Advances in genetics of IgA vasculitis / 国际儿科学杂志

IgA vasculitis(IgAV)is a systemic vasculitis characterized mainly by deposits of IgA, which can involve multiple systems such as skin, joints, digestive tract and kidney.When the kidney is damaged, it is often called Henoch-Sch?nlein purpura nephritis, which is a common secondary glomerulonephritis in children.The specific etiology and pathogenesis of IgAV have not been very clear so far, and further studies are needed.With the development of genomics, the researchers continue to study IgAV from the gene level, and realize that HLA is the most important genetic factor in its pathogenesis.In recent years, related genetic research methods have been extended to genome-wide association studies, and the occurrence and development process of IgAV has been analyzed from the epigenetic aspect.This article reviews advances in genetics of IgAV, which will provide important information for understanding the pathogenesis of IgAV and predicting the occurrence of high-risk individuals, disease severity and kidney damage.

Progress of the protective mechanism of vitamin D on chronic kidney disease / 国际儿科学杂志

1,25(OH) 2 vitamin D 3 is the most effective status of vitamin D in the body.It will play a biological active role when it combines with the receptor of vitamin D. It is common in the chronic kidney disease patients who are lack of vitamin D. The research finds that among the chronic kidney disease patients, in addition to the classic role of vitamin D in regulating calcium and phosphorus metabolism, it can also protect the kidney and delay the progress of chronic kidney disease by blocking the renin-angiotensin system, inhibiting inflammation, reducing podocyte damage and delaying renal fibrosis, etc.This article summarizes the protection mechanism of Vitamin D in the chronic kidney diseases.

The significance of follicular helper T cells and galactose-deficient IgA 1 in the pathogenesis of Henoch-Sch?nlein purpura in children / 国际儿科学杂志

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.

Progress in the pathogenesis of Henoch-Sch?nlein purpura nephritis and IgA nephropathy in children / 国际儿科学杂志

Henoch-Sch?nlein purpura nephritis and IgA nephropathy are both characterized by extensive deposition of IgA in the mesangial area.In recent years, the researches on the pathogenesis of the two diseases have made significant progress.It was confirmed that the pathogenesis included the aberrantly glycosylated IgA1, abnormal complement activation, cellular immune imbalance and cytokine production disorder, genetic factors and so on.Furthmore, some other immunopathogenic mechanisms have a breakthrough on endothelial cell particles, extracellular trapping nets, podocyte autophagy and abnormal peptide lineage, offering new ideas for diagnosis and treatment of disease.This paper will review the above pathogenesis.

Progress of T helper cell 17,regulatory T cell,podocyte injury and primary glomerular disease / 国际儿科学杂志

In recent years,T helper cell 17(Th17),regulatory T cell(Treg) and podocyte injury attrac-ted widespread attention in the pathogenesis of primary glomerular disease. Th17 cells have the function of re-cruiting neutrophils and macrophages to the infected tissue through the secretion of cytokines such as IL-17. Treg cells have immune function, mediated immune tolerance, protecting the body against inflammatory injury. The imbalance of Th17 cells increase and Treg cells decrease could play an important role in the pathogenesis and progression of primary glomerular disease. As the important part of the glomerular filtration barrier,podocyte be-comes the focus in recent years. Study on relationship among Th17,Treg,podocyte injury and primary glomeru-lar disease will provide more theoretical basis for the prevention and treatment of primary glomerular disease.

Relationship between renal pathology and clinical manifestations in children with Henoch - Schonlein purpura nephritis / 中华实用儿科临床杂志

Objective To investigate the correlations between the clinical manifestations based on pathologic grades and renal pathological features of Henoch - Schonlein purpura nephritis(HSPN)in children. Methods The clinical data of 77 patients with HSPN in the Department of Nephrology,Anhui Provincial Children's Hospital from Ja-nuary 2004 to March 2014 were retrospectively analyzed. The relationship between clinical manifestation and pathologi-cal features was analyzed. Results Among the 77 patients,21 cases(27. 3% )had both abdominal symptoms,and ar-thritis was reported in 15 cases(19. 5% ),28 cases(36. 4% )had abdominal symptoms and arthritis,and 13 cases (16. 9% )had no such symptoms. Hematuria and proteinuria were the most common clinical types[48. 1%(37 / 77 ca-ses)],followed by simple hematuria or proteinuria[27. 3%(21 / 77 cases)],nephrotic syndrome[23. 4%(18 / 77 ca-ses)],and chronic nephritis[1. 3%(1 / 77 cases)]. The major of pathological changes in HSPN were grade Ⅱ[46. 8%(36 / 77 cases)]and grade Ⅲ[45. 5%(35 / 77 cases)],the minority of them were grade Ⅰ[6. 5%(5 / 77 cases)]and grade Ⅳ[1. 3%(1 / 77 cases)]. The severity of urine protein was positively associated with pathologic classification (r s = 0. 472,P = 0. 000). According to the glomerular deposition of immune complex,there were 6 types. The percen-tage of deposition of IgA + IgM was 62. 3%(48 / 77 cases),IgA + IgG + IgM was 19. 5%(15 / 77 cases),IgA 14. 3%(11 / 77 cases),that of IgA + IgG 1. 3%(1 / 77 cases),and the IgM 1. 3%(1 / 77 cases),no Ig 1. 3%(1 / 77 cases). In these cases,76. 6%(59 / 77 cases)had complements C3 deposition;pathologic stage characterized by Ⅲ level and a-bove were common[54. 2%(32 / 59 cases)],Ⅱ level 42. 2%(25 / 29 cases),Ⅰ level 3. 4%(2 / 59 cases). Among the different types of immune complex depositions,there was no statistically significant difference in pathological types of distribution,while the clinical type and complements C3 deposition were significantly associated with pathologic classifi-cation(rs = 0. 361,P = 0. 001). Sixty - two cases were rated as level 1(80. 5% ),and 15 cases was level 2(19. 5% );in different clinical group,rating in glomeruli was statistically different(χ2 = 17. 2,P = 0. 004). Renal tubular interstitial rating of all the patients were level 1(100% ). Conclusions The severity of urine protein,complements C3 deposition is associated with pathologic classification. Pathologic classification can basically reflect the renal damage in HSPN.

Function of CD4(+) CD25(+) regulatory T cells in Henoch-Schonlein purpura nephritis in children / 中华儿科杂志

<p><b>OBJECTIVE</b>To investigate the levels and functions of CD4(+)CD25(+) regulatory T cells and specific transcription factor Foxp3 and Th17 cells related cytokine in peripheral blood mononuclear cells (PBMC) and renal tissues, and explore their roles in pathogenesis of Henoch-Schonlein purpura nephropathy (HSPN) in children.</p><p><b>METHOD</b>From March, 2011 to March, 2013, 30 cases of HSPN children underwent renal biopsy and were treated in Guiyang Children's Hospital were enrolled into this study. Ten healthy children who underwent health check up were enrolled as blood sample control group. The normal kidney tissue specimens were taken from 5 children who underwent surgery for urologic disorders were used as renal sample control group. The circulating proportions of CD4(+)CD25(+) regulatory T cells in PBMC of 30 cases of HSPN children and 10 cases of control group were determined by flow cytometry, respectively.Reverse transcription-polymerase chain reaction (RT-PCR) were used to analyze the mRNA expressions of IL-17, IL-1β and Foxp3 in PBMC. The expression of IL-17 and IL-1β in renal tissue of HSPN and control group were measured by immunohistochemistry. CD4(+)CD25(+) regulatory T cells, Foxp3, IL-17, IL-1β expression were analyzed and compared in HSPN group and control groups respectively.</p><p><b>RESULT</b>Thirty cases of HSPN pathological classification were as follows: type I was found in 0 case; type II in 9 cases; type III in 16 cases; type IV in 5 cases; type V in 0 case. The circulating proportions of CD4(+)CD25(+)/CD4(+)T cells and the CD4(+)CD25(+)Foxp3(+)Treg/CD4(+)T cells level were (5.84 ± 0.78)%, (1.01 ± 0.46) % in HSPN groups were substantially lower than those in control group. All these two differences had statistical significance (t = 27.200, 33.260, P < 0.05). The mRNA levels of IL-17, IL-1β in HSPN groups (0.86 ± 0.01,0.71 ± 0.01) were higher than those in control group (t = 25.000, 31.840, all P < 0.05). Foxp3 mRNA expression in HSPN groups (0.24 ± 0.02) were significantly lower than those in control group (t = 21.690, P < 0.05). Protein expression of IL-17 and IL-1β in renal tissues of HSPN children (13.31 ± 0.54, 11.56 ± 0.28) were significantly stronger than those in the control group (t = 27.6, 14.0, all P < 0.01). The highest level of protein expression of IL-17 and IL-1β in renal biopsy of HSPN was in type IV (IV>III>II, F = 545.800, 262.500, all P < 0.01).</p><p><b>CONCLUSION</b>The disorder of quantity and function of CD4(+)CD25(+) regulatory T cells, and increase in levels of IL-17, IL-1β (cytokine related to Th17 cells) may play important roles in pathogenesis of HSPN in children; increased protein expression of IL-17, IL-1β in renal tissue may contribute to the development of renal pathological damage in HSPN children.</p>

Study on antisense phosphorothioate oligodeoxynudeotide resistance to influenza A virus infection in vitro / 中华微生物学和免疫学杂志

Objective To investigate the antiviral effects of antisense phosphorothioate oligodeoxynucleotide (ASODN)in 9HTEO infected with influenza A virus (IFAV) in vitro. Methods The ASODN which complemented to genomic PB1, M2, NS, PB2, HA mRNA of IFAV was used to investigate antiviral effection in vitro. The cytopathic effect (CPE) was observed, and the cell survival rates were measured by MTF assay, plaque assay, RT-PCR, Western blot and Immunofluorescence were performed to test anti-viral efficiency of PB1, M2, NS in cells mRNA and protein level. Results 9HTEO cells infected with IFAV almost all died when the multipicity of infection (MOI) is aboved after 5 days cell culture. The ASODN could increase the cell survival rates. The IFAV PB1, M2, NS significantly reduced CPE of IFAV infected 9HTEO cells, reduced the viral replication of IFAV in the cells (P <0.05). Conclusion The ASODN which targeted the mRNA of IFAV gene showed a significant and specific anti-IFAV effect both in mRNA and protein level in cells culture system. The study indicates that the PB1, M2 and NS mRNA may play an important role in regulating IFAV replication, and ASODN may have inhibitory activity on IFAV replication. The results established the basis for further study on new drugs against IFAV infection include the highly pathogenic H5N1 influenza virus.