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Biomarkers identification by a combined clinical and metabonomics analysis in Henoch-Schonlein purpura nephritis children.

ABSTRACT: In children with Henoch-Schonlein purpura (HSP), the severity of Henoch-Schonlein purpura nephritis (HSPN) is considered responsible for the prognosis of HSP. The pathological process from HSP to HSPN is not clear yet and current diagnostic tools have shortcomings in accurate diagnosis of HSPN. This study aims to assess clinical characteristics of HSP and HSPN, to identify metabolic perturbations involved in HSP progress, and to combine metabolic biomarkers and clinical features into a better prediction for HSPN.A total of 162 children were recruited, including 109 HSP patients and 53 healthy children (HC). The clinical characteristics were compared between HSPN and HSP without nephritis (HSPWN). The serum metabonomics analysis was performed to determine the metabolic differences in HSP and HC.Among 109 HSP children, 57 progressed to HSPN. The increased D-dimer level was significantly associated with renal damage in HSP. The metabonomic profiles revealed alterations between various subgroups of HSP and HC, making it possible to investigate small-molecule metabolites related to the pathological process of HSP. In total, we identified 9 biomarkers for HSP vs. HC, 7 for HSPWN vs. HC, 9 for HSPN vs. HC, and 3 for HSPN vs. HSPWN.(S)-3-hydroxyisobutyric acid, p-Cresol sulfate, and 3-carboxy-4-methyl-5-pentyl-2-furanpropanoic acid were found associated with the progress of HSP to HSPN. Moreover, resulting biomarkers, when combined with D-dimer, allowed improving the HSPN prediction with high sensitivity (94.7%) and specificity (80.8%). Together these findings highlighted the strength of the combination of metabonomics and clinical analysis in the research of HSP.

SUBMITTER: Sun L

PROVIDER: S-EPMC5768399 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Biomarkers identification by a combined clinical and metabonomics analysis in Henoch-Schonlein purpura nephritis children.

Sun Lin L Xie Biao B Zhang Qiuju Q Wang Yupeng Y Wang Xinyu X Gao Bing B Liu Meina M Wang Maoqing M

Oncotarget 20171124 69

<h4>Background</h4>In children with Henoch-Schonlein purpura (HSP), the severity of Henoch-Schonlein purpura nephritis (HSPN) is considered responsible for the prognosis of HSP. The pathological process from HSP to HSPN is not clear yet and current diagnostic tools have shortcomings in accurate diagnosis of HSPN. This study aims to assess clinical characteristics of HSP and HSPN, to identify metabolic perturbations involved in HSP progress, and to combine metabolic biomarkers and clinical featur ...[more]

PMID: 29371982

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Project description:ObjectivesThe aims of the study were to identify whether left renal vein (LRV) entrapment was more prevalent in IgA nephropathy (IgAN) and Henoch-Schönlein purpura nephritis (HSPN) compared with other types of renal diseases, and the association of LRV entrapment with glomerular incidental IgA and galactose-deficient-IgA1 (Gd-IgA1) deposition.MethodsA total of 797 patients with biopsy-proven kidney diseases have been screened for LRV entrapment by color Doppler ultrasound, and the prevalence of LRV entrapment in different types of renal diseases were then analyzed. Propensity score matching analysis was used to adjust for age, gender, and body mass index. Immunostaining of Gd-IgA1 with KM55 was performed in paraffin-embedded sections of renal biopsy specimens.ResultsLRV entrapment was diagnosed in 47 patients (6%) with several kinds of renal diseases in our cohort. A total of 32 (68%) LRV entrapments were combined with expanded IgAN (idiopathic IgAN and HSPN). The prevalence of LRV entrapment in expanded IgAN was significantly higher than that in non-expanded IgAN (17 vs. 2%, p < 0.001), even after adjustment for age, gender, and body mass index by propensity score matching analysis (13 vs. 2%, p < 0.001). Removing expanded IgAN and LN, glomerular incidental IgA deposition was observed to be significantly more common in patients with LRV entrapment compared with patients without it (43 vs. 9%, p < 0.001). Furthermore, in glomerular diseases with incidental IgA deposits, significantly much larger proportion of patients with LRV entrapment were positive for glomerular Gd-IgA1 in contrast to patients without LRV entrapment (5/5 vs. 5/17, p = 0.01).ConclusionsLRV entrapment coexisted with several kinds of renal diseases, with a significantly higher prevalence in patients with idiopathic IgAN and HSPN. In patients of LN and IgAN-unrelated disease with LRV entrapment, glomerular IgA and Gd-IgA1 deposition was more common compared with patients without LRV entrapment.

Project description:ImportanceHenoch-Schönlein purpura (HSP) is the most common type of vasculitis in children. The factors that trigger the disease are poorly understood. Although several viruses and seasonal bacterial infections have been associated with HSP, differentiating the specific associations of these pathogens with the onset of HSP remains a challenge due to their overlapping seasonal patterns.ObjectiveTo analyze the role of seasonal pathogens in the epidemiology of HSP.Design, setting, and participantsThis cohort study comprised an interrupted time-series analysis of patient records from a comprehensive national hospital-based surveillance system. Children younger than 18 years hospitalized for HSP in France between January 1, 2015, and March 31, 2023, were included.ExposureImplementation and relaxation of nonpharmaceutical interventions (NPIs) for the COVID-19 pandemic, such as social distancing and mask wearing.Main outcomes and measuresThe main outcomes were the monthly incidence of HSP per 100 000 children, analyzed via a quasi-Poisson regression model, and the estimated percentage of HSP incidence potentially associated with 14 selected common seasonal pathogens over the same period.ResultsThe study included 9790 children with HSP (median age, 5 years [IQR, 4-8 years]; 5538 boys [56.4%]) and 757 110 children with the infectious diseases included in the study (median age, 0.7 years [IQR, 0.2-2 years]; 393 697 boys [52.0%]). The incidence of HSP decreased significantly after implementation of NPIs in March 2020 (-53.6%; 95% CI, -66.6% to -40.6%; P < .001) and increased significantly after the relaxation of NPIs in April 2021 (37.2%; 95% CI, 28.0%-46.3%; P < .001). The percentage of HSP incidence potentially associated with Streptococcus pneumoniae was 37.3% (95% CI, 22.3%-52.3%; P < .001), the percentage of cases associated with Streptococcus pyogenes was 25.6% (95% CI, 16.7%-34.4%; P < .001), and the percentage of cases associated with human rhino enterovirus was 17.1% (95% CI, 3.8%-30.4%; P = .01). Three sensitivity analyses found similar results.Conclusions and relevanceThis study found that significant changes in the incidence of HSP simultaneously with major shifts in circulating pathogens after NPIs for the COVID-19 pandemic indicated that approximately 60% of HSP incidence was potentially associated with pneumococcus and group A streptococcus. This finding suggests that preventive measures against these pathogens could reduce the incidence of pediatric HSP.

Dataset Information

Biomarkers identification by a combined clinical and metabonomics analysis in Henoch-Schonlein purpura nephritis children.

Publications

Biomarkers identification by a combined clinical and metabonomics analysis in Henoch-Schonlein purpura nephritis children.

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