Henoch-Schönlein Purpura Nephritis Research Articles

Serum-Urine Matched Metabolomics for Predicting Progression of Henoch-Schonlein Purpura Nephritis.

Henoch-Schonlein purpura nephritis (HSPN) is a common glomerulonephritis secondary to Henoch-Schonlein purpura (HSP) that affects systemic metabolism. Currently, there is a rarity of biomarkers to predict the progression of HSPN. This work sought to screen metabolic markers to predict the progression of HSPN via serum-urine matched metabolomics. A total of 90 HSPN patients were enrolled, including 46 HSPN (+) patients with severe kidney damage (persistent proteinuria >0.3 g/day) and 44 HSPN (–) patients without obvious symptoms (proteinuria < 0.3 g/day). Untargeted metabolomics was determined by liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-Q/TOF-MS). A total of 38 and 50 differential metabolites were, respectively, identified in serum and urine from the comparison between HSPN (+) and HSPN (–) patients. Altered metabolic pathways in HSPN (+) mainly included glycerophospholipid metabolism, pyruvate metabolism, and citrate cycle. A panel of choline and cis-vaccenic acid gave areas under the curve of 92.69% in serum and 72.43% in urine for differential diagnosis between HSPN (+) and HSPN (–). In addition, the two metabolites showed a significant association with clinical indices of HSPN. These results suggest that serum-urine matched metabolomics comprehensively characterized the metabolic differences between HSPN (+) and HSPN (–), and choline and cis-vaccenic acid could serve as biomarkers to predict HSPN progression.

Predictability of the Oxford classification of IgA nephropathy in Henoch-Schonlein purpura nephritis.

Whether the Oxford classification of immunoglobulin A nephropathy can be utilized to predict the adverse renal outcome of Henoch-Schonlein purpura nephritis (HSPN) has been long-debated. We, therefore, performed a meta-analysis to evaluate the prognostic value of Oxford classification lesions in HSPN. We systematically searched Medline, EMBASE, Web of Science, and the Cochrane Library for articles published from January 1970 to August 2020. Cohort and case-control studies investigating the correlation between the Oxford classification and renal outcome were included, the quality of which was assessed by the Newcastle-Ottawa scale criteria. The pooled odds ratios (ORs) with their 95% confidence intervals (CIs) were calculated with a random-effects model or a fixed-effects model depending on the heterogeneity. A total of 485 papers were reviewed and eventually 9 comparisons were included, providing data of 1688 patients with HSPN. ORs for adverse renal events were 2.83 (95% CI 1.84-4.35; P < 0.001), 1.96 (95% CI 1.28-2.98; P < 0.05), and 5.45 (95% CI, 3.15-9.45; P < 0.001) for patients with lesions of endocapillary hypercellularity (E), segmental sclerosis (S), and tubular atrophy /interstitial fibrosis (T), respectively, without significant heterogeneity (E: I2 = 0.0%; P = 0.498; S: I2 = 22.4%; P = 0.258; T: I2 = 33.6%; P = 0.171). Subgroup analysis adjusted for age also supported the results that E, S, and T lesions could serve as poor predictors (P < 0.05). Additionally, crescents (C) were strongly associated with renal outcome (OR 2.22; 95% CI 1.62-3.04; P < 0.001), with moderate heterogeneity (I2 = 49.3%; P = 0.066). However, it should be noted that it is not the presence but the proportions of crescent lesions that were related to the high risk of progression to adverse renal events, because the predictability of lower rates of crescent (C1, with crescents > 0 and ≤ 25%) was uncertain (OR 2.21; 95% CI 0.75-6.51; P > 0.05). Although the pooled OR revealed that lesions of mesangial hypercellularity (M) were correlated with poor renal prognosis (OR 2.41; 95% CI 1.07-5.43; P < 0.05), subgroup analysis separating children from adults indicated that there seemed to be no significant difference. Oxford classification, especially for E, S, T, and C, might be recommended for patients with HSPN, regardless of children and adults.

Using MEST-C Scores and the International Study of Kidney Disease in Children Classification to Predict Outcomes of Henoch-Schönlein Purpura Nephritis in Children.

Introduction: Henoch–Schönlein purpura nephritis (HSPN) and IgA nephropathy (IgAN) bear similarities in some aspects. The histological classification of HSPN was built on the International Study of Kidney Disease in Children (ISKDC) criteria, while IgAN was established on the 2016 Oxford classification (MEST-C scores). The purpose of this paper was to discuss the predictive value of the ISKDC classification and MEST-C scores in children with HSPN.Methods: We performed a retrospective study of 877 children with HSPN in a single center between 2001 and 2019. The primary outcome was defined as chronic kidney disease—estimated glomerular filtration rate (eGFR) <90 ml/min/1.73 m2.Results: During the follow-up period of 23.3 (10.9–47.9) months, 51 (5.8%) patients reached the primary outcome. As revealed in a Kaplan–Meier plot, segmental glomerulosclerosis (S) (P < 0.001) and tubular atrophy/interstitial fibrosis (T) (P < 0.001) significantly predict poor renal outcome. Other Oxford lesions and the ISKDC classification, however, did not show a significant difference in a worse outcome. In a multivariate Cox model adjusted for pathological and clinical factors, eGFR [hazard ratio (HR) = 2.831, 95% confidence interval (95% CI) = 1.359–5.896], S lesion (HR = 3.936, 95% CI = 2.078–7.457), and T lesion (HR = 4.002, 95% CI = 1.733–9.242) were independent risk factors for the renal outcome.Conclusion: This series constitutes the largest series reported so far in the literature of such patients. According to our findings, S and T of the Oxford classification, which are ignored by the ISKDC classification, could be applied to predict the renal prognosis of children with HSPN.

Efficacy and safety of mycophenolate mofetil versus cyclophosphamide in the treatment of Henoch-Schönlein purpura nephritis with nephrotic-range proteinuria in children: a prospective randomized controlled trial

Objective To study the efficacy and safety of mycophenolate mofetil (MMF) versus cyclophosphamide (CTX) in the treatment of children with Henoch-Schonlein purpura nephritis (HSPN) and nephrotic-range proteinuria. Methods A prospective clinical trial was conducted in 68 pediatric patients who were admitted to the Department of Nephrology, Children's Hospital Affiliated to Capital Institute of Pediatrics and who were diagnosed with HSPN and nephrotic-range proteinuria from August 2016 to November 2019. The patients were randomly divided into two groups:MMF treatment (n=33) and CTX treatment (n=35). The two groups were compared in terms of complete remission rate, response rate (complete remission + partial remission), urinary protein clearance time, and adverse events. Results At months 3, 6, and 12 of treatment, there was no significant difference in the complete remission rate and the response rate between the MMF treament and CTX treatment groups (P > 0.05). There was also no significant difference between the two groups in the urinary protein clearance time and the incidence rate of adverse events (P > 0.05). Conclusions MMF and CTX have similar efficacy and safety in the treatment of HSPN children with nephrotic-range proteinuria.

Clinical effect and mechanism of total glucosides of paeony in the adjuvant therapy for children with Henoch-Schönlein purpura nephritis: a prospective randomized controlled study

OBJECTIVE To study the clinical effect and mechanism of total glucosides of paeony (TGP) in the adjuvant therapy for children with Henoch-Schonlein purpura nephritis (HSPN). METHODS Sixty-four HSPN children with moderate proteinuria were divided into a TGP treatment group (n=34) and a routine treatment group (n=30) using a random number table. Thirty healthy children who underwent physical examination were enrolled as the healthy control group. The children in the routine treatment group were given conventional treatment alone, and those in the observation group were given TGP in addition to the conventional treatment. The two groups were compared in the clinical outcome after 4 weeks of treatment. The proportion of follicular helper T (Tfh) cells in peripheral blood and the plasma levels of interleukin-21 (IL-21) and interleukin-4 (IL-4) were measured in the healthy control group and the two HSPN groups. The changes in serum cystatin C (CysC) level and urinary alpha 1-microglobulin (A1M) concentration were compared before and after treatment in the two HSPN groups. RESULTS Compared with the healthy children before treatment, the children with HSPN had higher proportion of Tfh cells and expression levels of IL-21 and IL-4 (P < 0.01). The TGP treatment group had a higher overall response rate to treatment than the routine treatment group (94% vs 67%, P < 0.05). After treatment, both groups had reductions in the proportion of Tfh cells in peripheral blood, the expression levels of IL-21, IL-4, serum CysC, and urinary A1M concentration. The TGP treatment group had greater reductions in these indices than the routine treatment group (P < 0.01). CONCLUSIONS TGP has a marked clinical effect in the treatment of HSPN and can reduce the inflammatory response of the kidney and exert a protective effect on the kidney by inhibiting the proliferation of Tfh cells and downregulating the expression of IL-21 and IL-4 in plasma.

Delayed Presentation with Henoch–Schönlein Purpura in a Patient with Immunoglobulin a Nephropathy

Henoch–Schönlein purpura (HSP) nephritis (HSPN) and immunoglobulin A (IgA) nephropathy (IgAN) are related conditions that may be encountered sequentially in the same patient, are described in twins, and have common biological and pathological basis. The clinical features as well as the spectrum of severity at presentation vary significantly among patients. Here, we report a girl who first presented with acute glomerulonephritis and biopsy evidence of acute diffuse proliferative IgA nephritis with crescents, and 5 years later, she developed HSP and proteinuria. Such delayed appearance of cutaneous manifestations after initial renal involvement is unusual, though reported previously. This presentation stresses the importance of long-term follow-up of patients with HSPN and primary IgAN.

Relevance of glomerular C4d deposition in pediatric patients with Henoch-Schönlein Purpura compared to IgA nephritis

Introduction: IgA nephropathy (IgAN) is the most common primary glomerulonephritis (GN) in western countries and Henoch-Schonlein purpura nephritis (HSPN) is the most common form of vasculitis in childhood. Renal biopsy findings in both nephropathies are often similar and are characterized by mesangioproliferative GN with mesangial or mesangiocapillary IgA and C3c deposits. Objectives: The aim of this study was to investigate the significance of glomerular C4d-deposition as a discriminating factor between pediatric HSPN and IgAN. Patients and Methods: We retrospectively analyzed patient records and renal biopsies from 53 pediatric patients from one single center with a median age of 10.5 years (range 2.3-18 years). Twenty-two patients suffered from IgAN and 31 from HSPN. Work-up of all renal biopsies was performed using standard protocols including immunohistochemistry for C4d. Results: Pediatric IgAN patients presented significantly more often with gross hematuria, higher serum creatinine, lower glomerular filtration rate, lower serum C3 and proteinuria and on histology less endocapillary hypercellularity compared to HSPN patients. However, the rate of glomerular C4d-positivity was not different between IgAN (36%) and HSPN (42%). Comparing all cases with positive versus negative glomerular C4d-staining, pediatric patients with glomerular C4d-positivity showed significantly lesser gross hematuria and received significantly more often cyclophosphamide. This was in line with a tendency towards more proteinuria, hypertension and renal insufficiency at last follow-up in C4d-positive compared to C4d-negative patients. Conclusion: In conclusion, in our monocentric study glomerular C4d does not differ between pediatric HSPN and IgAN, but was associated with a tendency to a more severe course of the disease that needs to be confirmed in larger multicentric studies.

Immunohistochemical detection of citrullinated histone H3-positive neutrophils is useful for identifying active glomerular and interstitial lesions in antineutrophil cytoplasmic antibody-associated vasculitis.

Activated neutrophils release neutrophil extracellular traps (NETs), resulting in a form of cell death called NETosis. NET formation is reportedly involved in the onset of systemic lupus erythematosus and antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Citrullination of histones is a key step in NET formation, and the presence of citrullinated histones in neutrophils may be associated with disease induction and activity. The aim of this study was to investigate the relationship between infiltrating citrullinated histone H3 (H3Cit)-positive neutrophils and disease specificity and activity in various glomerulonephritides. We selected 32 kidney biopsies with glomerulonephritides, including AAV, lupus nephritis (LN), Henoch-Schönlein purpura nephritis (HSPN), and poststreptococcal acute glomerulonephritis (PSAGN). We examined the presence of H3Cit in infiltrating neutrophils and their association with necrotising, crescentic lesions and tubulointerstitial lesions. In PSAGN and HSPN, we found many myeloperoxidase (MPO)+ neutrophils in glomeruli; however, only a few were H3Cit+. In LN, MPO+ neutrophils mainly existed in the margins of glomerular tufts forming wire-loop lesions, and some of these were noted to be H3Cit+ neutrophils. In contrast, we found a significantly higher frequency of H3Cit+ neutrophils, despite the small number of MPO+ neutrophils, in microscopic polyangiitis in AAV. In particular, H3Cit+ neutrophils were prominent in necrotising lesions along the glomerular capillaries. Moreover, we also found H3Cit+ neutrophils in the interstitium, with marked peritubular capillaritis in AAV. H3Cit immunostaining is a useful tool for identifying activated neutrophils. The frequency of H3Cit+ neutrophils is not only a disease-specific marker but also a potential marker for disease activity in AAV.

Positive effect of individualized grading nursing on blood coagulation function in children with henoch schonlein purpura nephritis.

Positive effect of individualized grading nursing on blood coagulation function in children with henoch schonlein purpura nephritis.

Effect observation of individualized graded nursing on blood coagulation function in children with henoch schonlein purpura nephritis.

Effect observation of individualized graded nursing on blood coagulation function in children with henoch schonlein purpura nephritis.

Value of electron microscopy in the pathological diagnosis of native kidney biopsies in children.

Pediatric native kidney diseases are common worldwide. The pathological diagnosis of kidney lesions is crucial for clinical treatment and prognosis. The aim of the current study was therefore to evaluate the value of electron microscopy (EM) to the final diagnosis of native kidney biopsies in children. A retrospective evaluation of 855 pediatric kidney biopsies obtained from the Department of Pediatrics in Peking University First Hospital between November 2010 and December 2017 was performed to assess the contribution of EM to the final diagnosis. The role of EM in the final diagnosis was determined to be crucial in 300 cases (35.1%), important in 280 cases (32.7%), and auxiliary in 275 cases (32.2%). EM is considered most valuable in a large percentage of glomerular diseases, mainly including minimal change disease, early-stage membranous nephropathy, postinfectious glomerulonephritis, Alport syndrome, thin basement membrane nephropathy, and thrombotic microangiopathy. EM also provided helpful diagnostic information in cases of focal segmental glomerulosclerosis, lupus nephritis, IgA nephropathy, and IgA vasculitis (Henoch-Schonlein purpura nephritis). Additionally, EM was crucial in 90.0% of cases of subtle pathological changes observed with light microscopy (LM) and immunofluorescence (IF) and in 69.3% of the IF-negative specimens. Patients with nephrotic syndrome or hematuria also benefit from ultrastructural examination. The present study demonstrated the crucial or important role of EM in the diagnosis of a majority of native kidney biopsies in children. The application of EM should be integrated together with LM and IF as a routine method of assessing pediatric kidney specimens. Graphical abstract.

An Integrated Transcriptomic and Proteomic Analysis Identifies Significant Novel Pathways for Henoch-Schönlein Purpura Nephritis Progression.

Background Although Henoch-Schönlein purpura nephritis (HSPN) is characterized by glomerular deposition of aberrantly glycosylated immunoglobulin A1 (IgA1), the underlying mechanism of HSPN progression has not yet been completely elucidated. In this study, we integrated transcriptomic and proteomic analyses to explore the underlying mechanism of HSPN progression. Methods RNA sequencing and tandem mass tag- (TMT-) based quantitative proteomics were used to gain serum transcriptomic and proteomic profiles of patients with different types of HSPN (3 × type 1, 3 × type 2, and 3 × type 3). Student's t-tests were performed to obtain the significance of the differential gene expression. The clusterProfiler package was used to conduct the functional annotation of the DEGs for both Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways. Results A total of 2315 mRNAs and 30 proteins were differentially expressed between the different types of HSPN. 58 mRNAs and one protein changed continuously during HSPN development and are potential biomarkers for HSPN progression. The validation cohort (another 9 patients) confirmed the high-throughput results of the transcriptomic and proteomic analyses. A total of 385 significant pathways were related to HSPN progression, and four of them were closely related to clinical biochemical indicators and may play an important role in the progression of HSPN. Those pathways reveal that HSPN progression may be related to the inhibition of inflammation, promotion of apoptosis, and repair of renal injury. Conclusions Four pathways were found to be closely related to HSPN progression, and it seems that HSPN progression is mainly due to the inhibition of inflammation, promotion of apoptosis, and repair of renal injury.

Apoptosis inhibitor of macrophage as a biomarker for disease activity in Japanese children with IgA nephropathy and Henoch-Schönlein purpura nephritis.

To evaluate the apoptosis inhibitor of macrophage (AIM) deposition patterns on the kidneys of children with IgA nephropathy (IgAN) and Henoch-Schönlein purpura nephritis (HSPN) and to investigate the clinical usefulness of serum and/or urinary AIM levels as biomarkers for the disease activity. Immunohistochemical study was performed in the kidneys of 37 patients with IgAN and 10 patients with HSPN. Serum and urinary AIM levels in the patients and 20 healthy controls (HCs) were quantified by enzyme-linked immunosorbent assay. The results were compared with clinical features. In patients with IgAN and HSPN, AIM expression was observed in various areas, including the glomerular mesangial and capillary areas, the proximal and distal tubular epithelial cells, and on infiltrating macrophages in the glomeruli and interstitial areas. Serum and urinary AIM levels were significantly elevated in these patients compared with the HCs. Urinary AIM levels were positively correlated with the histological severity and degree of proteinuria and hematuria as well as urinary β2 microglobulin and urinary N-acetyl-β-D-glucosaminidase levels. AIM plays an important role in the pathogenesis of IgAN and HSPN. Urinary AIM levels can potentially reflect active renal inflammation in these diseases and may represent a useful biomarker for disease activity. Urinary AIM levels may represent a useful biomarker for disease activity of IgAN and HSPN. AIM expression was observed in the glomeruli, tubular epithelial cells, and infiltrating macrophages in glomeruli and interstitial area. U-AIM/Cr were significantly correlated not only with proteinuria, hematuria, and u-β2MG and u-NAG levels but also with the activity index of histological findings in kidney biopsy specimens. Our results can emphasize the important role of AIM in the pathogenesis of IgAN and HSPN.

Activation of Complement System in Henoch-Schönlein Purpura Nephritis

Introduction: We studied the association between Henoch-Schönlein purpura nephritis (HSPN) and complement system activation. Methods: We retrospectively reviewed the pathologic findings and medical records of 35 children and 12 adults with HSPN and compared the differences according to C4d positivity in three groups consisting of total 47 patients, 35 pediatric and 12 adult patients, respectively. C4d staining of renal biopsy was additionally performed at the time of diagnosis or retrospectively using archival biopsy material. Results: The overall rate of C4d positivity was 53.2%: 20 (57.1%) of the 35 children and five (41.7%) of the 12 adults. Among the groups there was no significant difference in the severity of proteinuria, renal function, presence of crescents or mesangial proliferation stratified by C4d positivity, unlike IgA nephropathy. Conclusions: We suggest that the activation of complement system is not correlated with the clinical or pathological severity of HSPN.

Comparison of clinicopathological features and prognosis between IgA nephropathy and purpura nephritis in adults with diffuse endocapillary proliferation: a single-center cohort study.

Clinical manifestations and histological lesions of IgA nephropathy and Henoch-Schönlein purpura nephritis (HSPN) are different, but related, and are also correlated with the renal outcomes. This study aimed to compare the features of immunoglobulin A nephropathy (IgAN) and HSPN in adult patients with diffuse endocapillary proliferation (DEP) lesions aiming to clarify the differences and relationships in the clinicopathological findings and outcome. Twelve patients with DEP-IgAN and 10 patients with DEP-HSPN were enrolled. Twenty four patients with IgAN (NDEP-IgAN) and matched 20 patients with HSPN (NDEP-HSPN) were enrolled at the same ratio (1:2). The clinicopathological features, clinical efficacy, and renal outcomes were analyzed in the four groups. DEP patients with IgAN or HSPN had worse clinical manifestations (more severe proteinuria, lower serum ALB, higher incidence of gross hematuria). The proteinuria in the DEP-HSPN group was more severe than in the DEP-IgAN group. There was no significant difference in the serum creatinine among four groups. The incidence of endothelial swelling was significantly higher in the DEP-HSPN group than in the NDEP-HSPN group and DEP-IgAN group. The S1 score of Oxford classification was more common in the DEP-IgAN group than in the DEP-HSPN. None in the DEP-IgAN group reached endpoint events during the follow-up period, while the renal outcomes were significantly poorer in the DEP-HSPN group than in the DEP-IgAN and NDEP-HSPN groups. No significant difference was observed in the cumulative renal survival among four groups (χ 2 =7.264, P=0.064), but patients in the DEP-HSPN group had markedly lower renal cumulative survival rate as compared to the NDEP-HSPN group (χ 2 =4.875, P=0.027). The DEP is significantly associated with more severe proteinuria and hematuria regardless the IgAN and HSPN. Among DEP patients, patients with HSPN have poor therapeutic efficacy and renal outcomes, even under active immunosuppressive therapy, as compared to those with IgAN.

Expression and significance of follicular helper T cells and galactose-deficient IgA1 in children with Henoch-Schönlein purpura

To study the role of follicular helper T (Tfh) cells and galactose-deficient IgA1 (Gd-IgA1) in the pathogenesis of childhood Henoch-Schönlein purpura (HSP) and the correlation between them. A total of 36 children with newly-diagnosed HSP were enrolled. They were divided into two groups: HSP nephritis (HSPN) group with 11 children and non-HSPN group with 25 children according to the presence or absence of HSPN. Another 15 children who underwent physical examination at the outpatient service were enrolled as the healthy control group. Flow cytometry was used to measure the proportion of Tfh cells (CD4+CXCR5+ICOS+) in peripheral blood. ELISA was used to measure the levels of interleukin-21 (IL-21) and interleukin-6 (IL-6) in peripheral blood and the serum levels of IgA1 and Gd-IgA1. A Pearson correlation analysis was used to investigate the correlation of serum Gd-IgA1 concentration with Tfh cells and related factors expression in the children with HSP. Both the HSPN and non-HSPN groups had significantly higher proportion of Tfh cells and expression levels of IL-21 and IL-6 in peripheral blood than the healthy control group (P<0.05). The HSPN group had significant increases in the above indices compared with the non-HSPN group (P<0.05). Both the HSPN and non-HSPN groups had significantly higher serum levels of IgA1 and Gd-IgA1 than the healthy control group (P<0.05). The HSPN group had significantly higher serum levels of IgA1 and Gd-IgA1 than the non-HSPN group (P<0.05). In the children with HSP, serum Gd-IgA1 level was positively correlated with Tfh cells proportion and IL-21 and IL-6 levels (P<0.05). Tfh cells and related cytokines and serum Gd-IgA1 are involved in the development of HSP/HSPN. Tfh cells may mediate the increased production of Gd-IgA1.

The Role of MIF-173G/C Gene Polymorphism in the Susceptibility of Autoimmune Diseases.

Some certain genetic polymorphisms have been considered to implicate in the pathogenesis and progression of autoimmune diseases and may predispose to an early stage of general autoimmune susceptibility. Recent studies have been conducted to investigate the association between macrophage migration inhibitory factor- (MIF-) 173G/C gene polymorphism and autoimmune diseases; however, the results were not exactly identical. In the present study, a systematic review and meta-analysis of case-control studies was performed to estimate the relationship. A comprehensive search of PubMed, Ebsco, EMbase, WanFang databases and CNKI was done. Odds ratio (ORs) and corresponding 95% confidence intervals (CIs) were combined to pool the effect size. The publication bias was examined by Begg's funnel plots and Egger's test. RevMan 5.3 and STATA 12.0 software were used for statistical processing. 23 papers were included, and the results revealed that MIF-173G/C was significantly associated with an increased risk of autoimmune diseases in five genetic models (recessive genetic model: OR = 1.95, 95% CI: 1.52-2.50; dominant genetic model: OR = 1.35, 95% CI: 1.24-1.46; allele model: OR = 1.32, 95% CI: 1.23-1.41; homozygote model: OR = 1.92, 95% CI: 1.57-2.35; heterozygote model: OR = 4.92, 95% CI: 4.03-6.02), whether in Asia, Europe, or North America. Furthermore, subgroup analysis showed an increasing risk in rheumatoid arthritis (RA), ulcerative colitis (UC), Crohn's disease (CD), atopic dermatitis (AD), Henoch-Schonlein purpura (HSP), and Henoch-Schonlein purpura nephritis (HSPN), but it was not related to the susceptibility of autoimmune hepatitis (AIH). Therefore, it could be considered that MIF-173G/C polymorphism could increase the susceptibility of autoimmune diseases, while there may be the discrepancy of disease entity.

A cross-sectional analysis of clinicopathologic similarities and differences between Henoch-Schönlein purpura nephritis and IgA nephropathy.

Recent studies noted that Henoch-Schönlein purpura nephritis (HSPN) and IgA nephropathy (IgAN) share the feature of galactose-deficient IgA1 (Gd-IgA1)-oriented pathogenesis, although there are distinct clinical differences. We aimed to clarify the clinicopathologic differences between these 2 diseases. We cross-sectionally analyzed adult patients with HSPN (n = 24) or IgAN (n = 56) who underwent renal biopsy (RB) between 2008 and 2018 at Showa University Hospital. Serum Gd-IgA1 (s-Gd-IgA1) levels at the time of RB were compared among study groups using enzyme-linked immunosorbent assay (ELISA) with anti-human Gd-IgA1-specific monoclonal antibody (KM55). We also immunohistochemically stained paraffin-embedded sections for glomerular Gd-IgA1 (g-Gd-IgA1)-deposition using KM55. Serum inflammatory cytokines were measured using ELISA. Glomerular endothelial injury with subendothelial IgA deposition was significant in patients with HSPN. Serum IL-8, MCP-1, TNF-α, and IL-6 levels were significantly higher in patients with HSPN than IgAN. Levels of s-Gd-IgA1 were comparable among patients with HSPN and IgAN, and a similar degree of g-Gd-IgA1-deposition was detected in both diseases. Furthermore, g-Gd-IgA1-deposition was evident in patients with histopathologically advanced HSPN or IgAN. In HSPN, significant positive correlations between s-Gd-IgA1 levels and crescent formation or IL-6 elevation were confirmed, and g-Gd-IgA1 intensity showed a significant positive correlation with MCP-1 and a tendency to positively correlate with IL-8. Meanwhile, patients with IgAN showed no correlation between inflammatory cytokines and both-Gd-IgA1. Moreover, most g-Gd-IgA1-positive areas were not double stained with CD31 in HSPN. Although assessing both-Gd-IgA1 alone was insufficient to distinguish between HSPN and IgAN, patients with HSPN showed considerable glomerular capillaritis with subendothelial IgA deposition and significant elevation of serum inflammatory cytokines. Furthermore, such glomerular subendothelial IgA deposition might not contain Gd-IgA1, and factors associated with Gd-IgA1 were inconsistent among these 2 diseases. Thus, developmental mechanisms for IgAN might not apply to HSPN completely, and these 2 diseases still have different aspects.

Progress in research on the effects of high mobility group box 1 in pediatric rheumatic diseases

High mobility group box 1 is a kind of non-histone protein which expressed in the nucleus of eukaryotic cells.Which can promote inflammatory reaction and participate in the positive feedback loop of the production of cytokines after translocated outside the cells.As a result, it′s closely related to the pathogenesis of various autoimmune and inflammatory diseases.Recent studies have revealed that high mobility group box 1 may serve as a serum marker of Henoch-Schonlein purpura nephritis and lupus nephritis, and a predicator of the prognosis of juvenile idiopathic arthritis and intravenous immunoglobulin resistance in Kawasaki disease. Key words: High mobility group box 1; Rheumatic disease; Child

SAT-412 TEN-YEAR TRENDS IN DIAGNOSIS OF KIDNEY DISEASES IN JAPAN -THE JAPAN KIDENY DISEASE REGISTRY/JAPAN RENAL BIOPSY REGISTRY (J-KDR/J-RBR)

The incidence and age distribution of pathological diagnosis of kidney diseases vary throughout the world by race, ethnicity, environment and medical systems. Japanese Society of Nephrology (JSN) launched a nation-wide kidney disease registry, Japan kidney disease registry/Japan renal biopsy registry (J-KDR/J-RBR) in 2007. The aim of the present study was to clarify the ten-year trends of the pathological diagnosis of kidney disease among patients who underwent renal biopsy in Japan. Data were extracted from the database registered between July 2007 and June 2017. The number and rate of patients with various glomerular diseases including IgA nephropathy (IgAN), Henoch-Schönlein purpura nephritis (HSPN), and nephrotic syndrome (NS) were clarified and the trends were analyzed. The J-RBR is registered to the Clinical Trial Registry of UMIN (registered number UMIN000000618) and is available in Japanese and English. The data of cases (n=38, 318) registered in the J-RBR between July 2007 and June was extracted. The patients who underwent the first renal biopsy (n=20,139) were eligible for the first study. The number (the rates) of cases diagnosed with IgAN, HSPN, and NS were 6,322 (31%), 548 (2.7%), and 5,945 (30%), respectively. IgA vasculitis, including IgAN and HSPN, occupied 50% in 10 to 39 years old cases. The diagnosis of primary NS was made on 67% of total NS cases. The top pathological diagnosis of secondary NS was diabetic nephropathy, followed by lupus nephritis. Among primary NS, 44% was diagnosed with minimal change disease (MCD), 39% with membranous nephropathy (MN), and 11% with focal segmental glomerulosclerosis (FSGS). Most of the MN patients were over 40 years old while MCD and FSGS distributed widely to all ages. Of note, the substantial number of patients diagnosed with MCNS was over 70 years old. In the next study, we extracted the patients over 20 years old (n=30,935). Of these, IgAN occupied 30%, and primary NS occupied 15%. We analyzed the trends of pathological diagnosis. The rate of IgAN slightly decreased from 31% in 2008 to 27% in 2017. The rate of MCNS among primary NS was 32% at 2008, which gradually increased to 37% in 2013, and 43% in 2017. The rate of MN showed the similar levels: 46% in 2008 and 45% in 2017. When we analyzed age distribution, the peak of MN was at 60ies in 2009, while the peak had moved to 70ties by 2017. The rate of MPGN among NS patients markedly decreased from 10% in 2008 to 2.8% in 2017. The rate of FSGS varied each year between 9 to 12%, showing no clear trends. The age distribution of total cases registered in J-RBR showed a single peak at early 60 ties in 2009, which moved to late 60ites in 2016, suggesting the good association with the rapidly aging population in Japan. Nation-wide renal biopsy registry revealed the change in incidence of type of glomerular diseases in Japan. IgAN was the most common pathological diagnosis occupying about 30% of entire renal biopsy cases. The data indicate that incidence of IgAN and MPGN decreased, and that of MCNS increased in the past ten years, while the rate of MN was constant. One of the reasons for these trends may be attributable to the rapid change in the age distribution in Japan.