytokine levels might also influence or be influenced by parasitemia levels in persistently infected animals.
文摘Background Bronchiolitis is the most common infection leading to hospitalization in infancy. Interleukin-10 (IL-10) is an anti-inflammatory cytokine, and in our previous study, IL10 gene rs1800896 (-1082A/G) polymorphism was associated with viral etiology of infant bronchiolitis. The objective of this study was to evaluate the associations between IL10 single nucleotide polymorphisms (SNPs) at rs1800890 (-3575A/T), rs1800871 (-819C/T) or rs1800872 (-592C/A) either alone or combined with the SNP at rs1800896 (-1082G/A), and the etiology and severity of infant bronchiolitis. Methods Data on four IL10 SNPs were available from 135 full-term infants, hospitalized for bronchiolitis at age less than 6 months, and from 378 to 400 controls. Viral etiology was studied, and oxygen support, feeding support and the length of stay in hospital were recorded during bronchiolitis hospitalization. Results Infants with rhinovirus bronchiolitis had the IL10 rs1800890 variant AT or TT genotype less often (18.2%) than controls (63.3%, P=0.03), and likewise, had the IL10 rs1800896 variant AG or GG genotype less often (27.3%) than con-trols (65.5%, P=0.009). Twenty-eight infants with bronchiolitis had the variant–variant Grs1800896Trs1800890 haplotype, and none of them had rhinovirus infection. The IL10 rs1800871 or rs1800872 genotypes showed no associations with viruses. No association was found between any genotypes and bronchiolitis severity measures. Conclusion IL10 rs1800890 and rs1800896 polymorphisms differed between infants with rhinovirus bronchiolitis and con-trols, but not between infants with respiratory syncytial virus bronchiolitis and controls.
基金Supported by Zhejiang Province Medical Platform Backbone,No.2017KY436
文摘AIM To analyze clinical differences between monogenic and nonmonogenic very-early-onset inflammatory bowel disease(VEO-IBD) and to characterize monogenic IBD phenotypically and genotypically via genetic testing. METHODS A retrospective analysis of children aged 0 to 6 years diagnosed with VEO-IBD in a tertiary hospital in southern China from 2005 to 2017 was performed. Clinical data for VEO-IBD patients were collected, and genetic characteristics were analyzed using whole exome sequencing or target gene panel sequencing. RESULTS A total of 54 VEO-IBD patients were included in this study. A diagnosis of Crohn's disease(CD) or CDlike intestinal manifestations accounted for 72.2% of the VEO-IBD cases. Nine patients(16.7%) were identified by genetic testing as having monogenic IBD. The median age of diagnosis in the monogenic group was younger than that of the nonmonogenic IBD group, at 18 mo(interquartile range(IQR): 4 to 78) and 43.5 mo(IQR: 3 to 173), respectively; the P-value was 0.021. The incidence of perianal disease in the monogenic group was higher than that in the nonmonogenic group(P = 0.001). However, there were no significant differences between weight-forage and height-for-age Z-scores between the two groups, and similar laboratory results were obtained for the two groups. Five patients were found to have IL10 receptor mutation, two patients had chronic granulomatous disease, one patient had common variable immunodeficiency disease, and one patient had X-linked inhibitor of apoptosis protein deficiency. CONCLUSION A high proportion of monogenic IBD was observed in the VEO-IBD group, especially with disease onset before the age of 6 mo. Monogenic IBD and nonmonogenic IBD exhibited similar clinical features. Furthermore, next-generation sequencing played an important role in the diagnosis of monogenic IBD, and IL10 receptor mutation was predominant in this cohort.
