Henoch-Schonlein Purpura Group Research Articles

Association between polymorphism at codon 469 of the ICAM-1 gene and Henoch-Schönlein purpura in an Iranian cohort

Henoch-Schönlein purpura (HSP) is a common form of IgA1-mediated blood vessel inflammation affecting mainly children. Intercellular adhesion molecule-1 (ICAM-1) gene polymorphisms have been shown to be associated with HSP in different populations; in this study, we investigated its potential association and influence on the development of severe complications in Iranian HSP patients. Twenty-three patients diagnosed with IgAV/HSP according to the criteria of the American College of Rheumatology (ACR) with 53 age- and sex-matched control subjects were referred to us. Cases and controls were genotyped using Sanger sequencing. Based on our research data, we found an association between codon 469 K/E of the ICAM1 gene and risk of HSP. Our results revealed that KK genotype and allele K are more common in control than in the HSP group, therefore the subjects with KK genotype are protected against HSP. Our data also suggested that the genotype EE is associated with higher risk of HSP progression compared to KK genotype.

Serum total bile acid levels assist in the prediction of acute intussusception with abdominal type Henoch-Schonlein purpura in children.

The severe acute abdomen associated with Henoch-Schonlein purpura (HSP) is an acute intussusception (AI). There is no reliable specific marker for AI with abdominal-type HSP. The serum total bile acid (TBA) level is a new prognostic marker associated with the severity of intestinal inflammation. The purpose of this study was to identify the prognostic value of serum TBA levels for the diagnosis of AI in children with abdominal-type HSP. A retrospective study of 708 patients with abdominal-type HSP was conducted, with demographic data, clinical symptoms, hepatic function index, immune function markers, and clinical outcomes assessed. Patients were divided into two groups: HSP (613 patients) and HSP with AI (95 patients). The data were analysed using SPSS 22.0. Of the 708 patients, the serum TBA levels were higher in the HSP with AI group than in the HSP group (P < 0.05). Logistic regression analysis showed that vomiting (OR = 396.492, 95% CI = 14.93-10,529.67, P < 0.001), haematochezia (OR = 87.436, 95% CI = 5.944-1,286.214, P = 0.001), TBA (OR = 16.287, 95% CI = 4.83-54.922, P < 0.001), and D-dimer (OR = 5.987, 95% CI = 1.892-15.834, P = 0.003) were independent risk factors for abdominal-type HSP with AI. Receiver operating characteristic (ROC) curve analysis showed that the optimal cut-off serum TBA value (sensitivity = 91.58%, specificity = 84.67%, AUC = 93.6524%) was >3 μmol/L for predicting AI in children with abdominal-type HSP. In this group of HSP patients with AI, a serum TBA level ≥6.98 μmol/L was significantly associated with an increased incidence of operative treatment (51.85% vs. 75.61%, P = 0.0181), intestinal necrosis (9.26% vs. 29.27%, P = 0.0117), and length of hospital stay [15.76 ± 5.31 vs. 10.98 ± 2.83 (days), P < 0.0001]. In children with HSP and AI, the serum TBA level was significantly higher. A novel but promising haematological indicator, the serum TBA level, helps identify HSP with and without AI and predicts intestinal necrosis in HSP with AI.

Serum levels of degraded monosaccharides in children with Henoch-Schönlein purpura.

To examine the serum levels of degraded monosaccharides in children with Henoch-Schönlein purpura (HSP) and to study the clinical significance of degraded monosaccharides in HSP. A prospective analysis was performed on 132 children who were diagnosed with HSP from September 2019 to January 2022, and 132 healthy children were enrolled as the control group. High-performance liquid chromatography was used to determine the content of degraded monosaccharides in serum in both groups. The receiver operating characteristic (ROC) curve was used to evaluate the efficiency of degraded monosaccharides for the diagnosis of HSP. Compared with the control group, the HSP group had significantly higher serum levels of mannose, glucosamine, aminogalactose, and galactose (P<0.001). The four degraded monosaccharides had an area under the ROC curve of 0.919, 0.913, 0.832, and 0.932 respectively for the diagnosis of HSP (P<0.05). Children with HSP have higher serum levels of mannose, glucosamine, aminogalactose, and galactose than the healthy population. The levels of degraded monosaccharides may have an important value for the diagnosis of HSP.

Integrated Analyses of Gut Microbiome and Host Metabolome in Children With Henoch-Schönlein Purpura.

Recent studies have shown that intestinal microbes and metabolites are involved in the pathogenesis of many diseases. However, whether and how they are related to Henoch–Schönlein purpura (HSP) has yet to be understood. This work is designed to detect gut microbes, intestinal and serum metabolites in children with HSP, trying to discover the etiology and pathogenesis of HSP. A total of 86 children were recruited in this study, namely, 58 children with HSP (HSP group) and 28 healthy children as control groups (CON group). 16S rDNA amplicon sequencing technology and UPLC-QTOF/MS non-targeted metabolomics analysis were used to detect the intestinal microbes and metabolites, and also multi-reaction monitoring technology for detecting serum arachidonic acid (AA) and its metabolites. Then, correlation analysis was performed to explore the possible interaction between the differential gut microbes and metabolites. As a result, at the microbiota family level, the CON group had an advantage of Coriobacteriaceae while the HSP group had a dominant Bacteroidaceae. Five kinds of bacteria in the HSP group were significantly enriched at the genus level, and seven kinds of bacteria were significantly enriched in the CON group. A total of 59 kinds of gut metabolites significantly differ between the two groups, in which most are lipids and peptides. Spearman correlation analysis showed that Bacteroides, Dialister, and Agathobacter were associated with unsaturated fatty acids, especially AA metabolism. Then, we tested the AA related metabolites in serum and found thromboxane B2, leukotriene B4, prostaglandin D2, 9S-hydroxyoctadecadienoic acid, and 13S-hydroxyoctadecadienoic acid significantly changed. In conclusion, children with HSP had dominant Bacteroidaceae and decreased Coriobacteriaceae in the family level of gut microbes, and also lipids and peptides changed most in the gut metabolites. Our data suggested that the biosynthesis and metabolism of unsaturated fatty acids, especially AA and its metabolites, might participate in the occurrence and development of HSP.

Correlations of Leukotriene B4 and 25-Hydroxyvitamin D3 Levels with Disease Severity in Children with Henoch-Schonlein Purpura.

The aim was to explore the correlations of leukotriene B4 (LTB4) and 25-hydroxyvitamin D3 [25(OH)D3] levels with disease severity in children with Henoch-Schonlein purpura (HSP). A total of 260 HSP children admitted from January 2017 to December 2018 were selected, and 60 healthy children physically examined in the same period were enrolled as controls. The results of general laboratory tests and expression levels of leukotriene B4 (LTB4) and 25-hydroxyvitamin D3 [25(OH)D3] were compared. The correlations of LTB4 and 25(OH)D3 with immunoglobulin A (IgA) were statistically analyzed, and the expression levels of LTB4 and 25(OH)D3 were compared between Henoch-Schonlein purpura nephritis (HSPN) group and non-Henoch-Schonlein purpura nephritis (NHSPN) group. The optimal cutoff values of LTB4 and 25(OH)D3 to predict HSP were analyzed by receiver operating characteristic (ROC) curves, based on which they were divided into low-, intermediate-, and high-risk groups. The length of hospital stay and recurrence rate within 6 months were compared. The levels of white blood cell count, platelets, C-reactive protein, IgA, IgM, IgE, complement C3, and LTB4 were significantly higher and 25(OH)D3 was lower in HSP group than those in control group (p < 0.05). IgA, LTB4, and 25(OH)D3 levels were independent risk factors for HSP (p < 0.05). LTB4 was positively correlated with IgA (p < 0.05), and 25(OH)D3 was negatively correlated with IgA (p < 0.05). LTB4 level was significantly higher and 25(OH)D3 level was lower in HSPN group than those in NHSPN group (p < 0.05). The optimal cutoff values of LTB4 and 25(OH)D3 were 27.82 pg/mL and 22.10 ng/mL, respectively, the length of hospital stay gradually increased in low-, intermediate-, and high-risk groups, and the recurrence rates within 6 months were 14.2%, 31.5%, and 39.6%, respectively (p < 0.05). LTB4 level increases and 25(OH)D3 level decreases in children with HSP, and the expression levels are significantly correlated with disease severity, suggesting predictive values for prognosis.

Association between Tfh and PGA in children with Henoch-Schönlein purpura.

ObjectiveThe aim of this study was to investigate the roles of follicular helper CD4+ T cells (Tfh) and serum anti-α-1,4-d-polygalacturonic acid (PGA) antibody in the pathogenesis of Henoch–Schönlein purpura (HSP).MethodsELISA was performed to determine serum PGA-IgA and PGA-IgG. Flow cytometry was utilized to determine the peripheral CD4+ CXCR5+ and CD4+ CXCR5+ ICOS+ Tfh cells. Real-time PCR was conducted to determine the expression of Bcl-6 gene. Then the change of Tfh cells was analyzed, together with the association with the anti-PGA antibody as well as the roles in the pathogenesis of HSP.ResultsCompared with the cases with acute respiratory infection and elective surgery, the proportion of CD4+ CXCR5+ and CD4+ CXCR5+ ICOS+ Tfh cells in the HSP group showed significant elevation (P < 0.001). A significant correlation was noticed between PGA-IgA and CD4+ CXCR5+ Tfh cells (r = 0.380 and P = 0.042) and CD4+ CXCR5+ ICOS+ Tfh cells (r = 0.906 and P < 0.001). The expression of Bcl-6 in the HSP group showed no statistical difference compared with that in the acute respiratory infection and the surgery control (P < 0.05).ConclusionIncreased activity of Tfh cells, which is closely related to mucosal immunity, may be a major contributor in the elevation of PGA-IgA, and Tfh cells and PGA-IgA are closely related to the occurrence of HSP.

Differences in Manifestations and Gut Microbiota Composition Between Patients With Different Henoch-Schonlein Purpura Phenotypes.

BackgroundGut microbiota plays an important role in the pathogenesis of immune-mediated diseases. However, the complex pathogenesis of Henoch-Schonlein Purpura (HSP) remains elusive. This study aimed to characterize the gut microbiota in HSP patients and explore the potential association between gut microbiota composition and phenotypic changes in HSP.Methods16SrRNA gene sequencing and bioinformatic analyses were performed using total DNA extracted from the fecal microbiota of 34 children with HSP, including 18 primary cases, 16 recurrent cases, and 23 healthy children.ResultsThe diversity indexes showed significant differences in the microbial community among the primary HSP groups, the recurrent HSP group and healthy controls. The abundance of Escherichia-Shigella in the recurrent HSP group was significantly higher than that in the primary HSP group, and the constructed ROC curve had an AUC value of 0.750. According to the Spearman correlation analysis, the abundance of Bacteroides was positively associated with the serum IgG level in children with HSP, while the abundance of Lachnoclostridium was negatively correlated with the complement component 3 (C3). The diversity indexes of gut microbiota in the HSP group with abdominal symptoms were higher than those in the HSP group without GI involvement, and also higher than those in the healthy control group. In the HSP group with GI involvement, the abundance of Faecalibacterium was decreased, while the abundance of Streptococcus and Fusobacteria was increased, compared to the HSP group without GI involvement.ConclusionsThe gut microbiota of children with HSP was different from that of healthy children. The genus Escherichia-Shigella has a diagnostic value for HSP recurrence. Bacteroides and Lachnoclostridium may affect IgG and complement C3 levels in children with HSP. Abdominal symptoms in HSP children were related to gut microbiota (Streptococcus and butyric acid-producing bacteria).

Abnormalities of Serum Fatty Acids in Children With Henoch-Schönlein Purpura by GC-MS Analysis.

Purpose: The objectives of this work were to test the levels of serum medium- and long- chain fatty acids (MLCFAs) in children and to discover their possible relationship with Henoch-Schönlein Purpura (HSP), also known as Immunoglobulin A vasculitis.Methods: A total of 57 children with HSP (HSP group) and 28 healthy children (CON group) were recruited for this study. Serum specimens were collected to detect the compositions and contents of MLCFAs by gas chromatography with mass spectrometry (GC-MS) analysis.Results: The contents of all detected 37 MLCFAs in the HSP group were higher than the healthy group. Thirty-one species of MLCFAs were discovered to have a significant difference (p < 0.05) in two groups. Comparing to healthy controls, there were 31, 31, 18 fatty acids showed a statistical difference in the untreated group, regular treated group, and withdrawal group of HSP, respectively. The trend of fatty acids in the three HSP groups was similar to the healthy controls, as well as the untreated group and regular treated group changed more obviously than the withdrawal group. Almitate (C16:0) and 18 carbon atoms (C18) of fatty acids were abundant in all three HSP groups, divided according to the treatment of glucocorticoid. Some fatty acids were found having considerable differences (p < 0.05) in three groups. Monounsaturated fatty acids (MUFAs), including elaidate (C18:1T), cis-11,14,17-eicosatrienoic acid ester (C20:1), and cis-15-tetracosenoate (C24:1), were distinctly higher in HSP children with renal damage.Conclusion: Our study revealed that the abnormalities in MLCFA may be associated with the development of HSP. Another interesting finding was that fatty acids contents were changing during the glucocorticoid treatment. Meanwhile, long-chain MUFAs may have an impact on renal damage in HSP patients. Further studies need to be carried out in order to explore the specific mechanism of fatty acids in the course of HSP.

Effects of IL-27 on Th17 Cells in Patients with Henoch-Schönlein Purpura

To investigate the effect of IL-27 on Th17 cells in patients with henoch-schönlein purpura（HSP） in order to further elucidate the pathogenesis. Fifty patients with HSP treated in our hospital from April 2019 to July 2019 were selected as HSP group, and 30 volunteers underwent physical examination at the same time were selected as control group. The proportion of Th17 cells in peripheral blood of HSP group and healthy control group was determined by flow cytometry (FCM). A total of 27 HSP patients were selected, and candidate peripheral blood mononuclear lymphocytes (PBMC) were co-cultured with exogenous rhIL-27, and the ratio of Th17 cells was detected by flow cytometry. The proportion of Th17 cells in the peripheral blood of HSP patients with acute phase was (1.57±0.54)%, which was significantly higher than that of the control group (0.86±0.40)% (t=-6.298, P<0.001), and the proportion of Th17 cells was decreased significantly after rhIL-27 co-culture (1.39%±0.52% vs 0.98%±0.44%)(P<0.05). IL-27 can reduce the level of Th17 cells in patients with HSP, which may be involved in the pathogenic process of HSP and play a protective role in the development of the disease.

Changes of coagulation and fibrinolysis system in children with Henoch-Schonlein purpura nephritis and its clinical significance

Objective To investigate the changes of coagulation and fibrinolysis system in children with Henoch-Schonlein purpura nephritis and its clinical significance. Methods From January 2013 to December 2016, 73 children with Henoch-Schonlein purpura inthe First People's Hospital of Huzhouwere selected as the Henoch-Schonlein purpura group, 73 children with Henoch-Schonlein purpura nephritis were selected as the Henoch-Schonlein purpura nephritis group, and 73 healthy children were selected as the control group.Antithrombin III activity (AT III), fibrinogen degradation products (FDP), plasma D-dimer (D-D), prothrombin activator inhibitor-1 (PAI-1), tissue plasminogen activator (t-PA), fibrinogen (FIB) levels and 24-hour urinary protein excretion were measured in three groups. Results The levels of FIB, AT III%, FDP, D-D, PAI-1 and t-PA in the Henoch-Schonlein purpura group and the Henoch-Schonlein purpura nephritis group[(2.89±0.76)g/L, (3.51±0.81)g/L; (145.72±8.46)%, (163.24±9.05)%; (1.31±0.67)mg/L, (1.54±0.72)mg/L; (0.87±0.52)mg/L, (1.18±0.67)mg/L; (66.47±2.58)ng/L, (91.02±3.24)ng/L; (16.34±0.98)μg/L, (12.35±1.06)μg/L]were higher than those in the control group[(1.88±0.54)g/L, (119.48±8.92)%, (0.92±0.33)mg/L, (0.32±0.18)mg/L, (31.25±3.02)ng/L, (6.82±0.75)μg/L](t=9.256, 18.236, 4.462, 8.540, 75.760, 65.912; 14.306, 29.423, 6.688, 10.591, 115.297, 36.387, all P 0.05). The 24-hour urinary protein excretion was positively correlated with AT III%, FDP, D-D and IL-33 in patients with Henoch-Schonlein purpura nephritis (r=0.502, 0.546, 0.483, all P 0.05). Conclusion Patients with purpuric nephritis are in a state of hypercoagulability and hyperfibrinolysis, and coagulation and fibrinolysis disorders are closely related to renal damage in patients. Key words: Purpura, Henoch-Schonlein; Nephritis; Antithrombin III activity; Fibrinogen degradation products; Plasma D dimer

Association between anti-α-1,4-D-polygalacturonic acid antibodies and Henoch-Schönlein purpura in children.

ObjectiveTo investigate the relationship between anti-α-1,4-D-polygalacturonic acid (PGA) antibodies, particularly immunoglobulin (Ig)A, and Henoch-Schönlein purpura (HSP) in children.MethodsThis observational case–control study investigated PGA-IgA, PGA-IgG, and PGA/PGA-IgA circulating immune complex (PGA/PGA-IgA CIC) in paediatric patients with HSP versus controls. Children with HSP were also evaluated for food specific IgG and food intolerance. Between-group differences in anti-PGA antibodies were analysed.ResultsSerum PGA-IgA and PGA-IgG levels were significantly increased in patients with acute HSP (n = 251) versus those with urticaria (n = 48), acute respiratory infections (n = 95), surgical controls (n = 53) and neonates (n = 92). PGA/PGA-IgA CIC levels were also significantly higher in the acute HSP group versus surgical control and neonate groups. Levels of PGA/PGA-IgA CIC and PGA-IgA were significantly correlated (r = 0.997), and PGA-IgA showed high diagnostic specificity for HSP. No statistically significant differences were observed in PGA-IgA and PGA-IgG between various degrees of food intolerance in children with HSP.ConclusionIncreased anti-PGA antibodies, particularly PGA-IgA and PGA/PGA-IgA CIC, were significantly associated with acute HSP in children. Food intolerance was not found to be associated with increased anti-PGA antibodies in children with HSP.

DNA methylation status of the forkhead box protein 3 gene in CD4+ T cells of patients with Henoch-Schönlein purpura and its correlation with regulatory T cells

Objective To determine the proportion of CD4+CD25+ regulatory T (Treg) cells, mRNA expression of the forkhead box protein 3 (Foxp3) gene, and DNA methylation status of the Foxp3 promoter in peripheral CD4+ T cells from patients with Henoch-Schonlein purpura. Methods Totally, 20 inpatients with Henoch-Schonlein purpura and 20 healthy controls were enrolled from Department of Dermatology, the Second Xiangya Hospital of Central South University between 2015 and 2016, and there were no significant differences in the gender and age between the two groups (both P > 0.05) . CD4+ T cells were isolated from the peripheral blood samples of these subjects. Real-time fluorescence-based quantitative PCR was performed to detect the mRNA expression of the Foxp3 gene, flow cytometry to determine the proportion of CD4+CD25+ Treg cells, and sodium bisulfite sequencing PCR (BSP) to determine the DNA methylation status of the Foxp3 promoter. Statistical analysis was carried out with SPSS16.0 software by using two-sample t test for the comparison between the two groups, and linear correlation analysis for evaluating the correlations of the DNA methylation status of the Foxp3 promoter with clinical severity scores and the proportion of CD4+CD25+ Treg cells. Results Compared with the healthy control group, the Henoch-Schonlein purpura group showed significantly decreased mRNA expression of the Foxp3 gene in CD4+ T cells (0.380 ± 0.226 vs. 1, t = 9.503, P < 0.01) , proportion of CD4+CD25+ Treg cells (1.668% ± 0.959% vs. 2.741% ± 1.131%, t = 2.552, P < 0.05) , but significantly increased DNA methylation status of the Foxp3 promoter (0.712 ± 0.164 vs. 0.453 ± 0.147, t = 3.610, P < 0.01) . In the Henoch-Schonlein purpura group, the DNA methylation status of the Foxp3 promoter was negatively correlated with the percentage of CD4+CD25+ Treg cells (r = -0.490, P < 0.05) , but positively correlated with the clinical severity scores (r = 0.486, P < 0.05) . The DNA methylation level of the Foxp3 promoter was significantly higher in the patients with renal impairment than in those without renal impairment (P < 0.05) . Conclusion The patients with Henoch-Schonlein purpura showed increased DNA methylation status of the Foxp3 promoter in CD4+ T cells, decreased mRNA expression of the Foxp3 gene and proportion of CD4+CD25+ Treg cells, which may be related to the occurrence of Henoch-Schonlein purpura, and affect disease development and prognosis. Key words: Purpura, Schoenlein-Henoch; T-lymphocytes, regulatory; DNA methylation; Genes, Foxp3

Role of hypomethylation of suppressor of cytokine signaling in T helper 17 cell/regulatory T cell imbalance in children with Henoch-Schönlein purpura

To investigate the association between suppressor of cytokine signaling (SOCS) hypomethylation and T helper 17 (Th17) cell/regulatory T (Treg) cell imbalance in children with Henoch-Schönlein purpura (HSP) and the immune pathogenesis of HSP. A total of 32 children in the acute stage of HSP who were hospitalized from May 2014 to January 2015 were enrolled as subjects, and 28 children who underwent physical examination were enrolled as normal control group. ELISA was used to measure the plasma level of interleukin-6 (IL-6). Flow cytometry was used to measure the percentages of CD4+ IL-17A+ T cells (Th17 cells) and CD4+CD25+ Treg cells (Treg cells) in peripheral blood and mean fluorescence intensity (MFI) for phosphorylated-STAT3 (pSTAT3) protein in CD4+ T cells. Quantitative real-time PCR was used to measure the mRNA expression of suppressor of cytokine signaling-1 (SOCS1) and suppressor of cytokine signaling-3 (SOCS3) in CD4+ T cells. High-resolution melting (HRM) was used to evaluate the methylation level of the CpG islands in SOCS1 exon 2 and the CpG islands of the potential bind sites for STAT3 in the 5'-untranslated region (5'-UTR) of SOCS3 in peripheral blood mononucleated cells. Compared with the normal control group, the HSP group had significant increases in plasma IL-6 concentration and MFI for pSTAT3 in CD4+ T cells, as well as a significant increase in the percentage of Th17 cells and a significant reduction in the percentage of Treg cells (P<0.05). The HSP group had significantly higher mRNA expression of SOCS1 and SOCS3 in peripheral blood mononucleated cells than the normal control group (P<0.05). In the HSP group, the mRNA expression of SOCS1 and SOCS3 was negatively correlated with Th17/Treg ratio (P<0.05). The HSP group had hypomethylation of the CpG islands in SOCS1 exon 2 and the potential binding site for STAT3 in SOCS3 5'-UTR, while the normal control group had complete demethylation. Low relative expression of SOCS1 and SOCS3 caused by hypomethylation may be a factor for Th17/Treg imbalance in children with HSP.

High-Mobility Group Protein Box 1 is Upregulated in Children with Henoch-Schonlein Purpura

Henoch-Schonlein purpura (HSP) is a common systemic vasculitis in children. High-mobility group protein box 1 (HMGB1) is an inflammatory cytokine involved in many autoimmune diseases. This study aimed to examine the expression of HMGB1 in HSP. Fifty-six children with HSP (HSP group) and 32 healthy children (Control group) were enrolled, and their clinic data were collected. Real-time polymerase chain reaction was used to detect mRNA levels of HMGB1, Toll-like receptor 2 (TLR2), TLR4, receptor of advanced glycation end products (RAGE), and nuclear factor-κB (NF-κB) in peripheral blood mononuclear cells (PBMCs). Enzyme-linked immunosorbent assay was used to detect serum levels of HMGB1, interleukin-6 (IL-6), IL-8, and tumor necrosis factor-α (TNF-α). The mRNA levels of HMGB1, TLR2, TLR4, and NF-κB in PBMCs were upregulated in HSP group with kidney injury compared with control group without kidney injury (P < 0.05). The serum levels of HMGB1, IL-6, IL-8, and TNF-α in HSP group with kidney injury were signifi...

Serum and Urinary Resistin Levels in Henoch Schonlein Purpura

Background: Henoch Schonlein Purpura (HSP) is one of the most common vasculitic diseases of childhood. Considering the effects of resistin in inflammation, we hypothesized that resistin was important in the pathogenesis of HSP. Therefore, the aim of this study was to investigate the serum and urinary resistin levels of patients with HSP and compare them with those of healthy subjects. Materials and Methods: The study was performed between March 2015 and September 2015 at University of Health Sciences, Umraniye Training and Research Hospital, Department of Pediatrics. Fifteen children with HSP were evaluated during the acute phase and compared with fifteen healthy age- and sex-matched controls. Results: A total of 30 children, 15 of whom were in the HSP group participated in the study. There were fifteen children with a median age of 8.65 ± 4.35 years in the HSP group, of whom 9 (60%) were male and 6 (40%) were female. In the control group, there were 15 children with 6 (60%) males and 4 (40%) females, aged 3 to 16 years. The serum resistin level of the HSP group (53.96 ± 33.61 ng/ml) was significantly higher than that of the control group (19.46 ± 4.42 ng/ml) (P < 0.001). Similarly, the mean urinary resistin level of the patients in the HSP group (116,36 ± 69,54 ng/ml) was significantly higher than that in the control group (29,39 ± 29,66 ng/ml) (P < 0.001). In the HSP group there was no correlation between mean serum resistin level and CRP, WBC (r = 0.038, P = 0.892 and r = 0.236, P = 0.343, respectively). No statistically significant difference was observed with respect to the presence of arthritis (P = 0.439). Conclusions: The effects of resistin in vasculitic disorders have not been clearly demonstrated so far. In our study serum and urinary resistin levels were significantly higher in patients with acute stage of HSP than that in the healthy control group. According to our results, serum and urinary resistin levels could be used as a diagnostic or prognostic marker and be considered as a secondary epiphenomenon in children with HSP.Further studies are warranted to elucidate the pathogenic mechanisms by which serum and urinary resistin levels elevate in HSP patients with kidney involvement and relapses.

Effect of neutrophils and their IgA Fc receptor on vascular endothelial cell apoptosis in patients with Henoch-Schönlein purpura and its mechanism

Objective To investigate the role of neutrophils and their IgA Fc receptor CD89 in the occurrence of Henoch-Schonlein purpura (HSP) , to evaluate their effects on vascular endothelial cell apoptosis, and to explore their mechanisms. Methods Peripheral blood neutrophils were isolated from 30 children with acute HSP and 9 age-matched healthy controls separately. After isolation of serum IgA by Jacalin affinity chromatography, IgA was purified by polypropylene dextran gel chromatography. Real-time fluorescence-based quantitative PCR (qPCR) and Western blot analysis were performed to determine the mRNA and protein expression of CD89 on neutrophils respectively, and flow cytometry was conducted to measure the expression of neutrophil activation marker CD11b. Human umbilical vein endothelial cells (HUVEC) were co-cultured with neutrophils isolated from patients with HSP (HSP group) and healthy controls (healthy control group) separately. Moreover, the HSP group were divided into 3 subgroups to be treated with serum IgA isolated from the HSP patients (HSP IgA group) , monomeric IgA (mIgA group) and phosphate-buffered saline (blank control group) respectively. Then, flow cytometry was conducted to detect apoptosis of co-cultured HUVEC, and enzyme-linked immunosorbent assay (ELISA) to measure levels of interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-α) in the supernatant of co-cultured cells. Results There was no significant difference in the mRNA expression of CD89 on neutrophils between the patients with HSP and healthy controls (P = 0.98) , but the protein expression of CD89 was significantly lower in the patients with HSP than in the healthy controls (0.60 ± 0.16 vs. 0.83 ± 0.24, P = 0.03) . The expression of CD11b on neutrophils was significantly higher in the patients with HSP than in the healthy controls (1 880.25 ± 388.29 vs. 1 109.25 ± 364.25, P < 0.01) . The apoptosis rate of co-cultured HUVEC was also significantly higher in the HSP group than in the healthy control group (37.44% ± 5.49% vs. 17.14% ± 4.45%, P < 0.01) . In addition, the HSP IgA group showed significantly higher apoptosis rate of co-cultured HUVEC and levels of IL-8 and TNF-α in the supernatant compared with the mIgA group (all P < 0.01) and blank control group (P < 0.01, = 0.01, = 0.02, respectively) . Conclusions Peripheral blood neutrophils in patients with HSP are activated, which can induce the apoptosis of vascular endothelial cells. HSP IgA can promote the neutrophil-mediated apoptosis of vascular endothelial cells and secretion of IL-8 and TNF-α, while mIgA may show a certain inhibitory effects. Key words: Purpura, Schoenlein-Henoch; Immunoglobulin A; Receptors, Fc; Neutrophils; Human umbilical vein endothelial cells; Apoptosis; Interleukin-8; Tumor necrosis factor-alpha

The relationship between red cell distribution width and the risk of Henoch–Schönlein purpura nephritis

Introduction: Red blood cell distribution width (RDW) is elevated in various inflammatory diseases, but its clinical significance in Henoch–Schönlein purpura nephritis (HSPN) in unknown. The aim of this study was to determine the value of RDW as a risk factor or marker for HSPN in children.Methods: This was a case-control study of 105 Henoch–Schönlein purpura (HSP) patients, 120 HSPN patients and 192 healthy controls. The relationship between RDW-coefficient of variation (RDW-CV) and the clinical characteristics of HSPN patients was determined by a multiple logistic regression analysis (MVLRA). Receiver operating characteristic (ROC) curves were applied to compare the diagnostic potential of the RDW-CV, a panel of routine markers and combinations of these indices.Results: The RDW-CV values were significantly higher in the HSPN group than the HSP group and controls (P < 0.001). Significant correlations were found between RDW-CV and ESR (P = 0.001). A combination of RDW-CV and ESR in a ROC curve showed 80% sensitivity and 84.9% specificity in the HSP patients, and 85.8% sensitivity and 93.8% specificity in the HSPN patients. The MVLRA revealed that RDW-CV (OR 1.69, 95% CI 1.16–2.48, P = 0.007) was an independent predictor of HSPN.Conclusions: The RDW levels were highest in the HPSN group, suggesting that RDW, especially the combination of RDW and ESR, may have value when assessing the risk of HSPN.

Elevated urinary monocyte chemoattractant protein-1 levels in children with Henoch-Schonlein purpura nephritis

Chemokine monocyte chemoattractant protein-1 (MCP-1) has been proved as a potential urinary biomarker in nephropathies. The aim of this study was to investigate the urinary monocyte chemoattractant protein-1 (MCP-1) levels and clinical significance in Henoch-Schonlein purpura (HSP) children with and without nephritis and determine the association of MCP-1 with proteinuria. A total of 261 HSP children-with or without nephritis-and 84 healthy control children were enrolled in this study. Of these, 126 HSP nephritis (HSPN) children were subdivided into three groups according to total urine protein in 24h (TUP): Group A, mild proteinuria group with TUP <25mg/kg; Group B, moderate proteinuria group with TUP ≥25mg/kg and <50mg/kg; Group C, severe proteinuria group with TUP ≥50mg/kg. Urinary MCP-1 levels were determined by ELISA. Levels of serum creatinine (Cr), blood urea nitrogen (BUN), urinary α1-micro globulin (α1-MG), micro-albumin (mAlb), immunoglobulin G (IgG), transferrin (TRF) and TUP were performed to determine their associations with MCP-1. Urinary MCP-1 was significantly higher in HSPN group in comparison with HSP group and controls (P<0.05), but no significant difference was found between the HSP group and the healthy group (P>0.05). The levels of urinary MCP-1 increased in parallel to the enhancement of total urine protein in 24h in HSPN patients. There were statistically significant differences among these three groups of HSPN children (p<0.05). Urinary MCP-1 correlated positively with urinary α1-MG, mAlb, IgG, TRF and TUP in HSPN, whereas no correlation was observed with serum Cr and BUN. MCP-1 was elevated in children with HSPN and correlated with proteinuria. Urinary MCP-1 could be used as a suitable, non-invasive biomarker to provide valuable information not only for the diagnosis of HSPN, but also for evaluation of severity of renal damage.

Association between red blood cell distribution width and Henoch-Schonlein purpura nephritis.

To investigate whether red blood cell distribution width (RDW) is a marker of the risk of Henoch–Schonlein purpura (HSP) nephritis (HSPN), a total of 669 HSP patients and 168 healthy controls were included in this retrospective study. Two hundred fifty-six (38.3%) of the patients had kidney involvement. Compared with the HSP group, RDW was significantly higher in the HSPN group (P < .001). Binary logistic regression identified that HSPN was independently associated with age, RDW, platelet, and total cholesterol (odds ratio = 1.409, 1.353, 0.996, and 2.019, respectively). In addition, RDW values of HSPN patients with crescents on histopathology (classes III, IV, and V) were higher compared with those of HSPN without crescents (classes I and II) (P = .019). The receiver–operating characteristic curve analysis showed that the RDW at a cut-off point of 13.25 has 61% sensitivity and 79% specificity in predicting the presence of crescents on histopathology. It was first shown that RDW levels in HSPN are significantly higher than those in HSP without nephritis and healthy controls. RDW can be an independent predictor of HSPN and its levels greater than 13.25 were useful in the predicting the presence of crescents on histopathology.

IL-33 and sST2 levels in Serum of Children with Henoch-Schnlein Purpura and Their Clinical Significance

To investigate the serum IL-33 and sST2 levels in children with Henoch-Schonlein purpura (HSP), and explore their clinical significance. Total 27 HSP patients and 22 healthy controls were enrolled in present study. The expressions of IL-33 and sST2 were measured by enzyme linked immunosorbent assay (ELISA). Using real-time quantitative polymerase chain reaction (RT-PCR), the mRNA expression of IL-33 and sST2 were detected in all subjects. The level of the IL-33 in the serum of HSP group and control group was 365.5±160.6 pg/ml and 175.9±92.8 pg/ml(P< 0.05). The level of the sST2 was increased in the serum of HSP group (1788.6±523.8 pg/ml) as compared with that in control group (1083.6±489.6 pg/ml)(P>0.05), but the ratio of sST2/IL-33 in HSP patients was much lower than that in the controls(P<0.05), IL-33 and sST2 mRNA levels were up-regulated in HSP patients by 5.47±1.97-fold(P<0.05) and 3.13±2.01-fold(P<0.05) compared with controls, but sST2/IL-33 significantly decreased in HSP patients(P<0.05). The levels of IL-33 and sST2 increase in the serum of HSP patients, but the ratio of sST2/IL-33 is much lower than that in control.