ABSTRACT
IgA vasculitis is a common autoimmune disease mediated by IgA in childhood, which can involve many systems.Henoch-Sch?nlein purpura nephritis(HSPN)is one of the main complications.Both HSPN and IgA nephropathy(IgAN)are common glomerulonephritis in children, but the former is the most common secondary glomerulonephritis and the latter is one of the most persistent diseases in primary glomerulonephritis.There are differences in clinical phenotype and prognosis.This article reviews the relevant literature, and summarizes the similarities and differences in the pathogenesis of HSPN and IgAN, so as to better understand the two diseases.
ABSTRACT
IgA nephropathy (IgAN) is one of the common primary glomerulonephritis, which is also an important risk factor for end-stage renal disease. Kidney transplantation is the optimal treatment for end-stage renal disease induced by IgAN, whereas there is still a risk of recurrence of IgAN after kidney transplantation. At present, research progress upon IgAN recurrence after kidney transplantation is relatively lacking. The pathogenesis of IgAN recurrence remains elusive, and its pathological manifestations are not specific. The diagnosis of IgAN recurrence still depends on renal biopsy. Besides, no effective prevention and treatment are available for recurrent IgAN. In this article, research progress on IgAN recurrence after kidney transplantation was illustrated from the perspectives of pathogenesis, diagnosis, risk factors and treatment, aiming to provide reference for clinical prevention and treatment of IgAN recurrence after kidney transplantation and improve clinical prognosis of kidney transplant recipients.
ABSTRACT
ObjectiveThe effect of modified Shengjiangsan on immunoglobulin A （IgA） nephropathy was observed. The microRNA-148b （miRNA-148b）， interleukin 6 （IL-6）， core 1 beta 1，3-galactosyltransferase （C1GALT1）， molecular chaperone Cosmc （core1β3-Gal-T-specific molecular chaperone C1GALT1C1）， and galactose-deficient IgA1 （Gd-IGA1） in serum and kidney tissues of IgA nephropathy rats were detected to explore the underlying mechanism. The result is expected to lay a scientific basis for clinical application of modified Shengjiangsan in the treatment of IgA nephropathy. MethodA total of 42 SPF male SD rats were randomized into the normal group （8rats） and modeling group （34 rats） with the random number table method. After one week of adaptive feeding， rats for modeling were given bovine serum albumin （BSA， gavage）， lipopolysaccharide （LPS， injection into tail vein）， carbon tetrachloride （CCl4， subcutaneous injection）， and castor oil to induce IgA nephropathy. After modeling， two rats were randomly selected to test the modeling outcome. Then the model rats were classified into the model group， low-dose Chinese medicine group （modified Shengjiangsan，6.27 g·kg-1）， high-dose Chinese medicine group （modified Shengjiangsan，12.54 g·kg-1）， and benazepril group （10 mg·kg-1） with the random number table method， 8 in each group. The administration （gavage， once a day） lasted 4 weeks. The 24-h urinary total protein （24 h-UTP） was detected at the end of the 1st， 9th， and 13th week of the experiment. At the 14th week， after anesthesia， femoral artery blood was collected and centrifugated. The supernatant was collected to detect albumin （ALB）， aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， serum creatinine （SCr）， and blood urea nitrogen （BUN）. The expression levels of IL-6 and Gd-IGA1 were determined by enzyme-linked immunosorbent assay （ELISA）. Based on hematoxylin-eosin （HE）/Masson/periodic Schiff-methenamine silver （PASM） staining， the pathological changes of renal tissues were observed. Ultrastructural changes of glomeruli were observed by transmission electron microscopy. The expression of miRNA-148b， IL-6， C1GALT1， and C1GALT1C1 was detected by immunohistochemistry. The mesangial area of the glomeruli was observed by immunofluorescence. Real-time polymerase chain reaction （Real-time PCR） was employed to determine the mRNA levels of mirNA-148b， IL-6， C1GALT1， and C1GALT1C1， and Western blot was used to detect the protein levels of IL-6， C1GALT1， and C1GALT1C1. ResultCompared with normal group， the model group showed increase in the content of 24 h-UTP， SCr， ALT， IL-6， and GD-IGA1 （P<0.05）， decrease in ALB content （P<0.05）. Moreover， rats in the model group demonstrated hyperplasia of glomerular mesangial cells， thickening of mesangial area， podocyte foot process effacement， and a large number of granular IgA immune complex in the mesangial area. In addition， the model group showed increase in the expression of IL-6 in mesangial area and podocytes， decrease in the expression of C1GALT1 and C1GALT1C1 in mesangial area and podocytes， enhanced expression of IL-6 mRNA and miRNA-148b （P<0.01）， weakened expression of C1GALT1 mRNA and C1GALT1C1 mRNA （P<0.01）， rise of IL-6 protein expression （P<0.01）， and reduction in the protein expression of C1GALT1 and C1GALT1C1 （P<0.01）. Compared with the model group， modified Shengjiangsan decreased the content of 24 h-UTP， SCr， ALT， IL-6， and Gd-IGA1 （P<0.05） and increased the content of ALB （P<0.05， P<0.01）. Moreover， with the treatment of this Chinese medicine， the pathological damage was significantly alleviated and the deposition of IgA immune complex in basement membrane was reduced. The expression of IL-6 in the mesangial area and podocytes of rats was decreased， and the expression of C1GALT1 and C1GALT1C1 in the mesangial area and podocytes of rats was increased. Moreover， the expression of IL-6 mRNA and miRNA-148b was decreased （P<0.01）， and the expression of C1GALT1 mRNA and C1GALT1C1 mRNA was increased （P<0.01）. The protein expression of IL-6 was decreased （P<0.05， P<0.01）， and the protein expression of C1GALT1 and C1GALT1C1 was enhanced （P<0.05， P<0.01）. The Chinese medicine group showed obvious dose-effect trend. ConclusionModified Shengjiangsan may reduce the expression of miRNA-148b and IL-6 in serum and kidney tissue of IgA nephropathy rats， restore the expression of C1GALT1 and C1GALT1C1， and decrease the generation of Gd-IGA1， so as to reduce renal pathological damage and proteinuria， protect the kidney protection， and finally delay the disease progression. Moreover， the effect is enhanced with the rise of dose.
ABSTRACT
Objective:To investigate the role of follicular helper T(Tfh) cells and galactose deficiency IgA 1(Gd-IgA 1) in the children that were suffering from Henoch-Sch?nlein purpura(HSP) and Henoch-Sch?nlein purpura nephritis(HSPN)and the correlation between them. Methods:According to the presence or absence of renal injury, 62 children with HSP were divided into HSP group with 32 children and HSPN group with 30 children.Twenty children who underwent physical examination at outpatients were known as the healthy control group.Flow cytometry was used to measure the proportion of Tfh(CD4 + CXCR5 + PD-1 + ) in peripheral blood.Immunoturbidimetry and ELISA were used to measure the serum levels of IgA 1 and Gd-IgA 1 respectively. Results:(1) The proportion of Tfh cells in peripheral blood and the serum levels of Gd-IgA 1 in both HSP group and HSPN group had significantly increased than those in healthy control group( P<0.01). Compared result of the HSPN group with HSP group, the proportion of Tfh cells in peripheral blood and the serum levels of Gd-IgA 1 in HSPN group were higher than that in HSP group( P<0.05). (2) In the HSPN group, the proportion of peripheral blood Tfh cells and the serum levels of Gd-IgA 1 in group of renal pathology ≥ grade Ⅲ and heavy proteinuria were significantly elevated compared with group of renal pathology < grade Ⅲ and non-heavy proteinuria(<0.01). (3) In the healthy control group, the serum levels of Gd-IgA 1 was positively correlated with the proportion of Tfh cells in peripheral blood and the serum levels of Gd-IgA 1( P<0.05). Conversely, a non-positive correlation was shown in HSP and HSPN groups( P>0.05). Conclusion:The excessive activation of Tfh cells and the serum levels of Gd-IgA 1 may be one of the pathogenesis of HSP/HSPN, the degree of increment of the two factors may be related to the activity and severity of the disease.The mechanism of Tfh cells potentially leading to an increase of Gd-IgA 1 production requires further study.
ABSTRACT
OBJECTIVE: To investigate the value of serum galactose-deficient IgA1 in the diagnosis of IgA nephropathy and explore its relationship with the decline of renal function and pathological grade of renal biospy samples of the patients. METHODS: The serum samples were collected from, Shengjing Hospital of China Medical Unerversity from January 2016 to December 2017,which included 40 IgA nephropathy patients(group A), 20 other primary glomerulonephritis patients(group B) and 20 healthy persons(group C).Serum levels of GD-IgA1 were detected in all the samples.The 24-hour urinary protein and serum creatinine were measured in group A and B,the eGFR calculated. Recorded the pathological grade of renal biospy samples and Lee's classification. Study the value of serum Gd-IgA1 level in diagnosing IgA nephropathy by drawing ROC curve and calculating the area under the curve. RESULTS: The serum levels of GdIgA1 in IgA nephropathy patients were significantly higher than those in other types of primary glomerular diseases and healthy controls.The area under ROC curve was 0.886.When serum Gd-IgA1 level is higher than 662.5 U/ml, it suggested that people were more likely to have a IgA nephropathy.The level of serum Gd-IgA1 was related to the decline of renal function and pathological grade of renal biospy samples in patients with IgA nephropathy. CONCLUSION: Serum Gd-IgA1 levels may be helpful in the diagnosis of IgA nephropathy in patients who can not undergo renal pathological examination.
ABSTRACT
Henoch-Sch?nlein purpura ( HSP ) is a well-known systemic vasculitis disease mediated by IgA1 immune complex in children, and the pathogenesis remains unclear. Henoch-Sch?nlein purpura nephritis ( HSPN) is the most serious complication when the kidneys are damaged. It is also the key to determine the prog-nosis of the disease. Due to a combination of genetic,environmental,and infectious factors,IgA1 is abnormally glycosylated during the immune response. Galactose-deficient immunoglobulin A1(Gd-IgA1)is easy to self-ag-gregate and recognized by the antibody to form an immune complex deposited in the glomerular mesangial, which lead to kidney damage. This article reviews the progress of a series of pathogenic mechanisms of IgA1 glycosylation abnormality in HSPN.
ABSTRACT
In recent years,studies have shown that galactose - deficient IgA1(Gd - IgA1)antibodies are im-portant in the pathogenesis of IgA nephropathy(IgAN). Serum levels of Gd - IgA1 antibodies are associated with levels of proteinuria and renal histological grading. Measuring the antibodies has guidance value in the diagnosis of IgAN,for its sensitivity and specificity can be up to 88% - 89% and 89% - 92% respectively. In addition,the antibodies play an important role in clinical prognosis,and it may provide a new direction for treatment in IgAN. Now,its role in prognosis of IgAN was reviewed.
ABSTRACT
The immunopathogenesis of IgA vasculitis and IgA nephropathy both demonstrate IgA deposition,and abnormal glycosylation of IgAl molecule is their major pathogenesis.Therefore,it is clinically controversial that they are actually one disease.The present text will delineate their similarities and differences from aspects of epidemiology,clinic,pathology,mechanism and prognosis.
ABSTRACT
The research on the clinical characteristic and epidemiology in Henoch-Schonlein purpara of children indicates that genetic factors are closely connected with the disease and pathological process.In recent years,molecular biology studies show that C1 GALT1 gene,IL gene,vasomotor and endothelial function regulation genes,angiotensin-converting enzyme gene,angiotensinogen gene,MEFV gene and so on,which have aberrant IgAl giycosylation,are closely related with pathogenesis of Henoch-Schonlein purpura in children.The paper reviews the progress of genetic mechanism associated with Henoch-Schonlein purpura in recent years.
ABSTRACT
The T-cell immunoglobulin- and mucin-domain-containing molecules (Tim) have been implicated in the pathogenesis of immune diseases. In this study, we used quantitative realtime reverse transcription-polymerase chain reaction to examine the Tim-1 mRNA expression in peripheral blood mononuclear cells from Henoch-Schönlein purpura patients. The results showed that Tim-1 mRNA expression was significantly higher in patients, which was closely correlated with serum TNF-α, IL-4 levels, IgA1 levels.
ABSTRACT
IgA nephropathy is one of the most common glomerulonephritis in the world.Although the pathogenesis of IgA nephropathy is not clear yet, many studies have manifested that many factors such as environmental factors,genetic factors,and aberrantly glycosylated IgAlare involved in its pathogenesis. Currently, most studies focus on aberrantly glycosylated IgAl, lgA 1 circulating immune complexes depositing and abnormal IgAl removing.In addition, studies have found that ACE gene polymorphism especially DD genotype may be associated with the pathogenesis of IgA nephropathy.Furthermore, T lymphocytes, B lymphocytes,dendritic cells, transforming growth factor β1 and so on play an important role in the pathogenesis of lgA nephropathy.
ABSTRACT
Objective To examine the expression of IgA1 and B1a positive cells in palatine tonsils of IgA nephropathy (IgAN) patients, and to analyze the association between B1a cells and clinicopathological changes. Methods Eight patients diagnosed as IgAN by renal biopsy and 8 chronic tonsillitis patients without nephritis as control were enrolled in the study.Immunofluorescence and laser scanning confocal microscope (LSCM) were applied to observe the localization and quantitative calculation of Bla and IgA1 positive cells. Statistic analysis of the association of B1a cells with proteinuria and pathological Lee's grading was performed. Results Bla cells were mainly localized in germinal center of tonsil, and IgA1 positive cells were mainly localized in subepithelium of tonsil. Compared to control group, the percent of B1a cells and IgA1 positive cells was significantly higher in IgAN (P＜0.01). There was a positive correlation between Bla cells and IgA1 cells (P＜0.05). In IgAN, the percent of B1a cells in patients with hematuria and proteinuria was obviously higher than that of patients with hematuria only (P＜0.05). The number of Bla cells in IgAN patients with≥Lee's grade Ⅲ was significantly higher than that of those ＜ grade Ⅲ (P＜0.05). Conclusions IgA1 may be secreted by Bla cells in the tonsil of IgAN patients. The number of B1a cells is correlated with exacerbation of proteinuria and pathological severity, which may play an important role in pathogenesis of IgAN.
ABSTRACT
IgA plays an important role in the course of Henoch-Schonlein purpura.The current study shows that the HSP is characterized by IgA principally IgA1) depositions in the wall of dermal vessel and the renal mesangium, and IgA1 is deficient in galactose. IgA1 with aberrant glycosylation has a tendency to be self-aggregated, not to be efficiently cleared by the hepatic asialoglycoprotein receptor. It also weakens the ability of complement to remove immune complexes, and causes the exposure of new epitope and so on. All these lead to the formation of IgA1 immune complexes and the deposition in the wall of dermal vessel and the renal mesangium. IgA1 immune complexes activate complement principally through the alternative pathway, which causes inflammatory injury. In addition, various IgA autoantibodies, such as anti-endothelial cell antibodies,anticardiolipin antibodies and anti-neutrophil cytoplasmic antibodies, are also involved in the process of tissue damage of Henoch-Schonlein purpura.
ABSTRACT
IgA nephropathy is characterized by the predominant deposition of IgA in a granular fashion diffusely in the mesangial zones of glomeruli. IgA nephropathy was first described over four decades ago and is now the most common form of primary glomerular disease. Much progress has been made in the elucidation of potential pathogenetic mechanisms such as undergalactosylated IgA1 as well as in the fields of clinical features, prognosis, and treatment. This knowledge is being applied in the development of new diagnostic methods and hopefully in the future the creation of novel and rational therapeutic approaches.
Subject(s)
Glomerulonephritis, IGA , Immunoglobulin A , Kidney Failure, Chronic , PrognosisABSTRACT
In this study, IgA1 levels in the milk and serum of puerperae were compared and a correlation was established between the levels of this immunoglobulin and the occurrence of parasitism. Eighty-three paired milk and serum samples were obtained from puerperal and IgA1 levels were analyzed. In addition, the presence of intestinal parasites in stool samples from these puerperae was determined. Twelve puerperae tested positive for intestinal parasites and all their samples presented an IgA1 ELISA Index > 1. There was a correlation between serum and milk IgA1 levels and puerperae with any parasite in their stool (r = 0.6723; p = 0.0166). This finding may reinforce the importance of breast-feeding for the protection of neonates.
Subject(s)
Female , Humans , Feces/parasitology , Immunoglobulin A/analysis , Intestinal Diseases, Parasitic/diagnosis , Milk, Human/immunology , Postpartum Period , Enzyme-Linked Immunosorbent Assay , Immunoglobulin A/blood , Intestinal Diseases, Parasitic/immunology , Intestinal Diseases, Parasitic/parasitologyABSTRACT
Objective To evaluate the clinical value of detecting serum underglycosylated IgA1 in diagnosis and differentiation of lgA nephropathy (IgAN). Methods Serum underglycosylated IgA1 was isolated by microspincolumn coupled with vicia villosa lectin (VVL) from 48 cases with IgAN and 43 cases with other primary glomemlonephritis. All the patients were diagnosed by renal biopsy. Sera from 20 healthy persons were used as control group. After isolation, the eluant with rich underglycosylated lgAl was detected by incubation with biotin- labeled horseradish peroxidase (HRP) and Helix aspersa (HAA, recognizing N-acetylgalactosamine specifically)in enzyme-linked immunosorbent assay (ELISA). The sensitivity and specificity of diagnosis and differentiation of IgAN with elevated serum underglycosylated IgA1 were analyzed. Results The level of serum underglycosylated IgA1 in IgAN patients [(83.7±41.0) U] was significantly higher than that in healthy control group [(52.6±22.9) U] and the patients with other primary glomerular diseases[(49.2±27.3) U] (all P<0.01). Twenty-two cases of non-IgA mesangial proliferative glomerulonephritis accounted for 51% of other primary glomerular disease, whose underglycosylated IgA1 level [(47.6±21.5 ) U] (all P<0.01 ) was significantly lower as compared to IgAN patients. Taking the renal biopsy diagnosis as golden diagnostic criteria, the ROC curve was performed. The area under the curve was 0.797 with a standard error 0.047 (P<0.01). The sensitivity as a diagnostic test was 72.9%, with specificity 72.1% and accuracy 72.5%. Conclusion Detection of serum underglycosylated lgAl level by mierospineolumn method and ELISA assay has certain clinical value in diagnosis and differentiation of IgAN.
ABSTRACT
Bioassay of Ureaplasma urealyticum is necessary for detection as well as determination of pathogenic factors in order to understand the pathogenesis of diseases associate with ureaplasma infection. Cultivation and verification of ureaplasma is the first step of this study in the purpose of discovering sensitive method for ureaplasma detection. Cultivation of ureaplasma either in liquid or in solid media are able to detect the existence of ureaplasma in samples analyzed. However, application of PCR using specific primers to be compatible with urease gene (ure) would confirm the presence of ureaplasma. The pathogenicity of ureaplasma is potentially monitored using reporter gene as a marker for gene expression. IceC was chosen as reporter gene for ureaplasma pathogenic determination as the gene has great sensitivity, easily detectable and quantitated in simple method of ice nucleation assay. Transposon 916 (Tn916) was selected as a vector for iceC gene to transform ureaplasma. The application of recombinant Tn916-iceC which is considered as pUI, allow detection of ureaplasma activities when transform ureaplasma is tested by ice nucleation assay. It was expected that ureaplasma transformation is the manifestation of mutagenesis which interfere genes responsible for bacterial pathogenicity, in order pathogenesis of bacterial infection to be analyzed accurately. IgA1 protease is considered to be an important factor for ureaplasma pathogenicity as the enzyme is required for successful colonization. Identification of iga gene and determination of IgA1 protease activity are important for understanding the pathogenesis of ureaplasma infection. Putative iga gene of Mycoplasma genitalium was used as a reference to identify the presence of iga nucleotide sequence in U. urealyticum. Convincing evidence were obtained after PCR amplification of ureaplasma DNA using primers designed to be compatible with putative iga gene of M. genitalium followed by the discovery of 100% sequence homology of amplified ureaplasma iga gene and iga gene of M. genitalium mentioned in establish data. IgA1 protease activity of U. urealytium has been detectable in the cell rather than in media culture, suggesting that IgA1 protease is not secreted out of cell. It was proofed that IgA1 protease is membrane bound enzyme capable of digesting IgA1 in mucosal tissues of various organs and considered as potential virulence factor for ureaplasma that cause disease or gain entry to mucosal membrane. The existence of IgA1 protease activity in bacterial plasma membrane would have implication in ureaplasma management such as diagnosis and therapy of ureaplasma infection.
Subject(s)
Ureaplasma urealyticum , Ureaplasma Infections , Polymerase Chain ReactionABSTRACT
Objective To investigate the clinicopathological relation between the TNF-? and IgA nephropathy. Methods TNF-? levels in serum, urine and renal tissues of 50 patients with IgA nephropathy were measured, and 10 patients with minimal change nephrotic syndrome(MCNS) and 10 healthy subjects served as negative control group. Results The serum and urine levels of TNF-? in the patients with IgA nephropathy were significantly higher than those in the patients with MCNS and healthy subjects, and had a significant positive correlation with the degree of proteinuria and renal demage. TNF-? expression was mainly localized in the cytoplasm of the proximal renal tubular epithelial cells, and the interstitium with more monocyte-macrophages infiltration. Conclusion TNF-? took part in the onset of hematuria and proteinuria, was correlated with the degree of renal damage, and played an important role in the aggravation of IgA nephropathy.