Pathogenesis Of Henoch-Schonlein Purpura Research Articles

RESEARCH OF MANNOSE-BINDING LECTIN AND INTERLEUKINS 10, 12, AND 18 IN CHILDREN WITH HENOCH-SCHÖNLEIN PURPURA

INTRODUCTION: Henoch-Schönlein Purpura (HSP) is a common vasculitis in children, and the unbalance of T-helper 1/T-helper 2 plays an important part in its pathogenesis. Mannose-binding lectin (MBL) is an important component of innate immunity and related with a lot of diseases with immunologic derangement. However, we do not know the relationship between MBL and HSP. OBJECTIVE: We aimed to explore the serum level and gene polymorphisms of MBL and the levels of interleukin 10 (IL-10), IL-12, and IL-18 in supernatant of peripheral blood mononuclear cells of children with HSP and HSP nephritis (HSPN) and of healthy children. METHODS: The concentrations of MBL and IL-10, IL-12, and IL-18 were measured by enzyme-linked immunosorbent assay: MBL gene polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism and polymerase chain reaction with sequence-specific primers. RESULTS: The serum MBL levels in the 23 children with HSP were not significantly different from 27 children with HSPN (P = .95) or 18 normal children. The levels of IL-18 in the supernatant of peripheral blood mononuclear cells in the 3 groups were not significantly different from each other (P = .47, .15, and .14). The levels of IL-10 in children with HSP and HSPN were not different from each other (P = .70), but both were significantly different from those in the normal children (P = .04 and .01). The levels of IL-12 in children with HSP were different from those in the children with HSPN (P = .04). The MBL promoter genotype and the frequency of alleles were not different between the children with HSP and HSPN or between those 2 groups compared with the normal group. CONCLUSIONS: IL-12 probably plays an important role in the renal involvement in HSP. The position of MBL in the pathogenesis of HSP and HSPN remains to be confirmed.

Neutrophil activation, protein oxidation and ceruloplasmin levels in children with Henoch-Schönlein purpura

The aim of this study was to investigate the role of neutrophil activation, protein oxidation and ceruloplasmin (CLP) in the pathogenesis of Henoch-Schönlein purpura (HSP), which has not been investigated previously. Serum activities of myeloperoxidase (MPO) and arylesterase (ARYL) and levels of free thiol groups, CLP and total oxidant status (TOS) were measured in 29 children with HSP at the onset of the disease and during remission in comparison with 30 healthy subjects. Patients at active stage had significantly higher MPO activity (391+/-277 vs. 155+/-154 U/l, P<0.001), higher CLP (832+/-120 vs. 682+/-114 mg/dl, P<0.001) and TOS values (20.7+/-11.8 vs. 7.5+/-2.8 micromol H2O2/l, P<0.001) than the controls, respectively. Patients had significantly lower ARYL activity (158x10(3)+/-39x10(3) vs. 187x10(3)+/-46x10(3) U/l, P<0.001) and lower free thiol levels (234+/-48 vs. 279+/-26 micromol/l, P<0.001) than the controls, respectively. Significantly positive correlations were found between TOS and MPO (r=0.437, P=0.018) and TOS and CLP (r=0.409, P=0.028) at disease onset, whereas a negative correlation was found between MPO and thiol (r=-0.597, P=0.001) during remission. In conclusion, protein oxidation and neutrophil activation may play important roles in the pathogenesis of HSP. Further research is required to understand the potential linkage between oxidant stress and complications and to develop therapeutic strategies in HSP.

Lack of association between NPHS2 gene polymorphisms and Henoch-Schönlein purpura nephritis

Henoch-Schönlein purpura (HSP) is one of the most common forms of small-vessel vasculitis in childhood, and renal involvement (HSP nephritis, HSPN) is the main determinant of morbidity after acute phase. Considering the racial diversity and clinical heterogeneity in the prevalence, genetic factors might play a role in pathogenesis of HSP and HSPN. Direct sequencing was performed after PCR amplification of all 8 exons of the NPHS2 gene in 20 Chinese children with HSPN and 30 controls in present study. The genetic analyses revealed 3 polymorphisms (954T > C heterozygous, 1038A > G heterozygous and homozygous, all in exon 8) in 7 out of 20 patients studied, but there was no significant difference in the genotypic and allelic frequencies of these polymorphisms between the patients and controls. The result did not support the possible role of the NPHS2 gene in susceptibility to HSPN in the population studied. Studies in a larger sample population with different genetic backgrounds will be necessary in the future.

The role of chemokines in Henoch Schonlein Purpura

The pathogenesis of Henoch Schonlein Purpura is incompletely understood and the role of chemokines is unknown. To investigate the levels of CC chemokines, eotaxin, TARC, and CXC chemokine IP-10 in Henoch Schonlein Purpura. Three groups of children were enrolled in the study: Henoch Schonlein Purpura in active stage (n = 26), Henoch Schonlein Purpura in remission phase (n = 26) and healthy children (n = 18). Levels of eotaxin, TARC, and IP-10 were determined in plasma using ELISA. No significant difference was observed in the plasma level of eotaxin and TARC levels between the HSP and healthy children (>0.05). We could not find any significant difference between acute phase of the disease and convalescent phase in eotaxin and TARC levels (P > 0.05). We have suggested significant decreases in plasma IP-10 in the acute phase of the disease compared with the convalescent phase (P < 0.05). There was a significant difference in IP-10 levels between active stage and healthy controls, too (<0.05). We could not find any significant correlation between chemokine levels and system involvement (>0.05). Our study shows that plasma level of eotaxin and TARC levels do not differ between the HSP and healthy children. But, decreasing the release of the Th1 chemokine IP-10 in HSP active stage may show that in HSP, there is no shift to Th1 lymphocytes in children with HSP. Further investigations are warranted to more fully explore and understand the production of and potential role of these chemokines in HSP.

Antiphospholipid antibodies in children with Henoch–Schonlein purpura: a prospective study from North India

Henoch–Schonlein purpura (HSP) is a small‐vessel vasculitis affecting the skin, gastrointestinal tract, and kidneys [1]. Autoimmunity may have a role in the pathogenesis of HSP [1], [2]. Antiphosph...

Leptin levels in Henoch–Schönlein purpura

The objective of this paper is to assess the possible role of nitric oxide (NO) and leptin in Henoch-Schönlein purpura (HSP). We investigated the serum leptin and total nitrite levels in 22 children with HSP in the acute phase and after remission and in 20 age- and sex-matched healthy control. Serum leptin levels (nanograms per milliliter; median, min-max) were statistically higher in the acute phase (12.9, 9.1-19.5) than those in the remission phase (6.1, 3.7-10.5, p<0.001) and in the control group (4.9, 3.8-7.5, p<0.001). Also, serum nitrite levels (micromole per liter; median, min-max) were higher in children in the acute phase (45.0, 32.0-60.0) compared to those in remission phase (30.5, 23.0-48.0) and in the control group (29.5, 18.0-38.0) (p<0.001, p<0.001, respectively). There was a positive correlation between serum leptin and total nitrite levels (r=0.65, p<0.001). We have demonstrated that serum leptin and NO levels were increased during the acute phase in children with HSP, and returned to normal levels in remission. We suggest that leptin and NO may have a role in the immunoinflammatory process of HSP, especially in the acute phase. Further studies are needed to clearly establish the roles of leptin and NO in the pathogenesis of HSP.

Henoch Schonlein Purpura in Childhood

Henoch Schonlein purpura (HSP) is one of the most common vasculitis in childhood characterized by nonthrombocytopenic purpura, abdominal pain, arthritis, and glomerulonephritis. Depending on the anatomical sites of involvement many other manifestations including every other organ of the body can be seen. However the most important involvement determining the longterm prognosis is the severity of renal disease. The pathogenesis of HSP is not clear, but it is believed to be an immunoglobulin-mediated inflammatory process resulting from immune complex reaction to various antigenic stimuli. Although none of them has been confirmed to be the exact cause, many bacterial, viral and parasitic infections, insect bites, vaccinations, and exposure to drug and dietary allergens have been described as triggering factors for HSP. Immune complexes are deposited in the vascular walls and mesangium triggering the mediators of inflammation. Treatment of HSP is supportive, and a clear advantage of glucocorticoids over supportive therapy has not been shown in the management of the disease except rapidly progressive type of glomerulonephritis. In this article the epidemiological, clinical and pathogenetic features, current treatment strategies, and outcome of the disease will be reviewed. Keywords: henoch-schonlein purpura, childhood, clinical manifestations, pathogenesis, treatment, prognosis

Clinical approach to cutaneous vasculitis

This review provides the readers with an update on the clinical approach of a patient seeking treatment with cutaneous vasculitis. It outlines the work-up for assessing patients with cutaneous vasculitis and discusses the essential features of the main conditions included within this category. Recent works on genetic and infectious factors implicated in the pathogenesis of Henoch-Schonlein purpura are discussed. Special attention is given to the prognosis and response to treatment. Also, recent reports on cutaneous vasculitis secondary to connective tissue diseases are reviewed. With this review, the reader will be able to establish the steps to be followed in the clinical approach to a patient seeking treatment with cutaneous vasculitis.

Adrenomedullin and total nitrite levels in children with Henoch-Sch�nlein purpura

Nitric oxide (NO) is synthesized from endothelium and has an important role in the control of vascular tonus. Adrenomedullin (AM) is a potent vasodilator, and cytoprotective peptide is produced not only in adrenal medulla, but also in the vascular smooth muscle and endothelial cells. To investigate the endothelial synthesis of AM and NO, and endothelial injury in Henoch-Schönlein purpura (HSP), we measured their levels in 16 children with HSP, who were evaluated during the acute and remission phases, and compared with 12 healthy controls. Plasma AM levels (pmol/ml) were significantly higher in acute phase children (46.87+/-11.49) than in those in remission (35.59+/-12.39, p<0.01) and controls (30.70+/-9.12, p<0.001). Similarly, plasma total nitrite levels (mumol/l) were higher in acute phase patients (47.50+/-12.30) than in those in remission (35.94+/-10.08, p<0.005) and controls (34.56+/-11.51, p<0.05). Urinary excretion of AM (pmol/mg creatinine) was higher in acute phase patients (53.85+/-23.22) than in remission patients (29.97+/-9.33, p<0.01) and controls (37.43+/-15.78, p<0.05). Patients had increased urinary nitrite excretion (mumol/mg creatinine) in acute phase (2.39+/-1.18) compared to those in remission (1.53+/-0.90, p<0.05) and controls (1.05+/-0.61, p<0.005). There was no significant difference between remission phase and controls in AM and nitrite levels ( p>0.05). This study concluded that AM and NO may have a role in the immunoinflammatory process of HSP, especially in the active stage, although whether this perpetuates, or protects against, further vascular injury is not clear. Further studies are needed to clearly establish the roles of AM and NO in the pathogenesis of HSP.

Endothelin levels in Henoch-Schonlein purpura

Henoch-Schonlein purpura (HSP) is one of the most common types of vasculitis disorders seen in childhood and is characterized by a rash, arthritis, abdominal pain, and renal involvement. Although HSP is an immunoglobulin A (IgA) related immune complex disease, the pathogenesis has not been fully elucidated. Cytokines have been implicated in the pathogenesis, but endothelins (ET) - vasoconstrictor hormones produced by endothelial cells - have not been studied in patients with HSP. In a controlled study, we measured ET-1 levels in children with HSP during the acute and remission phases. ET-1 levels were significantly higher in the HSP patients during the acute phase compared with the control group and the HSP patients in the remission phase. There was no correlation between ET-1 levels and disease severity, acute phase reactant response, or morbidity. The role of endothelins and other cytokines in the pathogenesis of HSP needs to be further explored.

Nitric oxide in Henoch-Scho¨nlein purpura

Objective : To assess the value of nitric oxide (NO) production on the disease activity in children with Henoch-Schönlein purpura (HSP) by measuring serum nitrate levels and urinary nitrate excretion as an indicator for NO production. Methods : The study group consisted of 25 patients and 20 healthy children. We measured serum nitrate, urinary excretion of nitrate, and CRP levels in the acute phase and after remission. Results : Serum nitrate levels in the acute phase of the disease were found to be increased compared to the remission phase (28.67 - 10.3 mmol/l, 14.16 - 2.02 mmol/l) (p<0.001) and the control group (13.15 - 2.28 mmol/l) (p<0.001). Urinary nitrate excretion in the acute phase of the patients (15.32 - 9 mmol/mg) was increased compared to that in the remission phase (8.26 - 4.3 mmol/mg) (p=0.016) and in the control group (7.24 - 4.9 mmol/mg) (p<0.01). Conclusion : Serum NO and urinary nitrate excretion were found to be elevated in patients with HSP and this increase was associated with activation of the disease rather than its severity. These findings suggest a role for NO in the pathogenesis of HSP, but nitric oxide in HSP should be further studied in order to elucidate the pathophysiology of the disease

Henoch-Schönlein purpura.

Although Henoch-Schönlein purpura (HSP) can occur at any age from infancy to adulthood, it is overwhelmingly a disease of childhood. Indeed, HSP is the most common vasculitis syndrome affecting children. The clinical features of HSP have been well documented, and the diagnosis is generally not difficult. However, there are substantial gaps in our understanding of the etiology, pathogenesis, and treatment of HSP. This article briefly reviews the clinical aspects of HSP and new information concerning therapy. The major focus of this review is recent information concerning abnormalities of immunoglobulin A1 glycosylation and the role of aberrantly glycosylated immunoglobulin A1 in the pathogenesis of HSP.

Role of free oxygen radicals and prostanoids in the pathogenesis of Henoch-Schönlein Purpura

The pathogenesis of Henoch-Schönlein Purpura (HSP) is still controversial. The aim of our study was to investigate the role of oxidative stress and cyclooxygenase (CO) pathway products in the pathogenesis of HSP. In order to investigate this, malondialdehyde (MDA) levels, indicating lipid peroxidation, prostaglandin E (PGE)-like activity as inflammatory mediator and vitamin E (vit-E) levels indicating anti-oxidant status were studied in a group of 10 children with HSP (five girls and five boys, aged 6–21 years, mean 10.7 years), both in the acute and recovery phase of the disease and in five age and sex-matched healthy children as a control group. The patients were also grouped into low and high clinical score groups. Plasma levels of MDA and PGE-like activity were significantly elevated in the active phase of HSP compared to the recovery phase. Vit-E levels were significantly reduced in the active phase compared to the recovery phase. The plasma levels of PGE-like activity of the patients obtained in the active phase were significantly higher than the levels of the control group, whereas the levels of the recovery phase were significantly lower than in the control group. No such difference between the controls and MDA and vit-E levels in the patient group was shown. No correlation between the clinical scores and the parameters studied could be found. Our findings indicate that oxidant stress and CO pathway products may play a role in the pathogenesis of HSP.

Erythrocyte superoxide dismutase activity and plasma malondialdehyde levels in children with Henoch Schönlein purpura

Reactive oxygen molecules (ROM) have been suggested to contribute to many pathological conditions including vasculitides and renal diseases. In the present study we measured the activity of superoxide dismutase (SOD) as an antioxidant enzyme in red blood cells and the level of malondialdehyde (MDA), which is a product and an indicator of lipid peroxidation, in the plasma of 16 children (7M, 9F) with Henoch Schönlein purpura (HSP) at the onset of the disease (SOD 1 and MDA 1) and at the remission period (SOD 2 and MDA 2). The results were compared with the results of 17 healthy children studied as a control group. There was no significant difference for SOD activities between the patients in each period and the control group (p &gt; 0:05). There was a statistically significant difference between MDA 1 and MDA 2 levels (p &lt; 0:01), each of which were also significantly different from the MDA levels of control group (p &lt; 0:001 and p &lt; 0:01, respectively). The effect of ROMs on different clinical conditions of HSP was also examined and lipid peroxidation was found to be increased more in patients with renal involvement. It is concluded that oxidant stress especially lipid peroxidation plays an important role in the pathogenesis of HSP and in development of renal injury.

Erythrocyte superoxide dismutase activity and plasma malondialdehyde levels in children with Henoch Schönlein purpura.

Reactive oxygen molecules (ROM) have been suggested to contribute to many pathological conditions including vasculitides and renal diseases. In the present study we measured the activity of superoxide dismutase (SOD) as an antioxidant enzyme in red blood cells and the level of malondialdehyde (MDA), which is a product and an indicator of lipid peroxidation, in the plasma of 16 children (7M, 9F) with Henoch Schönlein purpura (HSP) at the onset of the disease (SOD 1 and MDA 1) and at the remission period (SOD 2 and MDA 2). The results were compared with the results of 17 healthy children studied as a control group. There was no significant difference for SOD activities between the patients in each period and the control group (p > 0.05). There was a statistically significant difference between MDA 1 and MDA 2 levels (p < 0.01), each of which were also significantly different from the MDA levels of control group (p < 0.001 and p < 0.01, respectively). The effect of ROMs on different clinical conditions of HSP was also examined and lipid peroxidation was found to be increased more in patients with renal involvement. It is concluded that oxidant stress especially lipid peroxidation plays an important role in the pathogenesis of HSP and in development of renal injury.

Eosinophil cationic protein in Henoch-Schönlein purpura and in IgA nephropathy

In order to identify the relationship between eosinophil activation in Henoch-Schönlein purpura (HSP) and IgA nephropathy, serum eosinophil cationic protein (ECP) was analyzed in both conditions. The soluble interleukin-2 receptor (sIL-2R) was also analyzed. The levels of ECP were significantly higher in HSP patients (mean 9.7 +/- 1.8 microg/l) than in a control group (mean 4.6 +/- 0.7 microg/l). When the HSP patients were classified into two groups, one with normal urine and one with abnormal urine, the latter showed higher levels of ECP than the former. Levels of ECP were not significantly higher in IgA nephropathy patients than in a control group. The sIL-2R levels were elevated in the serum of HSP and IgA nephropathy patients compared with controls. In conclusion, eosinophil activation may be involved in the pathogenesis of HSP but not in IgA nephropathy.

Complement activation in Henoch-Schönlein purpura.

The pathogenetic mechanism underlying Henoch-Schönlein purpura (HSP) is poorly understood. Complement activation has been thought to have a role, but despite the demonstration of complement components in skin and renal biopsy material, serological evidence of complement activation is not convincing. We have assessed complement activation in 64 children with acute HSP. We used an enzyme-linked immunosorbent assay to measure plasma levels of three multimolecular complement activation protein (CAP) complexes: C1r:C1s:C1-inhibitor, C3bP and C5b-9. We found no significant difference between the levels of CAPs in children with acute HSP and a control group of children. This study does not support a role for complement activation in the pathogenesis of HSP.

ALTERATIONS IN THE O-LINKED GLYCOSYLATION OF IgA1 IN CHILDREN WITH HENOCH-SCHONLEIN PURPURA. • 1848

IgA plays a central role in the immunopathogenesis of Henoch-Schonlein purpura (HSP). Although there are two subclasses of IgA, HSP is associated with abnormalities involving only IgA1, but not IgA2. The reasons for the exclusive involvement of IgA1 in the pathogenesis of HSP remain unclear. One important difference between IgA1 and IgA2 is that IgA1 contains a heavily glycosylated hinge region between the CH1 and CH2 domains of the heavy chain. The hinge region oligosaccharides of IgA1 consist of galactose (Gal) plus N-acetylgalactosamine (GalNAc) which is O-linked to serine or threonine. Approximately 75% of the Gal residues are sialylated. Thus, the typical glycosylation pattern is Serine - GalNAc - Gal - Sialic acid. IgA2 contains no heavy chain hinge region, and therefore no O-linked glycosylation sites. The present study was performed to examine the O-linked glycosylation of IgA1 in 28 children with HSP and 26 control children. Plant lectins with the following binding specifities were used: Table The binding of each lectin to serum IgA1 was measured by enzyme immunoassay. There was no difference in the binding of Jacalin to IgA1 from HSP patients compared to controls (P = 0.5). The binding of Peanut lectin to IgA1 was significantly greater in HSP patients compared to controls (P = 0.007). Since sialic acid inhibits the binding of Peanut lectin to GalNAc - Gal, these results suggest there was less sialic acid in the O-linked oligosaccharides of IgA1 from patients with HSP compared to controls. Indeed, the binding of the sialic acid specific Elderberry lectin to IgA1 was significantly lower in HSP patients compared to controls (P = 0.004). The results of this study indicate that the O-linked oligosaccharides of IgA1 from patients with HSP are deficient in sialic acid. This alteration in the glycosylation of IgA1 may explain the exclusive involvement of IgA1 in HSP, and account for many of the immunologic and histologic features of the syndrome.

Henoch-Schonlein purpura: clinical experience and contemplations on a streptococcal association.

Henoch-Schonlein Purpura (HSP) is a common cause of vasculitis in children. The role of an antecedent streptococcal infection is still controversial. The aim of this study is to verify such a relationship, as well as to provide a profile of the clinical features and the magnitude of this disorder in Jordan. We identified 69 cases of HSP below the age of 13 years between January 1991 and April 1994 admitted to the two main hospitals in northern Jordan. Thirty-five of these cases were prospectively enrolled during the last year of the study. Forty-three controls, frequency-matched to the cases on age and sex, were selected from the out-patient clinics of the same two hospitals. The minimum estimate of the annual incidence was 8.5/100,000. All patients recovered completely and were well after a mean period of follow-up of 16 months. The clinical features were essentially similar to those reported by others. Unusually, two of our cases followed mumps and one occurred after otitis media caused by Streptococcus pneumoniae. Forty-nine per cent of all patients in this series had evidence of a recent streptococcal infection (elevated antistreptolysin O titre) compared to 16 per cent of the controls. The difference was statistically significant (P = 0.004). This finding supports a role for antecedent streptococcal infection in the pathogenesis of HSP.

The absence of anti-neutrophil cytoplasmic antibodies in patients with Henoch-Schönlein purpura.

Sera from 14 patients with acute Henoch-Schönlein purpura (HSP) and 5 patients with a past history of HSP were assessed using a immunofluorescence technique for the presence of IgG, IgA, and IgM anti-neutrophil cytoplasmic antibodies (ANCA). There was no evidence of IgG, IgA, or IgM ANCA in the sera of these patients. These results suggest that ANCA are not involved in the pathogenesis of HSP.