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

Abstract

BackgroundIn 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.MethodsA 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.ResultsAmong 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.Conclusions(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.

Analysis of 135 Cases of Pediatric Henoch-Schönlein Purpura in Gansu, Northwestern China

“…In this study, the incidence of skin purpura, arthritis, gastrointestinal and renal involvement among patients was 100%, 57.0%, 34.1% and 11.1%, respectively. The incidence of gastrointestinal and renal involvement was relatively lower compared to other Chinese studies (14,19), which might be due to regional factors. The allergens for patients were also tested.…”

“…No single unique laboratory test can be used to diagnose HSP. Several studies have reported on the relationship between laboratory markers and HSP (19,28). However, the association between these markers with disease phases and severity are not fully understood.…”

PROINFLAMMATORY CYTOKINES IL-8 AND TNFα WITH HENOCH-SCHONLEIN PURPURA IN CHILDREN

“…Our patients were found to have an increased level of IL-8 in serum, not only in the HSP group with nephritis, but also without kidney damage in comparison with the control group, the same data was obtained by French researchers. IL-8 concentrations were higher in patients with HSP WN and HSPN than in the control group [4]. Based on our results, IL-8 level may be useful as a marker for monitoring the progression of nephrotic syndrome in children with HSP.…”

“…In recent years, the question of prognostic markers of progression of HSP remains open. In particular, the IL-10 levels were determined, IgA-IgG complexes [4], IL-6, serum amyloid A [5], antistreptolysin Î, C-reactive protein, antibodies to anticardiolipin [6], (IL)-17, IL-18, IL-23 [7,8] . Many studies have identified some changes to different indicators, but no specific marker has been found.…”

Status of Complement System in Children with Henoch–Schonlein Purpura

“…Нирковий синдром спостерігається у 20-50 % хворих на ГВ та призводить до ускладнень [2]. Перехід у хронічну ниркову недостатність спостерігається у 25-30% пацієнтів, які мали нефрит внаслідок перенесеного ГВ, що призводить до інвалідизації та можливого проведення діалізного лікування пацієнтів [3] [4], IL-6, сироватковий амілоїд A [5], роль оксиду азоту (NO), цитокінів, фактору некрозу пухлин α (TNFα). У цих дослідженнях встановлено певні зміни вищеперерахованих показників, але достовірного специфічного маркеру так і не знайдено.…”