Dataset Information

Genetic polymorphisms in Toll-like receptors among pediatric patients with renal parenchymal infections of different clinical severities.

ABSTRACT:

Background

Although several studies have suggested single gene defects or variations in the genes associated with host immune response could confer differences in susceptibility to urinary pathogen invasion, no studies have examined the genetic polymorphisms in various toll-like receptors (TLRs) that activate innate immune responses in pediatric renal parenchymal infections of different clinical severities, namely acute pyelonephritis and the clinically more severe disease, acute lobar nephronia.

Methodology

Patients who fulfilled the diagnostic criteria for acute pyelonephritis (APN) and acute lobar nephronia (ALN) without underlying diseases or structural anomalies, except for vesicoureteral reflux (VUR), were enrolled. Genotyping of the single nucleotide polymorphisms (SNPs) in the genes encoding TLR-1, TLR-2, TLR-4, TLR-5, and TLR-6 was performed by matrix-assisted laser desorption/ionization time-of-flight-based mini-sequencing analysis.

Principal findings

A total of 16 SNPs were selected for genotyping. Analysis of 96 normal and 48 patients' samples revealed that only four SNPs had heterozygosity rates >0.01. These SNPs were selected for further investigation. Hardy-Weinberg equilibrium was satisfied for the observed genotype frequencies. Statistically significant differences in the genotype frequency of TLR-2 (rs3804100, T1350C) between controls and ALN or (APN+ALN) combined group were identified using the recessive model with the correction for multiple-SNP testing. Further genotype pattern frequency analysis in TLR-2 SNPs (rs3804099 and rs3804100) showed significantly reduced occurrence of the rare allele homozygote (CC+CC) in the no-VUR subgroup of APN and ALN cases.

Conclusions

As the inflammatory responses in ALN patients are more severe than those in APN patients (higher CRP levels, longer duration of fever after antibiotic treatment), these findings suggest that the genetic variant in TLR-2 (rs3804100, T1350C) may protect the host from severe urinary tract infections as ALN.

SUBMITTER: Cheng CH

PROVIDER: S-EPMC3587587 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Genetic polymorphisms in Toll-like receptors among pediatric patients with renal parenchymal infections of different clinical severities.

Cheng Chi-Hui CH Lee Yun-Shien YS Chang Chee-Jen CJ Lin Tzou-Yien TY

PloS one 20130304 3

<h4>Background</h4>Although several studies have suggested single gene defects or variations in the genes associated with host immune response could confer differences in susceptibility to urinary pathogen invasion, no studies have examined the genetic polymorphisms in various toll-like receptors (TLRs) that activate innate immune responses in pediatric renal parenchymal infections of different clinical severities, namely acute pyelonephritis and the clinically more severe disease, acute lobar n ...[more]

PMID: 23484049

Similar Datasets

Project description:BackgroundThe pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has made widespread impact recently. We aim to investigate the clinical characteristics of COVID-19 children with different severities and allergic status.MethodsData extracted from the electronic medical records, including demographics, clinical manifestations, comorbidities, laboratory and immunological results, and radiological images of 182 hospitalized COVID-19 children, were summarized and analyzed.ResultsThe median age was 6 years, ranging from 3 days to 15 years, and there were more boys (male-female ratio about 2:1) within the studied 182 patients. Most of the children were infected by family members. Fever (43.4%) and dry cough (44.5%) were common symptoms, and gastrointestinal manifestations accounted for 11.0%, including diarrhea, abdominal discomfort, and vomiting. 71.4% had abnormal chest computed tomography (CT) scan images, and typical signs of pneumonia were ground-glass opacity and local patchy shadowing on admission. Laboratory results were mostly within normal ranges, and only a small ratio of lymphopenia (3.9%) and eosinopenia (29.5%) were observed. The majority (97.8%) of infected children were not severe, and 24 (13.2%) of them had asymptomatic infections. Compared to children without pneumonia (manifested as asymptomatic and acute upper respiratory infection), children with pneumonia were associated with higher percentages of the comorbidity history, symptoms of fever and cough, and increased levels of serum procalcitonin, alkaline phosphatase, and serum interleukins (IL)-2, IL-4, IL-6, IL-10, and TNF-α. There were no differences in treatments, duration of hospitalization, time from first positive to first negative nucleic acid testing, and outcomes between children with mild pneumonia and without pneumonia. All the hospitalized COVID-19 children had recovered except one death due to intussusception and sepsis. In 43 allergic children with COVID-19, allergic rhinitis (83.7%) was the major disease, followed by drug allergy, atopic dermatitis, food allergy, and asthma. Demographics and clinical features were not significantly different between allergic and nonallergic groups. Allergic patients showed less increase in acute phase reactants, procalcitonin, D-dimer, and aspartate aminotransferase levels compared with all patients. Immunological profiles including circulating T, B, and NK lymphocyte subsets, total immunoglobulin and complement levels, and serum cytokines did not show any difference in allergic and pneumonia groups. Neither eosinophil counts nor serum total immunoglobulin E (IgE) levels showed a significant correlation with other immunological measures, such as other immunoglobulins, complements, lymphocyte subset numbers, and serum cytokine levels.ConclusionPediatric COVID-19 patients tended to have a mild clinical course. Patients with pneumonia had higher proportion of fever and cough and increased inflammatory biomarkers than those without pneumonia. There was no difference between allergic and nonallergic COVID-19 children in disease incidence, clinical features, and laboratory and immunological findings. Allergy was not a risk factor for developing and severity of SARS-CoV-2 infection and hardly influenced the disease course of COVID-19 in children.

Project description:BackgroundWe investigated the roles of Toll-like receptors (TLRs) in naturally occurring influenza.MethodsA prospective, case - control study was conducted. Adults hospitalized with virologically confirmed influenza A infections (onset <48 hours, before treatment) were compared with age-/gender-matched controls. TLRs (2, 3, 4, 7, 8, 9) expression in monocytes and dendritic cells (DCs - total, myeloid, plasmacytoid) was quantitated using flow cytometry. Gene expression of RLRs (RIG-1, MDA-5) was evaluated using real-time PCR. Concomitant signaling molecules expression, plasma cytokine/chemokine concentrations, and respiratory tract viral loads were measured. PBMCs were cultured and stimulated ex vivo with TLR-specific ligands for cytokine responses.ResultsForty two patients with influenza (24 A/H3N2, 18 A/H1N1pdm09) and 20 controls were studied. Patients' mean age was 68 ± 16 years; 81% had respiratory/cardiovascular complications. There were increased cellular expressions of TLR9, TLR8, TLR3, and TLR7 during influenza; TLR2 and TLR4 were suppressed. Results were similar for both virus strains. Higher TLR expression levels at presentation significantly correlated with lower viral loads (Spearman's rho: -0.46 to -0.69 for TLR9, TLR8, and TLR3; P-values <0.05). Multivariate regression models (adjusted for age, comorbidity, disease severity, time from onset) confirmed their independent associations. Increased signaling molecules (phospho-MAPKs, I?B) and inflammatory cytokines (IL-6, sTNFR-1, CCL2/MCP-1; CXCL10/IP-10, IFN-?) correlated with increased TLR expression. RLRs were upregulated simultaneously. PBMCs of patients with influenza showed significant, dynamic changes in their cytokine responses upon TLR stimulation, compared with controls.ConclusionsOur results suggest that TLRs play an important role in early, innate viral inhibition in naturally occurring influenza. Inflammatory cytokine responses are concomitantly induced. These findings support investigation of TLR targeting as a novel intervention approach for prophylaxis against influenza.

Dataset Information

Genetic polymorphisms in Toll-like receptors among pediatric patients with renal parenchymal infections of different clinical severities.

Background

Methodology

Principal findings

Conclusions

Publications

Genetic polymorphisms in Toll-like receptors among pediatric patients with renal parenchymal infections of different clinical severities.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets