Pathogenesis Of Henoch-Schonlein Purpura Research Articles

Proanthocyanidins: A novel approach to Henoch‑Schonlein purpura through balancing immunity and arresting oxidative stress via TLR4/MyD88/NF‑κB signaling pathway (Review).

Henoch-Schonlein purpura (HSP), a recurrent and immunoglobulin (Ig)A-mediated vasculitis, presents not only as skin lesions but also as systemic involvement that can be life-threatening. Although the etiology of HSP remains unknown, immune imbalance and oxidative stress (OS) are primary contributors to its pathogenesis, alongside the abnormal activation of Toll-like receptor (TLR)/myeloid differentiation primary response gene 88 (MyD88)/nuclear factor-κB (NF-κB) pathway. TLRs, especially TLR4, stimulate downstream signaling molecules such as NF-κB and proinflammatory cytokines, which are released when TLRs combine with the key adapter molecule MyD88. This leads to the activation of T helper (Th) cell 2/Th17 and overproduction of reactive oxygen species (ROS). The function of regulatory T (Treg) cells is suppressed in the process. Th17/Treg imbalance then produces various inflammatory cytokines to promote proliferation and differentiation of B cells and the secretion of antibodies. IgA is secreted, and it binds to vascular endothelial surface receptors where the complex induces injury of the vascular endothelial cells. Additionally, excessive ROS creates OS that leads to an inflammatory response and vascular cell apoptosis or necrosis, thereby contributing to vascular endothelial damage and HSP occurrence. Proanthocyanidins are active compounds naturally enriched in fruits, vegetables and plants. Proanthocyanidins have diverse properties, including anti-inflammatory, antioxidant, antibacterial, immunoregulatory, anticarcinogenic and vascular protective effects. Proanthocyanidins are used in the management of various diseases. Proanthocyanidins regulate T cells, equilibrate immunity and arrest OS by inhibiting the TLR4/MyD88/NF-κB signaling pathway. Considering the pathogenesis of HSP and the properties of proanthocyanidins, the present study hypothesized that these compounds may potentially lead to HSP recovery through modulating the immune equilibrium and preventing OS by inhibiting the TLR4/MyD88/NF-κB pathway. To the best of our knowledge, however, little is known about the positive effects of proanthocyanidins against HSP. The present review summarizes the potential of proanthocyanidins to treat HSP.

Henoch-Schonlein Purpura in Adult with Gastrointestinal and Renal Involvement

Background: The pathogenesis of Henoch-Schonlein Purpura (HSP), a multisystem organ-involved small vessel vasculitis, is unknown. HSP is more common in youngsters than in adults. HSP is associated with a history of malignancies, medications, vaccinations, and upper respiratory tract infections. Painful purpura, arthritis, stomach discomfort, and renal involvement are symptoms that may be seen in HSP patients. Adult patients had a much higher rate of renal involvement than children. Purpose: To report a case of HSP in an adult with gastrointestinal and renal involvement. Case: A 45-year-old man complained of an arm, leg, and waist rash for two weeks before admission to the hospital. He also has stomach pains, nausea, and vomiting to deal with. His symptoms have just appeared now for the first time. During a renal function test, blood urea nitrogen (BUN) and creatine serum levels rose. On a urinalysis, proteinuria and microscopic hematuria were found. Leucocytoclastic vasculitis was discovered during the histopathology investigation. HSP diagnosis was based on the ACR and ICC criteria. The patient was given 3x2 tablets of 0.5 mg dexamethasone, 3x2 tablets of cetirizine, 2x10 mg lisinopril, 2x50 mg ranitidine injection, and 2 grams ceftriaxone. Discussion: The clinical symptoms of HSP are used to make the diagnosis. In the vast majority of instances, the treatment is only supportive therapy. Corticosteroid usually are usually used for HSP with multisystem organ involvement to reduce pain severity and faster resolution of renal manifestation. Conclusion: Follow up on renal function is needed to monitor the worsening of renal disease.

Increased circulating innate lymphoid cell (ILC)1 and decreased circulating ILC3 are involved in the pathogenesis of Henoch-Schonlein purpura

BackgroundInnate lymphoid cell (ILC) dysfunction is involved in numerous immune diseases, but this has not been demonstrated in Henoch-Schonlein purpura (HSP). This study aimed to investigate whether ILC dysfunction or imbalance participate in the pathogenesis of HSP.MethodsThis was a prospective study in patients with HSP who were hospitalized at the Children’s Hospital of Soochow University from June to December 2019. Age- and sex-matched controls were also enrolled. ILC subsets and lymphocyte subpopulations were determined by flow cytometry. The transmission immune turbidimetric method also facilitated the exploration of correlations between ILC subset frequency and lymphocyte subpopulation, as well as serum IgA in HSP patients.ResultsFifty-one patients with HSP and 22 control patients were included. There were no differences in age and sex between the two groups. Compared with controls, patients with HSP had higher ILCs in relation to lymphocytes (P = 0.036), higher ILCs in relation to PBMCs (P = 0.026), higher ILC1s (P < 0.001), lower ILC3s (P < 0.05), and higher ILC1/ILC3 ratio (P < 0.001). Sixteen patients underwent routine therapy combined with methylprednisolone for 7–10 days; ILC1s were significantly decreased (P < 0.001) and ILC3s were increased (P = 0.033), and ILC1/ILC3 was significantly decreased (P < 0.001). Compared with the controls, the ratios of ILCs/lymphocytes and ILCs/PBMC were higher in patients in the arthritis and mixed groups (all P < 0.05). ILC1 were elevated in the purpura, arthritis, abdominal, and mixed groups (P = 0.027, P = 0.007, P < 0.001, and P < 0.001, respectively). ILC1/ILCs were positively correlated with CD3 + CD8 + T lymphocytes (r = 0.3701, P = 0.0075). The level of IgA did not correlate with ILCs.ConclusionsHigher circulating ILC1s and lower circulating ILC3s appear to be involved in the pathogenesis 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.

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.

Characteristics of immune function in the acute phase of Henoch-Schönlein purpura.

Henoch-Schönlein purpura (HSP) is still diagnosed using symptoms and signs together with some histopathological findings. The purpose of this study was to summarize the characteristics and roles of cellular and humoral immunity in children with Henoch-Schönlein purpura (HSP). A total of 502 cases of patients with acute HSP were diagnosed and observed. The levels of T lymphocyte subsets, natural killer cells (NK cells), and B cells were analyzed by flow cytometry. The serum immunoglobulin G (IgG), immunoglobulin M (IgM), immunoglobulin A (IgA), and complement C3 (C3) and complement C4 (C4) levels were detected by velocity scatter turbidimetry. Compared with the healthy groups, the levels of cluster of differentiation 3 (CD3), cluster of differentiation 4 (CD4), B cells, and NK cells and ratio of CD4/CD8 in patients with HSP were decreased (P < 0.05). The levels of IgG, IgA, IgM, and C3 were increased (P < 0.05). Compared with the Kawasaki disease (KD) group, the levels of CD3, CD4, CD8, B cells, NK cells, and IgA in patients with HSP were increased (P < 0.05), and the ratio of CD4/CD8 and levels of IgM, C3, and C4 was decreased (P < 0.05). Compared with the pneumonia group, the levels of CD3, CD4, B cells, and IgA in patients with HSP were increased (P < 0.05), and the ratio of CD4/CD8 and levels of IgM and C4 was decreased (P < 0.05). Cellular immunity and humoral immunity were all involved in the pathogenesis of HSP. The decline of NK cells, B lymphocyte cells, CD3, CD4 the increased secretion of immunoglobulin, and the abnormal appearance of IgA and C3 may exist during the progression. It may indicate a worse prognosis and increasing the risk of dedifferentiation. Cellular immunity was lower, which lead to increased production of inflammatory mediators and increased secretion of immunoglobulin, which then mediated systemic small-vessel vasculitis. Key Points • The pathogenesis of Henoch-Schönlein purpura (HSP) was not completely illuminated. • There was a lack of disease-specific laboratory abnormalities that can be used in the clinical diagnosis of HSP. • We compared the laboratory abnormalities in the immune system of HSP with KD and pneumonia. • Cellular immunity and humoral immunity were all involved in the pathogenesis of HSP. Cellular immunity was lower, which lead to the following pathological changes.

The Anti-inflammatory Effects of HMGB1 Blockades in a Mouse Model of Cutaneous Vasculitis.

In our previous study, we have found increased serum levels of HMGB1 in patients with Henoch– Schonlein purpura (HSP), allergic vasculitis (AV), and urticarial vasculitis (UV) and altered HMGB1 distribution in lesional skin in patients with HSP. HMGB1 plays a pro-inflammatory role in the pathogenesis of HSP. To further investigate the role of HMGB1 in the pathogenic mechanism of vasculitis, we investigated the anti-inflammatory effects of HMGB1 blockades (including anti-HMGB1 mAb and glycyrrhizin) in a mouse model of a cutaneous reverse passive Arthus (RPA) reaction. A total of 36 balb/c mice were randomly divided into four groups: the control group, IC model group, HMGB1 monoclonal antibody (anti-HMGB1-mAb) group and the glycyrrhizin group, with nine mice in each group. A cutaneous RPA reaction mouse model was established by injections of the OVA antibody and the OVA antigen. Mice of the anti-HMGB1-mAb group and glycyrrhizin group were pre-treated with anti-HMGB1 mAb or glycyrrhizin, respectively, before the RPA reaction. Our results indicated that HMGB1 blockades (anti-HMGB1 mAb and glycyrrhizin) obviously extenuated the severity of vasculitis skin damage and improved the histological evolvement of inflammatory cells infiltration, vascular fibroid necrosis, and vasodilation in a cutaneous RPA reaction mouse model. In addition, HMGB1 blockades reduced the infiltration of neutrophils, DCs, and T cells and decreased the mRNA expression of IL-6 and CCL5 in skin lesions in the cutaneous RPA reaction mouse model. We suggest that HMGB1 blockades may represent a new direction for the treatment of cutaneous vasculitis.

Exploration of susceptible genes associated with Henoch–Schönlein purpura by whole exome sequencing

Henoch-Schönlein purpura (HSP) is a systemic small-vessel vasculitis caused by environmental and inherent factors. Although recent research has advanced our understanding of the role of genetic susceptibility in HSP, there are still significant gaps in our knowledge. In this study, we aimed to explore some susceptibility genes likely associated with HSP. Three DNA samples from a family with HSP were used to perform whole exome sequencing with Illumina Hiseq 2500 high-throughput sequencing. The relevant single nucleotide variants (SNVs) were screened according to specific filter conditions and the screened SNVs were then verified with Sanger sequencing. The Sanger sequencing results were further screened according to available literature. Finally, candidate genes were validated in 92 samples from children with HSP, and also in 1 child with HSP from HSP family, using the polymerase chain reaction technique (PCR). Our analysis revealed that the MIF gene and the MGAT5 gene related to immunity remained after screening. Among the 93 children with HSP, there were 3 patients with MIF mutations and 2 patients with MGAT5 mutations. Our findings are helpful for providing new methods and ideas for understanding the pathogenesis of HSP by detecting and analyzing gene mutations at the whole-exome level including multi-generation sequencing. MIF and MGAT5 may be new susceptibility loci for HSP, but their roles in the pathogenesis of HSP are worthy of further study.

Serum level of advanced oxidation protein products (AOPPs) in patients with Henoch-Schonlein purpura and its relationship with aberrant glycosylation of IgA1 and Cosmc mRNA expression.

BackgroundHenoch–Schonlein purpura (HSP) is a systemic small vessel vasculitis that is mainly caused by IgA1‐type immune complex deposition. Advanced oxidation protein products (AOPPs) are specific markers of protein oxidation.ObjectiveTo explore the role of AOPPs in the pathogenesis of HSP.MethodsThere are 51 HSP patients who were divided into four subgroups: (i) skin type – 20 cases; (ii) joint type – 8 cases; (iii) abdominal type – 12 cases; (iv) renal type – 11 cases; and 18 healthy volunteers were enrolled as controls. The serum levels of AOPPs and Gd‐IgA1 were quantified by an HAA‐lectin‐based ELISA. The Cosmc mRNA expression in peripheral B lymphocytes was measured by RT‐PCR.Results1. Advanced oxidation protein products in different subgroups of HSP patients are all higher than the controls, while the renal‐type subgroup is the highest and the skin‐type subgroup is the lowest. 2. Spearman correlation analysis shows that: (i) AOPPs and Gd‐IgA1 in HSP patients are positively correlated; both of them are positively correlated with the disease severity scores; (ii) AOPPs are negatively correlated with the relative expression value (RQ) of Cosmc mRNA.ConclusionAdvanced oxidation protein products play an important role in the pathogenesis of HSP, especially in renal‐type patients.

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.

Expression and significance of endothelial microparticles in children with Henoch-Schönlein purpura

To study the expression and significance of endothelial microparticles (EMPs) in children with Henoch-Schönlein purpura (HSP). A total of 100 previously untreated children with HSP were classified to Henoch-Schönlein purpura nephritis (HSPN) group (n=40) and non-nephritis group (n=60). Thirty healthy children who underwent physical examination were enrolled as control group. Serum levels of EMPs, T helper 17 cells (Th17), and interleukin-17 (IL-17) were compared between groups. The HSPN and non-nephritis groups had significantly higher levels of Th17 and IL-17 than the control group, and the HSPN group had the highest levels (P<0.05). The HSPN and non-nephritis groups had a significantly higher level of EMPs than the control group, and the HSPN group had the highest level (P<0.05). In the HSPN group, the levels of Th17 and IL-17 were positively correlated with the level of EMPs (r=0.830 and 0.644 respectively; P<0.05). EMPs play an important role in the pathogenesis of HSP. The increase in EMPs might be one of the reasons for renal involvement in children with HSP.

Role of Th17 Cells, Interleukin-17 and Matrix Metalloproteinase-13 in Pathogenesis of Henoch-Schonlein Purpura

To explore the immunopathogenesis of Henoch-Schonlein purpara (HSP) by detecting the levels of Th17 cells, IL-17 and matrix metallo proteinase-13 (MMP-13) in peripheral blood and the expression of IL-17 in skin lesions at acate phase of HSP. Th17 cell ratio in peripheral blood of HSP group and healthy control group was defected by flow cytometry, the plasma levels of IL-17 and MMP-13 in HSP group and healthy control group were defected by ELISA, and expression level of IL-17 in skin lesion of HSP group and skin tissue of healthy control group was deternined by: immunohistochemistry method. the ratio of Th17 cells in periphral blood of HSP group (1.21±0.59%) was very signif cantly higher than that in peripheral blood of control group (0.71±0.26%) ( t=4.907, P<0.01). The plasma levels of IL-17 and MMP-13 at acute phase of HSP were very significantly higher than those in control group (64.58±36.21) pg/ml vs (26.16±14.90) pg/ml and (17.57±5.40) pg/ml vs (11.53±4.40) pg/ml respectively (t=6.183, P<0.01 and t=5.022, P<0.01). The integrool optical density of IL-17 in skin lesin tissue of HSP group (7.26±2.34) was higher than that in control group (4.61±1.82) ( t=2.877, P<0.01). Th17 cells, IL-17 and MMP-13 may be involved in the immunological pathogenesis of HSP.

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.

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.

Association of Endothelial Nitric Oxide Synthase Gene Polymorphism with Susceptibility and Nephritis Development of Henoch-Schönlein Purpura in Chinese Han Children.

Henoch-Schönlein purpura (HSP) is the most common form of systemic small-vessel vasculitis in children. Previous studies suggested endothelial nitric oxide synthase (eNOS) plays an important role in the pathogenesis and clinical manifestations of HSP. This study aimed to investigate the potential association between 10 single-nucleotide polymorphisms (SNPs) within the eNOS gene and HSP risk and nephritis development in a Chinese Han population. A case-control study was conducted including 459 healthy children and 423 children with HSP. SNPs were genotyped by using the MassARRAY system. The genotypic frequency of rs11771443 was nominally associated with the risk of HSP (p = 0.010), and the C allele significantly increased the risk of HSP (p = 0.003, odds ratio [OR] = 1.331, confidence interval [95% CI] = 1.104-1.605). There was a significant difference in allelic and genotypic distribution of rs1799983 between children with HSP and healthy controls (p = 0.002 and 0.0001, respectively). Strong linkage disequilibrium was observed in two blocks. Significantly fewer T-A-G haplotypes (p = 0.0001, OR = 0.593, 95% CI = 0.448-0.786) were found in children with HSP. No significant association was identified between the 10 SNPs and the pathogenesis of HSP progression to HSP nephritis (HSPN). The polymorphisms of eNOS contribute to genetic susceptibility to HSP, but may have no effect on children with HSP progressing to HSPN.

Histopathological and immunological changes during the acute and recovery phase in Henoch-Schönlein purpura rabbit model.

Henoch-Schönlein purpura (HSP) is a systemic vasculitis mediated by autologous immune complex. Animal models of HSP are scarce. Here, we describe the characteristics of HSP rabbit model in the acute and recovery phase. First, we constructed the HSP rabbit models, and then assessed immunologic indicators of models by enzyme-linked immunosorbent assay and immunoturbidimetry. Histomorphological characteristics were analyzed by haematoxylin-eosin, immunofluorescence and special staining. In the acute stage (24h) after antigen challenge, the model group rabbits featured skin ecchymosis and abnormal laboratory examination results. Three weeks following the allergic reaction, purple spots improved markedly, and edema and blood seeping decreased, but obvious inflammation was present in the skin, kidneys, joints, gastrointestinal, lung and liver. Serological results of CD4, CD/CD8, IL-2, IL-4, and TNF-α, IgA, IgG, TropI, Alb and T were still abnormal. IgA and C3 expressed in skin and kidney and eosinophils expressed in skin and lungs were increased. The rabbit model can mimic human HSP lesions in symptoms, pathology, and immunology and may provide valuable insight into the pathogenesis of HSP and serve as a tool for future therapeutic development targeting HSP.

Parainfluenza infection is associated with Henoch-Schönlein purpura in children

Abstract Background To investigate the association of respiratory tract viruses with Henoch-Schonlein purpura (HSP) in children. Methods 40 children with HSP and 42 controls with upper respiratory tract infections were enrolled in the study. In both groups, the serum IgM antibodies and viral antigens in peripheral blood mononuclear cells (PBMCs) of common respiratory tract viruses including parainfluenza virus (PIV), influenza, respiratory syncytial virus (RSV), and adenovirus were detected. Children with HSP nephritis (HSPN) received renal biopsy, and antigens of the aforementioned viruses were examined. Results Viral IgM antibodies in sera and antigens in PBMCs were detected in HSP and control groups (55% vs. 42.9% and 60% vs. 42.9% respectively), but the differences were not significant. The prevalence of PIV IgM antibody and antigen in PBMCs in HSP group was significantly higher than that in controls (P Conclusions The presence of respiratory tract viruses was common in HSP children. PIV may be an important contributing factor in the pathogenesis of HSP.

Atopic Dermatitis and Association of Risk for Henoch-Schönlein Purpura (IgA Vasculitis) and Renal Involvement Among Children: Results From a Population-Based Cohort Study in Taiwan.

Elevation of Th2 cytokine-driven inflammatory mediators has been reported in acute stage of Henoch–Schönlein purpura (HSP). However, the temporal interaction between Th2-mediated allergic diseases and HSP with renal involvement remains unknown. Herein, we conducted a population-based cohort analysis to investigate the risk of HSP and renal involvement in children with atopic dermatitis (AD) as 1 of the first steps in the atopic march.From 2000 to 2007, 95,208 children with newly diagnosed AD and 190,416 randomly selected non-AD controls were included in the study. By the end of 2008, incidences of HSP in both cohorts and the AD cohort to non-AD cohort hazard ratios (HRs) and confidence intervals (CIs) were measured. Comparison of renal involvement in HSP between children with and without AD was analyzed.The incidence of HSP during the study period was 1.75-fold greater (95% CI: 1.27–2.42) in the AD cohort than in the non-AD cohort (14.2 vs 8.11 per 100,000 person-years). The AD to non-AD HR of HSP was greater for girls (1.92, 95% CI: 1.18–3.13), children older than 6 years (2.54, 95% CI: 1.15–5.59), and those living in less urbanized area (2.74, 95% CI: 1.10–6.82). Concurrent allergic rhinitis or asthma did not increase the HR of HSP further. The HR for HSP in AD children increased from 0.67 (95% CI: 0.41–1.11) for those with ≤2 AD-related visits to 9.77 (95% CI: 6.44–14.8) for those with >4 visits (P < 0.0001, by the trend test). The risk of developing HSP in the AD cohort was highest within first year after AD diagnosis (HR: 3.99; 95% CI: 1.61–9.89). AD cohort with HSP had higher occurrence rate of renal involvement, particular hematuria, than non-AD cohort with HSP.AD children had a greater risk of developing HSP and HSP with renal involvement. Further research is needed to clarify the role of allergy in the pathogenesis of HSP and renal involvement.

Progress in immunopathogenesis of Henoch-Schonlein purpura

Henoch-Schonlein purpura is a common general small-vessel vasculitis among children. The purpura repeated easily. It′s called Henoch-Schonlein purpura nephritis when kidney is involved. The pathogenesis of Henoch-Schonlein purpura is unknown. In many researches, the levels of serum cytokines are abnormal expression, such as IL-6, IL-21, and IL-33. In rencent researches, cytokines′ abnormal expression plays a fatal role in pathogenesis of Henoch-Schonlein purpura and Henoch-Schonlein purpura nephritis. Key words: Henoch-Schonlein purpura; Cytokine

Expansion of Circulating T Follicular Helper Cells in Children with Acute Henoch-Schönlein Purpura.

Henoch-Schönlein purpura (HSP) is a common systemic small vessel vasculitis in children with disorder autoimmune responses. T follicular helper (TFH) cells play crucial roles in regulating immune responses. The aim of our study was to investigate the probable role of TFH cells in the pathogenesis of children with HSP. In this study, the frequency of circulating CXCR5+CD4+TFH cells with inducible costimulator (ICOS) expression in the children with acute HSP was significantly higher than that in healthy controls (HCs) but not CXCR5+CD4+TFH cells with programmed death-1 (PD-1) expression. Moreover, serum levels of IL-21 and IL-6 cytokines, IgA, and C3 in HSP children were also significantly higher than those in HCs. A positive correlation was observed between the frequencies of circulating ICOS+CXCR5+CD4+TFH cells and the serum IL-21 or IgA levels of acute HSP children, respectively. Additionally, the mRNA expression levels of interleukin- (IL-) 21, IL-6, and transcriptional factors (B-cell lymphoma-6, Bcl-6) were also significantly increased in peripheral blood from acute HSP children compared to HCs. Taken together, these findings suggest that TFH cells and associated molecules might play critical roles in the pathogenesis of HSP, which are possible therapeutic targets in HSP children.