Microbial Dysbiosis Associated with Disease Severity in Treatment Naive Pediatric Patients with New-Onset Ulcerative Colitis

Abstract Despite significant evidence that the expression of several microRNA’s (miRNA) impacts on disease activity in patients with ulcerative colitis (UC), it remains unknown if the more severe disease phenotype seen in pediatric-onset UC can be explained by altered miRNA expression. In this study, we aimed to assess the relationship between miRNA expression, age, and disease severity in pediatric and adult patients with UC. Using RT-qPCR, we analyzed the expression of miR-21, miR-31, miR-126, miR-142, and miR-155 in paraffin-embedded rectum biopsies from 30 pediatric and 30 adult-onset UC patients, and found that lesions from adult patients had significantly higher expression levels of miR-21 compared to pediatric patients and that the expression levels of miR-31 (all patients) and miR-155 (pediatric patients only) correlated inversely with histological assessed disease severity. Using in situ hybridization followed by image analysis, the expression estimates of miR-21 and miR-126 were found to correlate with histological assessed disease severity. In conclusion, we found that the expression of miRNAs depends on the age of the patient and/or the severity of the disease, suggesting that miRNAs may contribute to the regulation of inflammation in UC and could be useful biomarkers in the surveillance of disease severity.

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Mucosal Expression of Type 2 and Type 17 Immune Response Genes Distinguishes Ulcerative Colitis From Colon-Only Crohn’s Disease in Treatment-Naive Pediatric Patients

Gastroenterology ◽

10.1053/j.gastro.2017.01.016 ◽

2017 ◽

Vol 152 (6) ◽

pp. 1345-1357.e7 ◽

Cited By ~ 38

Author(s):

Michael J. Rosen ◽

Rebekah Karns ◽

Jefferson E. Vallance ◽

Ramona Bezold ◽

Amanda Waddell ◽

...

Keyword(s):

Ulcerative Colitis ◽

Immune Response ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Pediatric Patients ◽

Immune Response Genes ◽

Treatment Naïve

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A256 TRENDS IN THE PREVALENCE AND SEVERITY OF ANEMIA IN PEDIATRIC PATIENTS WITH INFLAMMATORY BOWEL DISEASE IN THE LAST DECADE

Journal of the Canadian Association of Gastroenterology ◽

10.1093/jcag/gwz047.255 ◽

2020 ◽

Vol 3 (Supplement_1) ◽

pp. 133-134

Author(s):

S Geng ◽

Z Ridha ◽

L B Pham ◽

E Tran ◽

A Peixoto ◽

...

Keyword(s):

Quality Of Life ◽

Ulcerative Colitis ◽

Inflammatory Bowel Disease ◽

Disease Severity ◽

Pediatric Patients ◽

Activity Index ◽

Intestinal Involvement ◽

Inflammatory Bowel ◽

Prevalence Of Anemia

Abstract Background Anemia is one of the most common extraintestinal manifestations in patients with inflammatory bowel disease (IBD) at diagnosis. Studies have shown that anemia was associated with low levels of quality of life, which improves with the correction of anemia in adults. Recent data have shown an increase in the incidence and severity of pediatric IBD. Aims To investigate the prevalence of anemia in children at diagnosis of IBD and the trends in the past decade. The secondary aim was to investigate the associations between hemoglobin (Hb) levels and disease characteristics. Methods Eligible patients (age ≤18 years, diagnosed with IBD from 2009 to 2018) were retrospectively identified through our IBD database. Disease localization and phenotype were defined according to the Paris Classification of IBD. Anemia was defined by Hb levels according to WHO targets. The annual prevalence of anemia was calculated according to subtype (inflammatory vs iron deficiency). The Pediatric Crohn’s Disease Activity Index (PCDAI) and the Pediatric Ulcerative Colitis Activity Index (PUCAI) were used to assess the disease severity at diagnosis. Results We included 887 patients (439 females), mean (SD) age of 13.1 (3.4) years. Of these, 519 (58.5%) were identified with anemia within 30 days of diagnosis. The median (IQR) Hb level was 108 (98 -114) g/dL. Severe anemia (< 70 g/dL) was present in 1.8 % of patients. The prevalence of anemia at diagnosis remained relatively stable ranging from 60.2% in 2009 to 60.4% in 2018. The annual proportion of inflammatory vs iron-deficiency anemia is displayed in figure 1. Anemia was more prevalent in Crohn’s disease (CD) (62.2%) than Ulcerative colitis (UC) (57.9%) or IBD-unclassified (39.6%). The disease severity scores were higher in those with anemia. The median (IQR) PCDAI and PUCAI were respectively 37.5 (27.5–47.5) and 55.0 (40.0–65.0) in the anemic group as compared to 27.5 (20.0–37.50) and 35.0 (25.0–55.0) in the non-anemic group; P<0.0001. Patients with anemia had a lower BMI z-score [median (IQR) -0.84 (-1.84 - 0.08)] than the non-anemic patients [median (IQR) -0.38 (-1.21 - 0.43)]; P<0.001. The prevalence of anemia correlated significantly with disease location: upper intestinal involvement [L4a(67.7%) L4b(63.6%) L4aL4b(60.7%) none (52.8%)] P = 0.024 for CD; for UC [E1(21.1%) E2(44.4%) E3(75.0%) E4 (71.1%)] P<0.0001. A moderate correlation was found between Hb levels and C-reactive protein (r= -0.312, 95% CI: -0.378 to -0.243, P<0.0001). Conclusions Anemia remains a prevalent symptom in pediatric patients with IBD, and it is correlated with the extent of intestinal involvement and disease severity. The impact of anemia at Diagnosis and during follow-up on the levels of quality of life and physical activity is currently under investigation. Funding Agencies None

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155 Serum IL-17A in Newly Diagnosed Treatment-Naïve Ulcerative Colitis Patients Reflects Disease Severity and Predicts the Course of Disease

Gastroenterology ◽

10.1016/s0016-5085(13)60126-2 ◽

2013 ◽

Vol 144 (5) ◽

pp. S-35

Author(s):

Lena Ohman ◽

Rahil Dahlen ◽

Stefan Isaksson ◽

Asa Sjöling ◽

Mary Jo Wick ◽

...

Keyword(s):

Ulcerative Colitis ◽

Disease Severity ◽

Newly Diagnosed ◽

Course Of Disease ◽

Treatment Naïve

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DNA hypo-methylation facilitates anti-inflammatory responses in severe ulcerative colitis

PLoS ONE ◽

10.1371/journal.pone.0248905 ◽

2021 ◽

Vol 16 (4) ◽

pp. e0248905

Author(s):

Hagar Taman ◽

Christopher G. Fenton ◽

Endre Anderssen ◽

Jon Florholmen ◽

Ruth H. Paulssen

Keyword(s):

Ulcerative Colitis ◽

Dna Methylation ◽

Disease Severity ◽

Inflammatory Responses ◽

Principal Component ◽

Severe Ulcerative Colitis ◽

Inflammatory Genes ◽

Genome Wide ◽

Treatment Naïve ◽

Anti Inflammatory

Severe ulcerative colitis (UC) is a potentially life-threatening disease with a potential colorectal cancer (CRC) risk. The aim of this study was to explore the relationship between transcriptomic and genome-wide DNA methylation profiles in a well-stratified, treatment-naïve severe UC patient population in order to define specific epigenetic changes that could be responsible for the grade of disease severity. Mucosal biopsies from treatment-naïve severe UC patients (n = 8), treatment-naïve mild UC (n = 8), and healthy controls (n = 8) underwent both whole transcriptome RNA-Seq and genome-wide DNA bisulfite- sequencing, and principal component analysis (PCA), cell deconvolutions and diverse statistical methods were applied to obtain a dataset of significantly differentially expressed genes (DEGs) with correlation to DNA methylation for severe UC. DNA hypo-methylation correlated with approximately 80% of all DEGs in severe UC when compared to mild UC. Enriched pathways of annotated hypo-methylated genes revealed neutrophil degranulation, and immuno-regulatory interactions of the lymphoid system. Specifically, hypo-methylated anti-inflammatory genes found for severe UC were IL10, SIGLEC5, CD86, CLMP and members of inflammasomes NLRP3 and NLRC4. Hypo-methylation of anti-inflammatory genes during severe UC implies an interplay between the epithelium and lamina propria in order to mitigate inflammation in the gut. The specifically DNA hypo-methylated genes found for severe UC can potentially be useful biomarkers for determining disease severity and in the development of new targeted treatment strategies for severe UC patients.

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1290-P: Gut Microbiota in New-Onset Pediatric Patients with Type 1 Diabetes: Machine Learning Algorithms to Classify Microorganisms Disease-Linked

Diabetes ◽

10.2337/db20-1290-p ◽

2020 ◽

Vol 69 (Supplement 1) ◽

pp. 1290-P

Author(s):

GIUSEPPE D’ANNUNZIO ◽

ROBERTO BIASSONI ◽

MARGHERITA SQUILLARIO ◽

ELISABETTA UGOLOTTI ◽

ANNALISA BARLA ◽

...

Keyword(s):

Machine Learning ◽

Type 1 Diabetes ◽

Gut Microbiota ◽

Pediatric Patients ◽

Learning Algorithms ◽

Machine Learning Algorithms ◽

New Onset

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New-Onset Ulcerative Colitis After Kidney Transplant Immunosuppression

Consultant ◽

10.25270/con.2020.03.00009 ◽

2020 ◽

Vol 60 (3) ◽

pp. 95-96

Author(s):

We’am Hussain ◽

Drew Triplett ◽

Sangeeta Agrawal

Keyword(s):

Ulcerative Colitis ◽

Kidney Transplant ◽

New Onset

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The Frequency of HIV-1 Infection in Iranian Children and Determination of the Transmitted Drug Resistance in Treatment-Naïve Children

Current HIV Research ◽

10.2174/1570162x17666191106111211 ◽

2020 ◽

Vol 17 (6) ◽

pp. 397-407

Author(s):

Maryam Jarchi ◽

Farah Bokharaei-Salim ◽

Maryam Esghaei ◽

Seyed Jalal Kiani ◽

Fatemeh Jahanbakhsh ◽

...

Keyword(s):

Drug Resistance ◽

Pediatric Patients ◽

Phylogenetic Analyses ◽

Rna Extraction ◽

Transmitted Drug Resistance ◽

The Arts ◽

Treatment Naïve ◽

Iranian Children ◽

Hiv 1

Background: The advent of resistance-associated mutations in HIV-1 is a barrier to the success of the ARTs. Objective: In this study, the abundance of HIV-1 infection in Iranian children, and also detection of the TDR in naïve HIV-1 infected pediatric (under 12 years old) were evaluated. Materials: From June 2014 to January 2019, a total of 544 consecutive treatment-naïve HIV-1- infected individuals enrolled in this study. After RNA extraction, amplification, and sequencing of the HIV-1 pol gene, the DRM and phylogenetic analysis were successfully performed on the plasma specimens of the ART-naïve HIV-1-infected-children under 12 years old. The DRMs were recognized using the Stanford HIV Drug Resistance Database. Results: Out of the 544 evaluated treatment-naïve HIV-1-infected individuals, 15 (2.8%) cases were children under 12 years old. The phylogenetic analyses of the amplified region of pol gene indicated that all of the 15 HIV-1-infected pediatric patients were infected by CRF35_AD, and a total of 13.3% (2/15) of these children were infected with HIV-1 variants with SDRMs (one child harbored two related SDRMs [D67N, V179F], and another child had three related SDRMs [M184V, T215F, and K103N]), according to the last algorithm of the WHO. No PIs-related SDRMs were observed in HIV-1-infected children. Conclusion: The current study demonstrated that a total of 13.3% of treatment-naïve HIV-1-infected Iranian pediatrics (under 12 years old) were infected with HIV-1 variants with SDRMs. Therefore, it seems that screening to recognize resistance-associated mutations before the initiation of ARTs among Iranian children is essential for favorable medication efficacy and dependable prognosis.

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