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

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Biao Xie ◽  
Wei Zhang ◽  
Qi Zhang ◽  
Qiuju Zhang ◽  
Yupeng Wang ◽  
...  

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.

2019 ◽  
Vol 2019 ◽  
pp. 1-14
Author(s):  
Hui Yang ◽  
Jing Guan ◽  
Pei Ma ◽  
Yannan Fan ◽  
Jinye Bai ◽  
...  

Background. Henoch–Schönlein purpura nephritis (HSPN) is the principal cause of morbidity and mortality in Henoch–Schönlein purpura (HSP). However, there is no absolute consensus for the best management of severe HSPN till now. Qingzixiaoban Granule (QZXB GR), a traditional Chinese medicine formula, has been applied to treat HSP in clinical in China. However, the therapeutic effects and potential mechanism of QZXB GR on HSPN is still unknown. Methods. A Gliadin plus Indian Ink-induced HSPN mice model was established. Renal histopathologic changes and the subcutaneous hemorrhage on left legs were assessed. Hematuria and proteinuria were determined using hemocytometer and bicinchoninic acid assay, respectively. The serum circular immune complex and interleukin-6 were quantified by ELISA. Using blood biochemical analyzer, the renal biochemical parameters, including serum total protein, albumin, creatinine, and blood urea nitrogen, were measured. The deposition of immune complex in renal tissues and the lymphocyte subsets in peripheral blood and spleen was investigated by immunohistochemistry and flow cytometry. Results. QZXB GR treatment significantly ameliorated renal injury in HSPN mice, by attenuating renal histopathological changes, reducing subcutaneous hemorrhage, decreasing proteinuria/hematuria, regulating renal biochemical parameters, and inhibiting the release of serum interleukin-6. Furthermore, QZXB GR treatment significantly decreased the level of serum circular immune complex, decreased immune complex IgA and IgG deposition in renal tissue, and suppressed Th2 immunodeviation. Conclusion. QZXB GR could prevent renal injury in HSPN mice, and its renoprotective mechanism might be exerted partly through suppressing immune complexes deposition and Th2 immune deviation.


Author(s):  
Eda Didem Kurt-Şükür ◽  
Thivya Sekar ◽  
Kjell Tullus

Abstract Background Knowledge on normal progress and treatment of Henoch-Schönlein purpura nephritis (HSPN) is limited. This study reviews outcome, clinical, pathological, and therapeutic factors affecting the prognosis of HSPN patients. Methods Forty-nine children with biopsy-confirmed HSPN diagnosed between September 2008 and 2018 were included. Demographics, clinical and laboratory data, treatment, and outcome were recorded at the time of biopsy, 3, 6, 12, and 24 months and at last visit. Clinical outcome was graded according to Meadow’s criteria. Results The median age at time of biopsy was 10.1 years (IQR:5.7) and female/male ratio 24/25. At presentation, 40.8% of patients had nonnephrotic proteinuria, 18.4% nephrotic syndrome (NS), 4.1% nephritic syndrome (NephrS), and 36.7% NephrS+NS. There were 11 patients with an estimated glomerular filtration rate below 90 ml/min/1.73 m2. Biopsy specimens were classified according to International Study of Kidney Diseases in Children (ISKDC) and Oxford Classification MEST-C scoring systems. Forty-one patients received angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, 37 patients steroids, and 35 patients other immunosuppressive medications. At last visit, 24 patients had stage 1 chronic kidney disease (CKD), three stage 2 CKD, and two had stage 5 CKD. Neither clinical parameters nor ISKDC biopsy grade or treatment modalities effected the final outcome. The Oxford classification showed significantly increased segmental glomerulosclerosis in patients with unfavorable outcome. Favorable outcome was associated with shorter time from kidney involvement to biopsy and start of treatment. Conclusion A large proportion of patients continued to show signs of CKD at last follow-up while only a small proportion developed stage 5 CKD.


2018 ◽  
Vol 34 (4) ◽  
pp. 663-670 ◽  
Author(s):  
Xiao-qing Yang ◽  
Yan-jie Huang ◽  
Wen-sheng Zhai ◽  
Xian-qing Ren ◽  
Qing-yin Guo ◽  
...  

2010 ◽  
Vol 42 (4) ◽  
pp. 1023-1029 ◽  
Author(s):  
Yukihiko Kawasaki ◽  
Kazuhide Suyama ◽  
Eichi Yugeta ◽  
Masahiko Katayose ◽  
Shigeo Suzuki ◽  
...  

2021 ◽  
Vol 73 (10) ◽  
pp. 687-694
Author(s):  
Thanaporn Chaiyapak ◽  
Anirut Pattaragarn ◽  
Suroj Supavekin ◽  
Nuntawan Piyaphanee ◽  
Kraisoon Lomjansook ◽  
...  

Background: Henoch-Schönlein purpura nephritis (HSPN) is considered the systemic form of IgA nephropathy (IgAN). However, differing clinicopathological features and renal outcomes of children with IgAN and HSPN have been reported in some studies. Methods: This study retrospectively reviewed children with IgAN and HSPN younger than 18 years, between January 2004 and December 2015. The clinicopathological characteristics at diagnosis and the renal outcomes after at least 1 year of follow-up were compared between the two groups. Results: A total of 54 children, comprising 21 with IgAN and 33 with HSPN, were recruited. The children with HSPN were younger than the children with IgAN. Gross hematuria and nephritic syndrome at the initial presentation were more common in children with IgAN. Regarding the pathological findings, IgAN had greater chronicity than HSPN. After a median follow-up period from first presentation to renal outcomes measurement of 4.0 years (1.3-12.2) in children with IgAN and 4.2 years (1.1-11.4) in children with HSPN, the renal outcomes were better in the latter group. The incidence of chronic kidney disease (CKD) was 28.6% in children with IgAN and 6.1% in children with HSPN (p = 0.02). Complete recovery was observed more frequently in children with HSPN than in children with IgAN (57.1% in IgAN vs. 87.9% in HSPN, p = 0.01). Conclusions: Childhood IgAN has greater chronicity and worse renal outcomes than childhood HSPN, with a lower rate of complete recovery and a higher frequency of CKD. We recommend long-term follow-up for CKD in children with IgAN.


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