scholarly journals Immune Characteristics of IgA Nephropathy With Minimal Change Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Huixian Li ◽  
Wanhong Lu ◽  
Haiyun Li ◽  
Xiaoling Liu ◽  
Xue Zhang ◽  
...  
Keyword(s):  
Iga Nephropathy ◽  
Minimal Change Disease ◽  
Estimated Glomerular Filtration Rate ◽  
Mesangial Cells ◽  
Minimal Change ◽  
Substantial Evidence ◽  
Pathological Characteristics ◽  
High Degree ◽  
Degree Of Heterogeneity

Background: IgA nephropathy (IgAN) has a high degree of heterogeneity in clinical and pathological features. Among all subsets of IgAN, the pathogenesis of IgAN with minimal change disease (MCD-IgAN) remained controversial.Methods: We analyzed the clinical and pathological characteristics of MCD-IgAN patients in a retrospective cohort. Patients diagnosed with IgAN, excluding MCD-IgAN, were randomly selected as controls. Levels of plasma galactose-deficient IgA1 (GdIgA1), IgG autoantibodies against GdIgA1, GdIgA1 deposition in the glomerulus, and inflammatory reactivity of circulating poly-IgA1 complexes to cultured mesangial cells were evaluated.Results: Patients with MCD-IgAN had significantly higher levels of proteinuria and estimated glomerular filtration rate (eGFR), lower levels of albumin and urine blood cells, and milder histological lesions by a light microscope compared to IgAN patients, which bears a resemblance to MCD. Lower levels of GdIgA1 (3.41 ± 1.68 vs. 4.92 ± 2.30 μg/ml, p = 0.009) and IgG antiglycan autoantibodies (23.25 ± 22.59 vs. 76.58 ± 71.22 IU/ml, p < 0.001) were found in MCD-IgAN patients than those in IgAN controls. Meanwhile, weaker fluorescence intensities of both IgA and GdIgA1 were observed in the glomerulus of MCD-IgAN patients compared to those in IgAN patients. Furthermore, poly-IgA1 complexes from MCD-IgAN patients induced weaker inflammatory effects on cultured mesangial cells than those from IgAN patients in vitro.Conclusion: The results demonstrated that MCD-IgAN cases represent a dual glomerulopathy, namely, mild IgAN with superimposed MCD, which furthermore provides substantial evidence for the corticosteroids therapy in MCD-IgAN patients as the guidelines recommended.

Mass spectrometry-based circulating IgA1 complexes screening driven identification of IgA-alpha-1-microglobulin complex in IgA nephropathy

2020 ◽  
Author(s):  
Boyang Xu ◽  
Li Zhu ◽  
Qingsong Wang ◽  
Yanfeng Zhao ◽  
Meng Jia ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Iga Nephropathy ◽  
Cell Injury ◽  
Mesangial Cell ◽  
Mesangial Cells ◽  
Independent Population ◽  
Tubulointerstitial Lesions ◽  
Noninvasive Biomarker

Abstract Background IgA nephropathy (IgAN) is characterized by predominant IgA deposition in the glomerular mesangium. Previous studies proved that renal-deposited IgA in IgAN came from circulating IgA1-containing complexes (CICs). Methods To explore the composition of CICs in IgAN, we isolated CICs from IgAN patients and healthy controls, and then quantitatively analyzed them by mass spectrometry. Meanwhile, the isolated CICs were used to treat human mesangial cells to monitor mesangial cell injury. Taken together the proteins content and injury effects, the key constituent in CICs was identified. Then, the circulating levels of identified key constituent-IgA complex were detected in an independent population by an in-house-developed ELISA. Results By comparing the proteins of CICs between IgAN patients and controls, we found that 14 proteins showed significantly different levels. Among them, alpha-1-microglobulin content in CICs was associated with not only in vitro mesangial cell proliferation and MCP-1 secretion but also in vivo eGFR levels and tubulointerstitial lesions in IgAN patients. Moreover, we found alpha-1-microglobulin was prone to bind aberrant glycosylated IgA1. Additionally, an elevated circulating IgA-alpha-1-microglobulin complex levels were detected in an independent IgAN population, and IgA-alpha-1-microglobulin complex levels were correlated with hypertension, eGFR levels and Oxford-T scores in these IgAN patients. Conclusions Our results suggest that the IgA-alpha-1-microglobulin complex is an important constituent in CICs, and that circulating IgA-alpha-1-microglobulin complex detection might serve as a potential noninvasive biomarker detection method for IgAN.

Comparison between patients with IgA nephropathy with minimal change disease and patients with minimal change disease

2016 ◽  
Vol 85 (2016) (05) ◽  
pp. 273-281 ◽  
Author(s):  
Xiao-Wei Li ◽  
Shui-Qin Cheng ◽  
Shao-Shan Liang ◽  
Wei-Bo Le ◽  
Cai-Hong Zeng ◽  
...  
Keyword(s):  
Iga Nephropathy ◽  
Minimal Change Disease ◽  
Minimal Change

Clinicopathologic features and treatment response in nephrotic IgA nephropathy with minimal change disease

2013 ◽  
Vol 80 (07) ◽  
pp. 79 ◽  
Author(s):  
Keng Thye Woo ◽  
Kok Seng Wong ◽  
Hui Lin Choong ◽  
Marjorie Foo ◽  
York Moi Chin ◽  
...  
Keyword(s):  
Treatment Response ◽  
Iga Nephropathy ◽  
Minimal Change Disease ◽  
Minimal Change ◽  
Clinicopathologic Features

Long-term outcome of IgA nephropathy with minimal change disease: a comparison between patients with and without minimal change disease

2015 ◽  
Vol 29 (4) ◽  
pp. 567-573 ◽  
Author(s):  
Xiao-Wei Li ◽  
Shao-Shan Liang ◽  
Wei-Bo Le ◽  
Shui-Qin Cheng ◽  
Cai-Hong Zeng ◽  
...  
Keyword(s):  
Iga Nephropathy ◽  
Minimal Change Disease ◽  
Minimal Change ◽  
Term Outcome ◽  
Long Term Outcome

scholarly journals Sialylation of IgG inhibits the formation of galactose-deficient IgA1-containing immune complexes and protects mesangial cells from injury in IgA nephropathy

2022 ◽  
Vol 23 (1) ◽  
Author(s):  
Youxia Liu ◽  
Hongfen Li ◽  
Huyan Yu ◽  
Fanghao Wang ◽  
Junya Jia ◽  
...  
Keyword(s):  
Iga Nephropathy ◽  
B Lymphocytes ◽  
Immune Complexes ◽  
Mononuclear Cells ◽  
Mesangial Cells ◽  
Healthy Controls ◽  
Peripheral Blood Mononuclear ◽  
Tnf Α ◽  
Inflammatory State

Abstract Background The addition of sialic acid alters IgG from a pro-inflammatory state to an anti-inflammatory state. However, there is a lack of research on the changes of IgG sialylation in IgA nephropathy (IgAN). Methods This study included a total of 184 IgAN patients. The sialylated IgG (SA-IgG), IgG-galactose-deficient IgA1 complex (IgG-Gd-IgA1-IC), IL-6, TNF-α, and TGF-β were detected using commercial ELISA kits. SA-IgG, non-sialylated IgG (NSA-IgG), sialylated IgG-IgA1 complex (SA-IgG-IgA1), and non-sialylated IgG-IgA1 complex (NSA-IgG-IgA1) were purified from IgAN patients and healthy controls (HCs). Results The mean SA-IgG levels in plasma and B lymphocytes in IgAN patients were significantly higher than those of healthy controls. A positive correlation was found between SA-IgG levels in plasma and B lymphocytes. In vitro, the results showed that the release of IgG-Gd-IgA1-IC was significantly decreased in peripheral blood mononuclear cells (PBMCs) cultured with SA-IgG from both IgAN patients and healthy controls. The proliferation ability and the release of IL-6, TNF-α, and TGF-β in human mesangial cells (HMCs) were measured after stimulating with SA-IgG-IgA1-IC and NSA-IgG-IgA1-IC. The mesangial cell proliferation levels induced by NSA-IgG-IgA1-IC derived from IgAN patients were significantly higher than those caused by SA-IgG-IgA1-IC derived from IgAN patients and healthy controls. Compared with NSA-IgG-IgA1 from healthy controls, IgAN-NSA-IgG-IgA1 could significantly upregulate the expression of IL-6 and TNF-α in mesangial cells. The data showed that there weren’t any significant differences in the levels of IL-6, TNF-α, and TGF-β when treated with IgAN-SA-IgG-IgA1 and HC-NSA-IgG-IgA1. Conclusions The present study demonstrated that the sialylation of IgG increased in patients with IgA nephropathy. It exerted an inhibitory effect on the formation of Gd-IgA1-containing immune complexes in PBMCs and the proliferation and inflammation activation in mesangial cells.

scholarly journals P0468RENAL OUTCOME AND MORTALITY OF GLOMERULONEPHRITIS IN A THAI TERTIARY CARE CENTER

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Chitimaporn Janphram ◽  
Chagriya Kitiyakara
Keyword(s):  
Multiple Myeloma ◽  
Diabetic Nephropathy ◽  
Lupus Nephritis ◽  
Iga Nephropathy ◽  
Immune Complex ◽  
Membranous Nephropathy ◽  
Minimal Change Disease ◽  
Kidney Biopsy ◽  
Minimal Change ◽  
Different Types

Abstract Background and Aims Glomerulonephritis (GN) is a common cause of End-stage renal disease (ESRD) in Asia and around the world. Most studies from renal registries have focused on the prevalence or clinical characteristics of patients with GN. Only a few registry-based data have focused on mortality and ESRD risks of different types of GN. There is limited data from low to middle income countries or from Southeast Asia. The objectives of this study were to evaluate the mortality and ESRD rates among patients with different types of GN referred for a kidney biopsy at a Thai tertiary care hospital. Method In this retrospective study, the data of patients (n=1,025) referred for a kidney biopsy at Ramathibodi Hospital from 1 January 2011 to 31 December 2017 were reviewed. Patients were classified in to 11 different types of GN. Patient death and cause of death data was obtained from National Census office. ESRD data was obtained from the Thailand Nephrology Society ESRD registry which includes all patients on renal replacement therapies for greater than 3 months. Results Patients with inadequate specimen (n=66) or non-glomerular diseases (n=95) were excluded. Data from 864 patients with GN was analyzed. The age at kidney biopsy was 43.9 ± 16.8 years, median eGFR (CKD-EPI) was 42 (IQR 13-83) mL/min/1.73m2. The male:female ratio was 0.6. The prevalence of GN were: Lupus nephritis (26.8%), IgA nephropathy (18.2%), focal segmental glomerulosclerosis (FSGS 12.6 %), membranous nephropathy (11.9 %), diabetic nephropathy (10.8%), minimal change disease (9.7%), hypertensive nephrosclerosis (4.3%), pauci-immune complex glomerulonephritis (2.3%), membranoproliferative glomerulonephritis (MPGN 1.6%) and multiple myeloma (1.4%) Median time follow up was 42 (IQR 23-62) months. Overall mortality was 13 %. Lupus nephritis accounted for highest proportion of all deaths (25%), followed by diabetic nephropathy (19.1%), FSGS (9%). Listed causes of deaths were: sepsis 22% and chronic kidney disease 8%. Mortality rates by disease were: multiple myeloma (50%), diabetic nephropathy (28.7%), MPGN (21.4%), pauci-immune complex GN (20%), hypertensive nephrosclerosis (15.8%), lupus nephritis (14.6%), membranous nephropathy (8.7%), FSGS (8.2%), minimal change disease (5.8%), IgA nephropathy (4.4%) The incidence of ESRD was 14 %. LN accounted for the highest proportion (29%) of all ESRD, followed by IgA nephropathy (14%), and membranous nephropathy (13%). The rates of ESRD by disease were: multiple myeloma (33.3%), lupus nephritis (15%), membranous nephropathy (14.5%), minimal change disease (14.3%), MPGN (14.2%), IgA nephropathy (10.1%), FSGS (10.1%), diabetic nephropathy (7.4%), pauci-immune complex glomerulonephritis (5%), hypertensive nephroclerosis (2.6%). Conclusion Lupus nephritis is the most common GN and accounted for the highest proportion of all deaths and ESRD in this Thai cohort. IgA nephropathy is the most common primary GN and an important cause of ESRD, but the mortality rate is low compared to other GN. Membranous nephropathy has comparable prevalence to FSGS, but is a more important contributor to ESRD. Diabetic nephropathy has higher rate of mortality than ESRD. Multiple myleloma has the highest rate of both death and ESRD.

scholarly journals The TLR4-MyD88-NF-κB pathway is involved in sIgA-mediated IgA nephropathy

2020 ◽  
Vol 33 (6) ◽  
pp. 1251-1261 ◽  
Author(s):  
Junjun Zhang ◽  
Yiming Mi ◽  
Ruwen Zhou ◽  
Zhangsuo Liu ◽  
Bo Huang ◽  
...  
Keyword(s):  
Iga Nephropathy ◽  
Mesangial Cells ◽  
Immunofluorescence Assay ◽  
Kidney Damage ◽  
Secretory Iga ◽  
Tnf Α ◽  
Mesangial Area ◽  
Enhanced Expression ◽  
Better Than

AbstractPrevious studies have shown that secretory IgA (sIgA) was critically involved in IgA nephropathy (IgAN) immune responses. Toll-like receptors (TLRs), especially TLR4 which participates in mucosal immunity, may be involved in the pathogenesis of IgAN. The purpose of this study was to investigate whether sIgA and TLR4 interact to mediate kidney damage in IgAN patients. IgAN patients with positive sIgA deposition in renal tissues were screened by immunofluorescence assay. Patient salivary sIgA (P-sIgA) was collected and purified by jacalin affinity chromatography. Salivary sIgA from healthy volunteers was used as a control (N-sIgA). Expression of TLR4, MyD88, NF-κB, TNF-α, IL-6, and MCP-1 were detected in the mesangial area of IgAN patients by immunohistochemistry, the expression levels in patients with positive sIgA deposition were higher than that with negative sIgA deposition. Human renal mesangial cells (HRMCs) were cultured in vitro, flow cytometry showed that P-sIgA bound HRMCs significantly better than N-sIgA. HRMCs were cultured in the presence of sIgA (400 μg/mL) for 24 h, compared with cells cultured with N-sIgA, HRMCs cultured in vitro with P-sIgA showed enhanced expression of TLR4, increased secretion of TNF-α, IL-6, and MCP-1, and increased expression of MyD88/NF-κB. TLR4 shRNA silencing and NF-κB inhibition both reduced the ability of HRMCs to synthesize TNF-α, IL-6, and MCP-1. Our results indicate that sIgA may induce high expression of TLR4 in HRMCs and further activate downstream signalling pathways, prompting HRMCs to secrete multiple cytokines and thereby mediating kidney damage in IgAN patients.

Collectin11 and Complement Activation in IgA Nephropathy

2021 ◽  
pp. CJN.04300321
Author(s):  
Min Wei ◽  
Wei-yi Guo ◽  
Bo-yang Xu ◽  
Su-fang Shi ◽  
Li-jun Liu ◽  
...  
Keyword(s):  
Iga Nephropathy ◽  
Complement Activation ◽  
Immune Complexes ◽  
Mesangial Cells ◽  
Kidney Injury ◽  
Lectin Pathway ◽  
Independent Manner ◽  
Proximity Ligation ◽  
Injury Model

Background and objectives: IgA nephropathy is the most common primary glomerulonephritis worldwide. Previous research demonstrated that collectin11, an initiator of complement lectin pathway, was involved in both acute kidney injury and chronic tubulointerstitial fibrosis. Here, we investigated the potential role of collectin11 in the pathogenesis of IgA nephropathy. Design, setting, participants, and measurements: The deposition of collectin11 and other complement proteins was detected in glomeruli of 60 participants with IgA nephropathy by immunofluorescence. In vitro, human mesangial cells were treated with IgA1-containing immune complexes derived from participants with IgA nephropathy. Then, the expression of collectin11 in mesangial cells was examined by RT-qPCR and immunofluorescence. The codeposition of collctin11 with IgA1 or C3 on mesangial cells was detected by immunofluorescence and proximity ligation assays. Results: 37% participants with IgA nephropathy (22/60) showed codeposition of collectin11 with IgA in the glomerular mesangium. Using an injury model of mesangial cells, we demonstrated that IgA1-immune complexes derived from participants with IgA nephropathy increased the secretion of collectin11 in mesangial cells with the subsequent deposition of collectin11 on the cell surface via the interaction with deposited IgA1-immune complexes. In vitro, we found that collectin11 bound to IgA1-immune complexes in a dose-dependent but calcium-independent manner. Furthermore, deposited collectin11 initiated the activation of complement and accelerated the deposition of C3 on mesangial cells. Conclusions: In situ-produced collectin11 by mesangial cells might play an essential role in kidney injury in a subset of patients with IgA nephropathy through the induction of complement activation.

scholarly journals Macromolecular IgA1 taken from patients with familial IgA Nephropathy or their asymptomatic relatives have higher reactivity to mesangial cells in vitro

2009 ◽  
Vol 75 (12) ◽  
pp. 1330-1339 ◽  
Author(s):  
Ka Ying Tam ◽  
Joseph C.K. Leung ◽  
Loretta Y.Y. Chan ◽  
Man Fai Lam ◽  
Sydney C.W. Tang ◽  
...  
Keyword(s):  
Iga Nephropathy ◽  
Mesangial Cells
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