Henoch-Schönlein Purpura Nephritis Patients Research Articles

Expression of Acid-Sensing Ion Channels in Renal Tubular Epithelial Cells and Their Role in Patients with Henoch-Schönlein Purpura Nephritis.

BackgroundAcid-sensing ion channels (ASICs) are ligand-gated cation channels activated by extracellular protons. However, the role of ASICs in kidney diseases remains uncertain. This study investigated ASICs expression in kidney tissues and their role in the development of Henoch-Schönlein purpura nephritis (HSPN).Material/MethodsThe expression of ASIC subunits was examined by immunochemical techniques in the kidney tissue from HSPN patients. Acid-induced ASICs expression in cultured renal tubular epithelial cells was determined by quantitative RT-PCR analysis. The expression of K7 and K18 protein in renal tubular epithelial cells was used to evaluate acid-induced cell injury. In addition, we observed the effect of blocking ASICs on acid-induced cell injury to assess the role of ASICs in renal tubular epithelial cell injury.ResultsThe results showed that ASIC1, ASIC2, and ASIC3 proteins were obviously expressed in renal tubular cells from HSPN patients. ASIC1 expression and 24-h urine protein level were higher in the pathological grade ISKD III group than in the ISKD II group. ASIC1, ASIC2, and ASIC3 mRNA, and K7 and K18 protein expression in cultured renal tubular epithelial cells were increased when exposed to pH 6.5. K7 and K18 protein expression was closely related to ASIC1 expression, and ASICs blockers reduced K7 and K18 protein expression in tubular epithelial cells.ConclusionsThese findings suggest ASICs are most highly expressed in renal tubular cells of HSPN patients, which is closely related to renal tubular injury. ASICs might be involved in the development of HSPN.

Clinical effects of leflunomide in the treatment of patients with Henoch-Schonlein purpura nephritis who were not response to cyclophosphamide

Objective To evaluate the effect of leflunomide(LEF) in the treatment of adult Henoch-Schonlein purpura nephritis(HSPN) patients with nephrotic syndrome who were not response to cyclophosphamide. Methods 26 patients with nephrotic syndrome HSPN performance treated by CTX therapy, relapse or discontinued due to adverse reactions were selected.LEF joint glucocorticoid treatment was given to the patients for 6 months.Collected the blood routine, urine routine, 24 hours urine protein, urinary red blood cell count, serum albumin, hepatic and renal functions before treatment and 6 months after treatment, and the adverse drug reactions were recorded. Results In 26 patients, 20 cases had clinical remission.After treatment, compared with before treatment, the urinary protein, urinary red blood cell count decreased significantly(P<0.05), and serum albumin increased significantly(P<0.05) in 20 patients, renal function recovered to normal in 6 patients.11 patients achieved complete remission, 9 patients achieved partial remission.Compared with cyclophosphamide treatment was invalid, the clinical remission rate was 76.9%(χ2=6.783, P<0.01). Of 26 patients, 1 patient had mild gastrointestinal symptoms, 1 patient had mild neutropenia, 1 patient had mild liver transaminases elevated, compared with cyclophosphamide side effects incidence rate of 46.2%(12/26), the incidence rate of adverse reactions was 11.5%(3/26)(χ2=5.496, P<0.05), they were relieved after expectant treatments, no patients stop treatment. Conclusion LEF combined with glucocorticoid had good efficacy and mild adverse reactions for adult HSPN patients with nephrotic syndrome. Key words: Purpura, Schoenlein-Henoch; Nephritis; Leflunomide; Cyclophosphamide

Effect of CD40/CD40L signaling on IL-10-producing regulatory B cells in Chinese children with Henoch-Schönlein purpura nephritis.

The aim of the present study was to examine the role and mechanism of interleukin-10 (IL-10)-producing regulatory B cells (B10 cells) in the pathogenesis of Henoch-Schönlein purpura nephritis (HSPN). We examined the percentage of B10 cells, CD19+CD24hiCD38hi B cells, CD19+CD24hiCD27+ B cells, Th17 cells, and T regulatory (Treg) cells within the peripheral blood mononuclear cell (PBMC) population in healthy subjects and HSP/HSPN patients. The percentage of B10 cells and CD19+CD24hiCD38hi B cells was reduced in HSPN patients and that of CD19+CD24hiCD27+ B cells was decreased only in HSPN patients with hematuria and proteinuria or massive proteinuria. The expression of IL-10 by B10 cells and their subsets was decreased in HSPN patients and returned to normal levels in HSP/HSPN patients in remission. B10 cells and their subsets negatively correlated with the Th17/Treg ratio. There was no difference in B10pro + B10 cells, Th17 cells, Treg cells, and the Th17/Treg ratio between children with HSP/HSPN and healthy controls after CD40L stimulation. On the other hand, the level of IL-10 expressed by CD19+CD40+ B cells was decreased in HSPN, and the percentage of B10pro + B10 cells and Treg cells was reduced and that of Th17 cell was increased in the presence of anti-CD40L monoclonal antibody (mAb). Thus, decreased B10 cells and CD19+CD24hiCD38hi B cells may function as an early marker of renal impairment in HSPN. The dysfunction of B10 cells may play a role in the pathogenesis of HSPN by regulating the Th17/Treg balance. Moreover, the CD40/CD40L signaling pathway may play a role in B10 cell differentiation and functional maturation.

Differences in pathological characteristics and laboratory indicators in adult and pediatric patients with Henoch-Schönlein purpura nephritis.

We aimed to investigate the differences in renal histopathological changes and laboratory parameters between adult and pediatric patients with Henoch-Schönlein purpura nephritis (HSPN), and to analyze the correlation between laboratory parameters and renal histopathological grading. A total of 139 patients diagnosed with HSPN between September 2010 and December 2014 at the First Hospital of Jilin University, China, were retrospectively reviewed. The clinical and pathological characteristics were examined and compared between the adult and the pediatric patients. A majority of adult (75.0%) and pediatric (66.2%) patients were categorized as pathological grade III HSPN. Adults having crescent lesions, interstitial fibrosis and renal artery involvement significantly outnumbered child counterparts (all P<0.05). Pathological grading showed a positive correlation with 24-h urine protein (r=0.307, P=0.009), microalbuminuria (r=0.266, P=0.000) and serum globulin (r=0.307, P=0.014), and a negative correlation with serum albumin (r=0.249, P=0.037) in pediatric patients with HSPN. Among adult patients with HSPN, histopathological grading showed a positive correlation with 24-h urine protein (r=0.294, P=0.015), microalbuminuria (r=0.352, P=0.006), α1-microglobulin (r=0.311, P=0.019) and immunoglobulin G (r=0.301, P=0.023) in urine, and serum creatinine (r=0.292, P=0.018). Further, a negative correlation between serum albumin and pathological grading was also observed (r=0.291, P=0.018). In conclusion, the severity of renal pathological lesions in HSPN patients is well reflected by the levels of proteinuria. Adult patients have more severe renal histopathological changes than pediatric patients.

A higher frequency of CD4+ CXCR5+ T follicular helper cells in patients with newly diagnosed Henoch–Schönlein purpura nephritis

T follicular helper (TFH) cells play an important role in the humoral immune responses. The aim of this study was to examine the frequency of different subsets of CD4+CXCR5+ TFH cells and B cells in patients with new-onset Henoch–Schönlein purpura nephritis (HSPN). The numbers of different subsets of CD4+CXCR5+ TFH cells, B cells and the constituents of serum cytokines were detected in a total of 25 patients with newly diagnosed HSPN before and after treatment, and in 14 healthy controls (HC). The potential connection of these cells with the clinical characteristics in HSPN patients was analyzed. The numbers of circulating CD4+CXCR5+, CD4+CXCR5+ICOS+ and CD4+CXCR5+PD-1+ TFH cells, CD86+CD19+, CD38+CD19+ B cells and serum IL-2, IL-4, IL-17A, IL-21 and IFN-γ were significantly higher in HSPN patients (p<0.05) than in HC. Before and after treatment the numbers of CD4+CXCR5+ TFH cells were negatively correlated with the values of eGFR (r=−0.7162, p<0.05; r=−0.732, p<0.05, respectively). Similarly the numbers of CD4+CXCR5+PD-1+ TFH cells were negatively correlated with 24-h urinary proteins (r=−0.4013, p<0.05; r=−0.7857, p<0.05, respectively), and the numbers of CD4+CXCR5+ICOS+ TFH cells were positively correlated with the levels of serum IL-21 (r=0.5186, p<0.05; r=0.8503, p<0.05, respectively) and 24-h urinary protein (r=0.6045, p<0.05; r=0.833, p<0.05, respectively) in these patients, regardless of treatment. Following treatment the numbers of CD4+CXCR5+, CD4+CXCR5+PD-1+, and CD4+CXCR5+ICOS+ TFH cells, as well as serum levels of IL-21 were significantly reduced, however IL-4 levels were noticeably increased (p<0.05). A higher frequency of circulating CD4+CXCR5+ TFH cells existed in patients with HSPN and may be a viable therapeutic target.

Association of gene polymorphism in interleukin-4 and interleukin-13 gene with Henoch-Schonlein purpura

Objective To investigate the association between 2 single nucleotide polymorphisms(SNPs) [rs2243250 in interleukin(IL)-4 gene and rs1800925 in IL-13 gene] in Henoch-Schonlein purpura (HSP)and Henoch-Schonlein purpura nephritis (HSPN) in Han Chinese children.The level of IL-4 and IL-13 in serum were compared between HSP and HSPN. Methods A case-control study was adopted in this research, and 383 children with HSP or HSPN were recruited in this study, 409 normal children served as controls.The genotypes of 2 SNPs were detected by using polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP), and the serum levels of IL-4 and IL-13 in HSP and HSPN patients were detected by using enzyme linked immunosorbent assay(ELISA). All the data were analyzed by SPSS 16.0 software. Results (1)There was no association (polymorphism of SNP rs2243250 in IL-4 gene) in HSP group and HSPN group compared with the healthy control group (P>0.05); and the polymorphism of another SNP(rs1800925 in IL-13 gene) was associated with HSP (P=0.037), and the frequency of T allele of the study group was higher than that of the healthy control group (P=0.027). But there was no difference between the study group (HSP group and HSPN group) and the healthy control group in frequency of TT genotype(P=0.132), and there was no association between HSPN group and healthy control group (P=0.487); also there was no association between polymorphism of this SNP in HSP group and HSPN group (P=0.129). (2)There was an association between polymorphism of IL-13 gene and IL-13 level in serum, patients with TT genotype had a higher serum IL-13 level than any other genotypes(P 0.05). (3)There was an association between polymorphism of IL-13 gene and IL-13 level in serum patients with HSPN who had a higher level of serum IL-13 than the patients with HSP (P<0.05), but there was no difference in serum IL-4 level between HSP group and HSPN group. Conclusions The polymorphism of SNP (rs1800925 in IL-13 gene) was associated with HSP group, and the polymorphism of this SNP might affect the level of IL-13 in serum.The patients with HSPN have a higher level of serum IL-13 than the patients with HSP, and high level of IL-13 may be a risk factor in the progression from HSP to HSPN. Key words: Henoch-Schonlein purpura; Henoch-Schonlein purpura nephritis; Interleukin-4; Interleukin-13; Gene polymorphism

24h Urinary Protein Levels and Urine Protein/Creatinine Ratios Could Probably Forecast the Pathological Classification of HSPN.

This study aimed to assess the relevance of laboratory tests in Henoch-Schönlein purpura nephritis (HSPN) classification, and determine accurate classification factors. This prospective study included 694 HSPN patients who underwent ultrasound-guided percutaneous renal biopsy (PRB). Renal specimens were scored according to International Study of Kidney Disease in Children (ISKDC) classification. Meanwhile, blood samples were immediately collected for laboratory examination. The associations between laboratory parameters and HSPN classification were assessed. Significant differences in levels of serum Th1/Th2 cytokines, immunoglobulins, T-lymphocyte subsets, complement, and coagulation markers were obtained between HSPN patients and healthy children. Interestingly, 24h urinary protein (24h-UPRO) levels and urine protein/urine creatinine ratios could determine HPSN grade IIb, IIIa, and IIIb incidences, with areas under ROC curve of 0.767 and 0.731, respectively. At 24h-UPRO >580.35mg/L, prediction sensitivity and specificity were 75.2% and 70.0%, respectively. These values became 53.0% and 82.3%, respectively, with 24h-UPRO exceeding 1006.25mg/L. At urine protein/urine creatinine > 0.97, prediction sensitivity and specificity were 65.5% and 67.2%, respectively, values that became 57.4% and 80.0%, respectively, at ratios exceeding 1.2. Cell and humoral immunity, coagulation and fibrinolytic systems are all involved in the pathogenesis of HSPN, and type I hypersensitivity may be the disease trigger of HSPN. 24h-UPRO levels and urine protein/creatinine ratios could probably forecast the pathological classification of HSPN.

Methylprednisolone pulse therapy and intravenous cyclophosphamide therapy combined with cocktail therapy in severe pediatric Henoch-Schönlein purpura nephritis patient.

Henoch-Schönlein purpura (HSP) is a common self-limited vasculitis in children. The long-term prognosis depends on renal involvement. In severe Henoch-Schönlein purpura nephritis (HSPN) patients, >50 % have crescent formation and nephrotic syndrome that are important predicted outcomes. Therefore, for such patients, an aggressive immunosuppressive therapy is needed to prevent the progression. However, there is no consensus for an appropriate therapeutic regimen for severe pediatric HSPN patients. In this paper, we have reported on a 6-year-old boy who presented with HSPN with nephrotic syndrome and severe histopathological abnormalities; he was diagnosed with International Study of Kidney Disease in Children (ISKDC) grade IVb. Despite treatment with methylprednisolone pulse therapy, followed by oral prednisolone and dipyridamole; the nephrotic syndrome persisted. Subsequently, intravenous cyclophosphamide therapy (IVCY) (500–1,000 mg m−2 once a month for 7 months; total 6,000 mg m−2) was administered, followed by azathioprine and enarapril. Within 7 months of disease onset, complete remission was achieved. After 22 months of the initial renal biopsy, the second biopsy was performed to confirm treatment efficacy. Histopathological findings improved, and ISKDC grade IIIa was diagnosed. Even after 5 years of HSPN onset, complete remission and normal renal function is maintained. Although our evidence is restricted to single patient, we have shown that MPT and IVCY combined with cocktail therapy may be an effective treatment for severe pediatric HSPN.

Association study of ACE and eNOS single nucleotide polymorphisms with Henoch-Schönlein purpura nephritis

Previous studies have shown that insertion/deletion polymorphisms in the angiotensin-converting enzyme (ACE) gene and the endothelial nitric oxide synthase (eNOS) gene are associated with Henoch-Schönlein purpura nephritis (HSPN). However, further studies are required to prove the relationship between HSPN and ACE and eNOS single nucleotide polymorphisms (SNPs). We studied six ACE SNPs and two eNOS SNPs by genotyping HSPN patients. Statistical analyses indicate that four ACE SNPs and two eNOS SNPs are associated with HSPN susceptibility. A cumulative effect analysis suggested that an increased number of unfavourable genotypes may lead to an increased risk of HSPN. By comparing alleles, genotypes and haplotypes that are associated with lupus nephritis (LN) and HSPN, we found genetic heterogeneity between HSPN and LN.

C1GALT1 polymorphisms are associated with Henoch–Schönlein purpura nephritis

Henoch-Schönlein purpura nephritis (HSPN) is the most serious long-term complication of Henoch-Schönlein purpura and aberrant galactosylation of IgA1 plays a role in its development. However, the precise role of genetic factors contributing to the abnormal IgA1 galactosylation remains unknown. In order to examine the effects of C1GALT1 gene encoding core 1 β1,3-galactosyltransferase, an important role in the β1,3 glycosylation of IgA1, on HSPN susceptibility, we conducted a case-control association genetic study in 269 HSP and 61 HSPN in China. Five tagging SNPs, SNP1(-734 C/T), SNP4(-465A/G), SNP6(-330 G/T), SNP7(-292 C/-), and SNP8(1365 G/A) in C1GALT1 were studied using single-locus and haplotype-based multilocus analysis. Our results demonstrated that 1365 G allele frequency was significantly higher in HSPN patients than in HSP patients without nephritis (0.459 vs 0.331, p = 0.0008, adjusted p' = 0.004) with an odds ratio (OR) = 1.716, 95%CI 1.151-2.560). The GG genotype of 1,365 G/A was significantly different in HSP without nephritis and HSPN (p = 0.008, adjusted p'' = 0.04). We did not observe statistically significant differences in haplotype frequencies between HSPN and HSP patients. In conclusion, our study suggested that the 1365 G/A polymorphism of the C1GALT1 gene may contribute to HSPN development.

Henoch–Schönlein nephritis with nephrotic state in children: predictors of poor outcomes

Nephritis develops in 18–81% of Henoch-Schonlein purpura patients, and the long-term outcomes of this nephritis show great variation. A nephrotic state at disease onset has been proposed as a predictor of poor renal outcomes. We studied 42 children with Henoch-Schonlein purpura nephritis (HSPN) who presented with a nephrotic state during the early phase of the disease. The median age of the patients at the time of diagnosis was 7.4 years. The median follow-up period was 6.2 years. Twenty-five children (60%) made a complete recovery; nine (21%) progressed to end-stage renal disease. Multivariate logistic regression analyses revealed that the nephrotic state lasting for more than 3 months had a significant effect on renal outcomes (odds ratio 11.6; 95% confidential interval, 1.16–348.4; p = 0.03), whereas initial renal insufficiency, renal pathological findings, age at onset, and types of treatment did not. These findings indicate that clinical presentation, particularly duration of the nephrotic state, is related to long-term outcomes in HSPN patients with nephrosis. Our results also indicate that the therapeutic options for HSPN patients with a nephrotic state should be based on the clinical presentation rather than on the initial pathological findings alone.

The role of serum myeloid-related protein 8/14 complex in Henoch–Schönlein purpura nephritis

Myeloid-related protein (MRP) 8/14 complex is a marker of monocyte and neutrophil activation. We evaluated whether serum MRP8/14 complex is associated with clinical manifestations and pathological findings of Henoch-Schönlein purpura nephritis (HSPN). Patients were divided into two groups based on serum MRP8/14 complex levels at renal biopsy. Group 1 consisted of 18 HSPN patients with less than median (670 ng/ml) MRP8/14 complex levels, and Group 2 of 12 HSPN patients with greater than median levels. Clinical manifestations, laboratory findings and serum E-selectin levels, as a marker of vascular endothelial cell dysfunction, as well as histological and immunohistochemical findings were investigated for both groups. We also measured MRP8/14 complex levels in disease control and healthy control children. Urinary protein excretions, serum MRP8/14 complex levels, and serum E-selectin levels were all higher in Group 2 than in Group 1 patients. Serum MRP8/14 complex levels were higher in HSPN patients than in controls. Serum MRP8/14 complex levels were strongly associated with serum E-selectin levels. Pathological findings revealed that the proportions of patients with ISKDC grades III, IV and V in Group 2 were higher than in Group 1. Our findings suggest that serum MRP8/14 complex levels might be associated with the severity of renal injury and endothelial cell dysfunction in HSPN patients.

Improved Outcome of Henoch-Schonlein Purpura Nephritis by Early Intensive Treatment

To evaluate the different therapies used to treat mild, moderate and severe Henoch-Schonlein purpura nephritis (HSPN) patients and to identify the most effective treatment. One hundred and eighty six children were evaluated retrospectively. They were divided into mild, moderate and severe condition groups. Different therapeutic protocols of non-steroid therapy, hydrocortisone sodium succinate (HCSS) therapy, methylprednisolone (MP) pulse therapy, and MP in combination with tripterygium glycoside (TG) therapy were used to treat the different groups. After 4 wk, in the mild group, patients were more likely to respond to HCSS therapy than non-steroid therapy (P < 0.05). Moderate HSPN patients were more likely to respond to MP therapy than HCSS therapy (P < 0.05). Severe HSPN patients were more likely to respond to MP in combination with TG than single MP therapy (P < 0.05). At last follow-up, all children had normal urinalysis, blood pressure and serum urea and creatinine. In the mild group, the mean duration of proteinuria was shorter in HCSS therapy group than in non-steroid therapy group (P < 0.05). In the moderate group, the mean duration of proteinuria was shorter in MP pulse therapy group than in HCSS therapy group (P < 0.05). The present study has demonstrated a superior effect of HCSS therapy in patients with mild HSPN disease, of MP therapy in patients with moderate disease, and of MP in combination with TG therapy in patients with severe disease. Intensive therapy administered initially reduces the duration of urinary protein abnormality.

Clinical outcomes in children with Henoch–Schönlein purpura nephritis grade IIIa or IIIb

Henoch-Schönlein purpura (HSP) is one of the most common causes of systemic vasculitis in children. The incidence of HSP nephritis (HSPN) among HSP patients has been reported to be 15-62%. Even so, what constitutes severe HSPN is controversial. In the study reported here, we retrospectively reviewed the clinical features and prognosis of 101 children with HSPN, ISKDC grade IIIa/IIIb, from January 1992 to November 2008. Patients with isolated hematuria and/or proteinuria <50 mg/kg/day received triptolide alone, and those with nephrotic range proteinuria received a combination therapy of prednisone and triptolide. Nephrotic syndrome was the most common clinical manifestation (45.5%). There were no significant differences in the clinical features (χ(2) = 2.756, P = 0.252), the side effects related to treatment (χ(2) = 2.259, P = 0.894), prognosis between IIIa and IIIb (χ(2) = 3.013, P = 0.222), or prognosis in grade IIIa patients receiving triptolide alone or triptolide and prednisone (χ(2) = 1.207, P = 0.272) and grade IIIb patients (χ(2) = 1.158, P = 0.282). No significant difference in clinical manifestations and long-term prognosis of our HSPN patients with grade IIIa or grade IIIb were found, implying that our patients with International Study and Kidney Disease in Children (ISKDC) grade IIIb were not the most severe cases of HSPN. Our results may also suggest that treatment with steroid may not alter the clinical outcome of such grade IIIa or IIIb patients.

Aberrant glycosylation of IgA1 is inherited in both pediatric IgA nephropathy and Henoch–Schönlein purpura nephritis

Serum galactose-deficient immunoglobulin A1 (Gd-IgA1) is an inherited risk factor for adult IgA nephropathy (IgAN). In this paper, we determined the heritability of serum Gd-IgA1 levels in children with IgAN and Henoch-Schönlein purpura nephritis (HSPN), two disorders with clinical phenotypes sharing common pathogenic mechanisms. Serum Gd-IgA1 concentrations were quantified using a Helix aspersa-lectin-based enzyme-linked immunosorbent assay. As a group, 34 children with either disorder (20 with HSPN and 14 with IgAN) had significantly higher Gd-IgA1 levels compared with 51 age- and ethnicity-matched pediatric controls. Serum levels of Gd-IgA1 were also elevated in a large fraction of 54 first-degree relatives of pediatric IgAN and HSPN patients compared with 141 unrelated healthy adult controls. A unilineal transmission of the trait was found in 17, bilineal transmission in 1, and sporadic occurrence in 5 of 23 families when both parents and the patient were analyzed. There was a significant age-, gender-, and household-adjusted heritability of serum galactose-deficient IgA1 estimated at 76% in pediatric IgAN and at 64% in HSPN patients. Thus, serum galactose-deficient IgA1 levels are highly inherited in pediatric patients with IgAN and HSPN, providing support for another shared pathogenic link between these disorders.

Henoch-Schönlein purpura nephritis with nephrotic state in children: predictors of poor outcomes

Nephritis develops in 18-81% of Henoch-Schönlein purpura patients, and the long-term outcomes of this nephritis show great variation. A nephrotic state at disease onset has been proposed as a predictor of poor renal outcomes. We studied 42 children with Henoch-Schönlein purpura nephritis (HSPN) who presented with a nephrotic state during the early phase of the disease. The median age of the patients at the time of diagnosis was 7.4years. The median follow-up period was 6.2years. Twenty-five children (60%) made a complete recovery; nine (21%) progressed to end-stage renal disease. Multivariate logistic regression analyses revealed that the nephrotic state lasting for more than 3months had a significant effect on renal outcomes (odds ratio 11.6; 95% confidential interval, 1.16-348.4; p = 0.03), whereas initial renal insufficiency, renal pathological findings, age at onset, and types of treatment did not. These findings indicate that clinical presentation, particularly duration of the nephrotic state, is related to long-term outcomes in HSPN patients with nephrosis. Our results also indicate that the therapeutic options for HSPN patients with a nephrotic state should be based on the clinical presentation rather than on the initial pathological findings alone.

Immune complexes in acute adult-onset Henoch-Schonlein nephritis

Adult-onset Henoch-Schönlein purpura nephritis (HSPN) and primary IgA (IgAN) nephropathy have been considered indistinguishable immunohistopathologically and are often considered as two extremes of one disease entity. We postulate that adult-onset Henoch-Schönlein can be distinguished histologically from primary IgAN and that both diseases differ in their immunopathological mechanisms. Twenty consecutive patients with adult-onset HSPN were studied. Serum was analysed for circulating IgA immune complexes; renal biopsies were analysed by light and electron microscopy (EM). As disease controls, 40 IgAN patients were studied. Intracapillary leukocyte margination was seen in 15 of the 20 patients and cellular crescent formation in all renal biopsies of the HSPN patients. IgAN biopsies showed a few small crescents without intracapillary leukocytes. In 16 HSPN patients, EM was performed and in 10, no dense deposits were found. In all biopsies of IgAN patients, typical 'humps' were found. In 6 of 9 analysed HSPN patients, intermediate to large circulating immune complexes were found, whereas in 4 of 28 analysed patients with primary IgAN small circulating immune complexes were found. We consider adult-onset HSPN distinguishable in histology and ultrastructure from primary IgAN. We believe adult-onset Henoch-Schönlein to be a circulating immune complex disease.

A clinical and pathological analysis in children with henoch-schonlein purpura nephritis

Objective To study the clinicopathology characteristics the clinical and pathological characteristics inchildren with henoch-schonlein purpura nephritis(HSPN). Methods The clinical,immunofluorescence and histopathologic features of 16 cases of HSPN were retrospectively studied. Results Among the 16 patients, 13 patients exhibited hematuria ,4 cases with proteinunia. Immunofluorescence study showed that 12 cases expressed IgA,7 cases expressed IgG,5 cases expressed C3. Grade Ⅱ had 62. 5% ,and grade Ⅲ had 37. 5%.Conclusion Renal glomerular lesion is a quite common finding in children with HSPN, and Grade Ⅱ and Ⅲ of pathological classification have been seen in the majority of HSPN patients. Key words: Nephritis; Purpura; Schoenlein-henoc; Children; Clinaic; Pathology

TLR-2 Arg753Gln, TLR-4 Asp299Gly, and TLR-4 Thr399Ile polymorphisms in Henoch Schonlein purpura with and without renal involvement

Infections may trigger or aggravate glomerulonephritidis and renal vasculitis like Henoch Schonlein purpura (HSP). HSP is seen more frequently in patients with familial Mediterranean fever in which TLR-2 Arg753Gln polymorphism frequency is increased. Although renal involvement is the most important factor affecting the prognosis in HSP, it is not known which patients will have renal disease or why some patients have severe renal involvement while some others have mild renal disease. We investigated the role of TLR-2 and TLR-4 polymorphisms on the incidence and severity of renal involvement in HSP patients. We studied HSP patients with and without nephritis (n = 15 for each group) and healthy controls (n = 100). TLR-2 Arg753Gln and TLR-4 Asp299Gly/Thr399Ile polymorphisms were analyzed with polymerase chain reaction-restriction fragment length polymorphism method. The frequency of TLR-2 Arg753Gln, TLR-4 Asp299Gly, and Thr399Ile polymorphisms in healthy controls were 1, 3, and 2%, respectively. The frequencies of these polymorphisms were not different in HSP patients with or without nephritis compared to healthy controls. TLR-2 Arg753Gln, TLR-4 Asp299Gly, and Thr399Ile polymorphisms are not increased in HSP or HSP nephritis patients.

Renal expression of alpha-smooth muscle actin and c-Met in children with Henoch–Schönlein purpura nephritis

Alpha-smooth muscle actin (alpha-SMA) is the actin isoform that predominates within vascular smooth-muscle cells and plays an important role in fibrogenesis. On the other hand, c-Met is the receptor for hepatocyte growth factor (HGF), which plays a role in protection from injury and has anti-fibrogenetic effects. To clarify whether alpha-SMA and HGF are associated with the progression of renal injury in Henoch-Schönlein purpura nephritis (HSPN), we evaluated the renal expression of alpha-SMA and c-Met in HSPN patients. Patients were divided into three groups. Group 1 consisted of eight patients (male:female 4:4) with stage II or less in the classification of the International Study of Kidney Disease in Children (ISKDC), Group 2 consisted of 20 patients (male:female 11:9) with ISKDC stage III or greater and a good prognosis, and group 3 consisted of seven patients (male:female 3:4) with ISKDC stage III or greater and poor prognosis. Renal biopsy findings, including c-Met and alpha-SMA staining, were investigated for each group. At first biopsy, the mean scores for renal alpha-SMA and glomerular c-Met in groups 2 and 3 were higher than those in group 1, while mean scores for neither renal alpha-SMA nor glomerular c-Met differed between groups 2 and 3. At second biopsy, the mean scores for renal alpha-SMA staining in group 3 were higher than those in group 2, and mean score for glomerular c-Met staining in group 3 was lower than that in group 2. In groups 2 and 3, the mean scores for glomerular and interstitial alpha-SMA staining at first biopsy were correlated with the chronicity index (CI) at second biopsy, but the mean score for glomerular c-Met staining at first biopsy correlated with neither the activity index (AI) nor CI in the first or second biopsies in all groups. Our findings suggest that the expression of renal alpha-SMA may be associated with progression of renal injury in HSPN.