Development Of Henoch-Schönlein Purpura Research Articles

Oral microbiota imbalance: A predisposing factor for Henoch-Schönlein Purpura in children

Oral microecological dysregulation has been shown to be associated with various immune system disorders. Henoch-schonlein purpura (HSP) is an autoimmune small vessel inflammatory disease in children of uncertain etiology, and studies have suggested that streptococcal infection may be an influential factor in its development. However, the relationship between oral microecological dysregulation and HSP has not been clearly studied so far. In this study, an epidemiological survey on the oral health status of children with HSP was investigated in this paper, and collected dental plaque from four groups of children for 16SrDNA high-throughput sequencing to analyze the composition and changes of oral microbial diversity among different groups. The results showed that the oral health status of children with HSP was poor, except for the incidence of caries in the 5-year-old group, the caries rate and dmfs/DMFS in the 3,4 and 5-year-old groups were higher than the same age in the fourth Chinese Oral Health Epidemiological Survey. Moreover, the development of HSP is accompanied by disturbances in the oral microbiota; a decrease in the number of Firmicutes which producing butyric acid may be closely associated with the development of HSP; changes in the abundance of Streptococcus and Neisseria may be a risk factor for the development 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.

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.

Follicular helper T (Tfh) cells involves in the pathogenesis of Henoch-Schönlein purpura through affecting CD40/CD40L axis

Objective To investigate whether follicular helper T (Tfh) cells were involved in the development of Henoch-Schonlein purpura (HSP) and Henoch-Schonlein purpura nephritis (HSPN) in children through affecting CD40/CD40L axis. Methods Fifty-five subjects were enrolled in this study and divided into four groups as follows: 22 children with HSP but without renal involvement (Group A), 11 children with HSPN presenting with microhematuria (Group B), 11 children with HSPN presenting with microhematuria and proteinuria (Group C) and 11 healthy children (control group). Flow cytometry was performed to detect the percentages of CD19+ B cells and their subsets, CD19+ B cells and CD19+ CD38+ B cells secreting different Ig classes, CD19+ CD40+ B cells and their subsets and Tfh cells expressing CD40 ligand (CD40L). Results Compared with the control group, the percentages of CD19+ CD86+ B, CD19+ CD138+ B and CD40L+ Tfh cells significantly increased in Group C (P 0.05). No significant difference in the percentages of CD19+ B cells, CD19+ CD27+ B cells, CD19+ B cells or CD19+ CD38+ B cells expressing IgG, IgM, IgD, CD19+ B cells or CD19+ B cell subsets secreting CD40 was found between the control group and Groups A, B and C (P>0.05). Moreover, the percentages of CD19+ B and CD19+ CD38+ B cells secreting IgA and IgE in Groups A, B and C were higher than those in the control group (P<0.05). Secretion of IgA by CD19+ B and CD19+ CD38+ B cells were positively correlated with the expression of CD40L by Tfh cells (P<0.05). Conclusion Tfh cell-mediated abnormal expression of CD40/CD40L might play an important role in the development of HSP and be related to the clinical severity of renal involvement in HSPN. Key words: Henoch-Schonlein purpura; Immunoglobulin; B cell; Follicular helper T cell; CD40/CD40 ligand

The role of T cells in the development of Henoch-Schonlein purpura.

Henoch-Schonlein purpura (HSP) is an IgA-mediated disorder that most commonly occurs in children. Its etiology and pathogenesis remain unknown. In recent years, numerous studies have pointed to a dysfunction of T cells in the pathogenesis of HSP. Here, we will review the epidemiology, clinical and molecular characteristics of HSP, as well as abnormalities of Th cell subsets in this disorder. Finally, we will discuss the key factors that are involved in Th cell differentiation as potential novel targets for the prevention and treatment of HSP.

Clinical Significance of Serum Midkine in Children with Henoch-Schonlein Purpura

To investigate the clinical significance of serum midkine (MK) in children with henoch-schnlein purpura(HSP). One hundred and six children with HSP admitted in our hospital from March 2013 to March 2016 were enrolled in HSP group, but then 80 healthy volunteers were used as control. MK, interleukin-2 (IL-2), IL-4, IL-6, IL-10, tumor necrosis factor (TNF), interferon γ (IFN-γ) and IL-17 in peripheral blood were measured by ELISA, biochemical indicators including white blood cell count (WBC), platelet (Plt), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), D-dimer, immunoglobulin A (IgA), IgE, IgG, IgM and other clinical data were recorded and analyzed. Among 106 cases of henoch-schonlein purpura, 42 patients combined with renal failure (isolated hematuria in 4 cases, 17 cases of isolated proteinuria, hematuria and proteinuria in 21 cases). Midkine level in children with HSP was significantly higher than that in the control group [291.70(248.50-396.41) pg/ml vs 217.30(198.98-243.65) pg/ml)](P<0.05); the MK level in group of HSP with nephritis was higher than that in group of HSP without nephritis [326.58(266.58-459.25) pg/ml vs 280.72(233.67-384.36) pg/ml] (P<0.05). IL-4, IL-6, IL-17, TNF and IFN-γ levels in children with HSP were higher than those in the control group(P<0.05), but IL-10 level was lower than that in control group. IL-2 level was not significantly different between 2 groups. Cytokines levels in HSP nephritis group and HSP without renal involvement were not significantly different. Pearson correlation analysis showed that midkine level positively correlated with IL-4, IL-6, IL-17, IgA and IgE (P<0.05). By ROC curve analysis, the AUC of midkine was 0.902, 95% CI 0.841-0.963 (P<0.001), threshold 295.50 pg/ml. The sensitivity and specificity of midkine for predicting Henoch-Schonlein purpura nephritis were 80.60% and 88.30% respecitvely. Plasma MK plays an important role in the development of Henoch-Schonlein purpura and Henoch-Schonlein purpura nephritis. Plasma MK can be used as an effective indicator for early diagnosis and prediction of HSP and renal damage.

Circulating midkine in children with Henoch-Schönlein purpura: Clinical implications

BackgroundMidkine (MK) is a heparin-binding growth factor, which behaves like a cytokine, involved in various cellular processes such as cellular proliferation, differentiation, survival, adhesion, and migration. Studies provided evidence for a role of MK in acute and chronic inflammatory processes. The association between midkine and Henoch-Schönlein purpura (HSP) has not yet been explored. The aim of our study was to investigate the potential role of midkine in children with HSP. MethodsA total of 152 cases consisting of 92 children with HSP and 60 age- and sex-matched healthy control children were enrolled in this prospective study. Circulating midkine, IL-2, IL-4, IL-6, IL-10, TNF, IFN-γ, and IL-17A was measured in all of the 92 patients and 60 healthy controls. Midkine diagnostic value was evaluated by receiver operating characteristic (ROC) analysis. ResultsRenal involvement occurred in 36 of the 92 patients. Circulating midkine level was elevated in children with HSPN than those of patients without renal involvement and of the controls (326.58 (266.58–459.25) pg/ml versus 280.72 (233.67–384.36) pg/ml and 217.3 (198.98–243.65) pg/ml, respectively; P<0.05). Midkine positively correlated with IL-4, IL-6, IL17A, IgA and IgE. The threshold MK concentration of HSPN was 295.58pg/ml, with the sensitivity and specificity of 80.6% and 88.3%, respectively. The area under the receiver operating characteristic (ROC) curve (AUCROC) of MK was 0.902. ConclusionsMK seems to be involved in the development of HSP. Measurement of serum levels of MK is helpful in confirming the diagnosis of HSP and predicting HSPN.

Current views of the relationship between Helicobacter pylori and Henoch-Schonlein purpura in children.

Helicobacter pylori (H. pylori) is one of the factors involved in the pathogenesis of various gastrointestinal diseases and may play a potential role in certain extra-intestinal diseases. H. pylori infection are mainly acquired during childhood, and it has been reported that in endemic areas of China the infection rates are extraordinarily higher in HSP children, particular those with abdominal manifestations. Furthermore, eradication therapy may ameliorate Henoch-Schonlein purpura (HSP) manifestations and decrease the recurrence of HSP. Therefore, results suggested that detection of H. pylori infection by appropriate method ought to be applied in HSP children. Current evidences indicate that local injury of gastric mucosa and immunological events induced by H. pylori infection are involved in the development of HSP. Increased serum IgA, cryoglobulins, C3 levels, autoimmunity, proinflammatory substances and molecular mimicry inducing immune complex and cross-reactive antibodies caused by H. pylori infection might play their roles in the course of HSP. However, there are no investigations confirming the causality between H. pylori infection and HSP, and the pathogenesis mechanism is still unclear. More bench and clinical studies need to be executed to elaborate the complex association between H. pylori and HSP.

Chemokine MCP1/CCL2 gene polymorphism influences Henoch-Schönlein purpura susceptibility in Iranian Azeri-Turkish patients.

Henoch-Schönlein purpura (HSP) is the most common small-vessel vasculitis and mainly affects children. Although its pathophysiology is unknown, several studies have indicated the possible involvement of infections and genetic factors in the development of HSP. The human leukocyte antigen (HLA) gene family and several other genes involved in the inflammatory system have been studied. The CCL2 gene, encoding chemokine monocyte chemo-attractant protein 1 (MCP-1/CCL2), is one of several cytokine genes clustered on chromosome 17. The encoded protein displays chemotactic activity for monocytes. This is a case-control study comparing 36 children diagnosed with HSP within the Iranian Azeri-Turkish ethnic population and 50 healthy adults from the same ethnic group. CCL2, C-2518T polymorphism genotypes were determined by polymerase chain reaction and by PVUII restriction enzyme analysis and subsequent agarose gel electrophoresis. Our results showed a significant association between the allelic and genotypic frequency of this gene and HSP disease in this cohort. The results of this study indicate that frequencies of the T allele of CCL2 (P=0.015) and the TT genotype (P=0.004) are significantly higher in HSP patients. A comparison of clinical symptoms and laboratory data with CCL2 C-2518T polymorphism showed that patients with the TT genotype presented a higher clinical score and more severe clinical features. MCP1/CCL2 C-2518T gene polymorphism is associated with susceptibility to HSP. This is the first study to report a significant association between MCP1/CCL2 C-2518T and a susceptibility to HSP in this population.

Increased serum levels of soluble vascular endothelial-cadherin in patients with systemic vasculitis

Henoch-Schönlein purpura (HSP) is a commonest systemic vasculitis (SV) in childhood characterized by an inflammatory reaction directed at vessels. Endothelial damage and perivascular leukocyte infiltrates are vital in the development of HSP. Vascular endothelial (VE)-cadherin is an endothelial cell-specific adhesion molecule, which plays critical roles in angiogenesis and endothelial integrity. Herein, we investigated the serum levels of soluble VE-cadherin (sVE-cadherin) in patients with HSP and other forms of SV. The serum levels of sVE-cadherin in 30 patients with HSP, together with patients with urticarial vasculitis, allergic vasculitis, Behcet disease, psoriasis vulgaris (PV) and atopic dermatitis (AD) and 26 health controls were measured by enzyme-linked immunosorbent assay. Serum levels of sVE-cadherin were significantly increased in patients with HSP in acute stage and patients with other forms of SV but not in patients with PV or AD. Moreover, Serum sVE-cadherin levels in HSP patients were correlated with the severity of this disease and serum concentrations of IgA anticardiolipin antibodies and vascular endothelial growth factor. Taken together, we show firstly that serum sVE-cadherin is abnormally increased in HSP patients. Increased serum levels of sVE-cadherin might be a novel biomarker for evaluating the severity of HSP and useful for identifying the presence of SV in inflammatory skin conditions.

Elevated serum interleukin-33 levels in patients with Henoch-Schönlein purpura

Henoch-Schönlein purpura (HSP) is the most common systemic vasculitis and is known as an immunoglobulin (Ig) A related immune complex-mediated disease. However, the molecular mechanisms in the development of HSP are not yet fully understood. Herein, we investigated the serum levels of Interleukin (IL)-33 and soluble ST2 (sST2) in HSP patients and their association with disease severity and IgA autoantibodies production. The serum levels of IL-33 and sST2 were measured by double antibody sandwich enzyme-linked immunosorbent assay (ELISA) in the serum of 33 patients with HSP and 22 controls. Serum levels of IgA anti-endothelial cell antibodies (AECA) and IgA anticardiolipin antibodies (ACA) in HSP patients were detected by double antigen sandwich ELISA. Our results indicated that serum levels of IL-33 but not sST2 were significantly elevated in patients with HSP in acute stage and restored to normal levels in convalescent stage. Moreover, serum IL-33 levels were correlated with the severity of HSP and serum concentrations of AECA-IgA and ACA-IgA. Taken together, we show firstly that serum IL-33 is abnormally elevated in HSP patients. IL-33 might be associated with the IgA autoantibodies production in the pathogenesis of HSP.

Methylenetetrahydrofolate reductase C677T polymorphism in patients with Henoch‐Schönlein purpura

Associations between several vascular diseases such as Kawasaki disease, venous and arterial thromboembolism, cardiovascular disease, diabetic nephropathy, focal segmental glomerulosclerosis and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism have been reported. This is a clinical study designed to investigate the possible effects of MTHFR C677T polymorphism on the development of Henoch-Schönlein purpura (HSP). Forty-one patients with HSP (25 male/16 female) with a mean age of 7.8 ± 2.9 years were included in the study. The control group consisted of 50 healthy children. MTHFR genotypes were determined by polymerase chain reaction and by Hindf I restriction enzyme analysis and subsequent 3% agarose gel electrophoresis techniques. No significant differences were observed in the distribution of MTHFR genotypes or allele frequencies in the HSP cases versus controls. Plasma homocysteine levels and vitamin B(12) levels were almost comparable in the HSP patients and control group without a significant difference. Folic acid levels were within normal limits in the HSP cases and the control group, HSP patients' levels being significantly higher than the control group. No significant relationship was present with the MTHFR genotype and plasma homocysteine, vitamin B(12) and folic acid levels in HSP patients. No association with MTHFR gene polymorphism and homocysteine plasma levels could be found in patients with HSP. The results of this study indicate that other mechanisms should be operative in the development of HSP.

The Pathogenesis of Henoch-Schönlein Purpura by Malaria

Sir, We read with great interest the recent contribution by Thapa et al. They reported a 9-year-old boy with Henoch–Schonlein purpura (HSP) triggered by falciparum cerebral malaria and speculated that HSP may be associated with increased IgA levels and reduced factor XIII levels. However, we would like to add some possible mechanisms to the development of HSP by cerebral malarial infection. Davin et al suggested that a significant increase in IgA plasma levels might be related to an impairment of the reticuloendothelial system (RES) function during the acute phase of HSP. Similarly, Mibei et al reported that a reduction of the clearance of immunoglobulins by downregulation of Fc receptors might explain the association of both increased immunoglobulin levels and circulating immune complexes with cerebral malaria. Troye-Blomberg et al also showed that elevated levels of serum antibodies to activating malaria antigens are associated with the production of interleukin-4 (IL-4) by activated human T cells, which can upregulate Fc receptors for IgE (FceRII) on macrophages that could lead to the release of tumor necrosis factor (TNF)-a, a potent proinflammatory cytokine elevated in children with cerebral malaria. Because TNF-a is regarded as one of the contributing factors to the development of HSP, and Kawasaki et al described that serum IL-4 concentrations were significantly elevated at the acute phase in HSP patients, there is a possibility that the dominance of Th-2 cytokines in malarial infection might affect the development of HSP, which is often associated with elevated IgE. Therefore, we speculate that not only increased IgA levels due to reduced Fc-receptor function in RES system but also elevated IL-4, TNF-a, and IgE levels might contribute to the development of HSP triggered by falciparum cerebral malaria. However, further studies are necessary to elucidate whether decreased factor XIII levels themselves during malarial infection could contribute to the development of HSP, because they are often considered to be a secondary process by inflammatory reaction due to vasculitis rather than a primary process.

Púrpura de Schönlein-Henoch. Estudio de factores asociados con el desarrollo y evolución de la enfermedad

Henoch-Schönlein purpura (HSP) is the most common form of pediatric vasculitis. The objective of this study was to determine the factors associated with the development and course of this disease. A case-control study was performed. The case group included patients with HSP followed-up at the pediatric rheumatology and nephrology units of a tertiary university hospital over a 2-year period. The control group included children followed-up at the pediatric rheumatology unit for mechanical or non-inflammatory conditions. A medical history including data on infectious conditions and previous medication was taken. A throat culture was performed and antistreptolysin 0 levels were quantified. The seroprevalence of different viruses was investigated. Subsequently, the patients were prospectively followed-up and disease manifestations were compared with reported epidemiological factors. Seventy patients and 58 controls were studied. A history of a recent upper respiratory infection (URI) and antibiotic intake were independently associated with development of HSP. Palpable purpura was present in 100 % of the patients. Gastrointestinal manifestations were recorded in 63 %, articular in 50 %, and renal in 18.6 %. Arthralgias were more frequent in girls and purpura duration was longer when disease onset occurred in spring or summer. Other factors studied were not associated with disease development or with a worse clinical course. Factors associated with the development of HSP were a history of URI and antibiotic administration. Other epidemiological factors studied were not associated with either the development or the course of the disease.

Henoch–Schonlein purpura

Summary This review summarises the evidence from the latest published research on the epidemiology, aetiology, pathophysiology, clinical manifestations, treatment, and prognosis of Henoch–Schonlein purpura (HSP). Analysis of the literature indicates the importance of genetic and infectious aetiologic considerations in the development of HSP. And, within the last year, multiple inflammatory markers have been studied in association with the disease. Although, the common complaints associated with HSP are well known, the disease can also be associated with sequalae in multiple organ systems, as well as vasculitis throughout the body. No consensus has yet been agreed upon regarding treatment methodology of disease complications, but prognostic studies have determined that 6 months is appropriate in which to follow-up children to monitor for renal complications. Recent literature indicates the continued interest in defining the aetiology, complete clinical manifestations, treatment options and prognostic markers of HSP and the complications from the disease.

Henoch-Schonlein purpura.

The purpose of this review is to educate the reader about the one of the most common vasculitides of childhood: Henoch-Schonlein purpura. Although the disease has been described for over a century, the etiology has yet to be discovered. Adult-onset Henoch-Schonlein purpura is unusual, but through case studies, this review examines some of the common manifestations of this presentation of disease. Long-term outcome studies are still defining how this disease affects a small but significant percentage of patients afflicted with Henoch-Schonlein purpura. This article will summarize recent work in molecular biology and genetics evaluating predisposing factors in the development of Henoch-Schonlein purpura. Further illustrations of the various complications of Henoch-Schonlein purpura will be reviewed. Recent long-term studies of outcomes of patients with renal disease from Henoch-Schonlein purpura will be summarized. After reading this review, the clinician will be able to elucidate the manifestations of Henoch-Schonlein purpura, determine appropriate treatment of the disease, and, most importantly, give the patient information about long-term consequences of Henoch-Schonlein purpura.

IgA myeloma presenting as Henoch-Schönlein purpura with nephritis

IgA nephropathy (IgAN) and Henoch-Schönlein purpura (HSP) are both characterized by IgA-mediated tissue injury, including mesangial proliferative glomerulonephritis. Abnormalities of IgA1 glycosylation are described in IgA nephropathy and HSP nephritis. IgA-antineutrophil cytoplasmic antibodies (ANCA) have been inconsistently described in the serum of patients with HSP. In IgA myeloma, the paraprotein-mediated renal lesion is typically cast nephropathy; IgAN or HSP have only rarely been reported in myeloma even when an IgA paraprotein is circulating in large concentrations. We report the case of a 50-year-old man with IgA myeloma who presented with HSP including nephritis and rapidly progressive renal failure. His IgA1 had altered O-glycosylation in the pattern seen in IgAN and also contained an IgA-ANCA. This case adds further weight to the evidence that IgA1 O-glycosylation abnormalities predispose to mesangial IgA deposition and also that IgA-ANCA may have a pathogenic role in the development of HSP.