scholarly journals Circulating serum lectins of patients with IgA nephropathy stimulate IL-6 release from mesangial cells.

1997 ◽  
Vol 8 (2) ◽  
pp. 208-213
Author(s):  
C Libetta ◽  
T Rampino ◽  
G Palumbo ◽  
C Esposito ◽  
A Dal Canton
Keyword(s):  
Affinity Chromatography ◽  
Iga Nephropathy ◽  
Mesangial Cells ◽  
Lectin Binding ◽  
Normal Serum ◽  
In Vitro Studies ◽  
Human Mesangial Cells ◽  
Serum Activity ◽  
Peripheral Leukocytes

Previously, the authors reported that the serum of patients with immunoglobulin (Ig) A nephropathy stimulated peripheral leukocytes, and this effect was inhibited by nominal haptens for lectins. In vitro studies have shown that lectins can bind to rat mesangial cells and cause their activation. This study was performed to investigate whether the serum of IgA nephropathy patients contains lectins that activate mesangial cells, i.e., induce release of interleukin (IL)-6, a nephritogenic cytokine. The serum of patients was adsorbed by affinity chromatography on resins loaded with lectin-binding sugars. After adsorption, serum supernatant was collected and the resins were then eluted. Human mesangial cells were conditioned with native serum, post-adsorption supernatant, and eluate (all three at 10%) for 24 h, and the release of IL-6 was determined by ELISA. Normal serum was used as control. Incubation of mesangial cells with IgA nephropathy patients serum raised average IL-6 release from 8.5 pg/mL to 274.1 pg/mL. Adsorption in beta-D-glucose and N-acetyl-D-glucosamine caused a fall in the activity of patients' serum, to 17.0 and 63.7 pg/mL, respectively, and the activity lost was recovered in the eluate (185.2 and 142.7 pg/mL, respectively). Neither adsorption on N-acetyl-D-galactosamine nor on fucosylamine was associated with any effect on serum activity; accordingly, no activity was found in the eluates. Serum of patients with non-IgA mesangiocapillary nephritis did not stimulate mesangial cells. These results show that the serum of IgA nephropathy patients contains specific lectins that stimulate IL-6 nephropathy by mesangial cells and are, therefore, potential nephritogenic.

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.

IgA1 isolated from Henoch‐Schönlein purpura children promotes proliferation of human mesangial cells in vitro

2019 ◽  
Vol 43 (7) ◽  
pp. 760-769 ◽  
Author(s):  
Qin Zhang ◽  
Lili Yan ◽  
Mingyu Chen ◽  
Ming Gui ◽  
Ling Lu ◽  
...  
Keyword(s):  
Mesangial Cells ◽  
Henoch Schonlein Purpura ◽  
Human Mesangial Cells ◽  
Schonlein Purpura ◽  
Henoch Schönlein Purpura

scholarly journals IgA1 immune complexes from pediatric patients with IgA nephropathy activate cultured human mesangial cells

2011 ◽  
Vol 26 (11) ◽  
pp. 3451-3457 ◽  
Author(s):  
Jan Novak ◽  
Leona Raskova Kafkova ◽  
Hitoshi Suzuki ◽  
Milan Tomana ◽  
Karel Matousovic ◽  
...  
Keyword(s):  
Iga Nephropathy ◽  
Immune Complexes ◽  
Pediatric Patients ◽  
Mesangial Cells ◽  
Human Mesangial Cells

scholarly journals Serum IgA1 from IgA nephropathy patients induces apoptosis in podocytes through direct and indirect pathways

2007 ◽  
Vol 30 (6) ◽  
pp. 240 ◽  
Author(s):  
Cheng Wang ◽  
Hui Peng ◽  
Hua Tang ◽  
Xun Liu ◽  
Zhujiang Chen ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Affinity Chromatography ◽  
Mrna Expression ◽  
Iga Nephropathy ◽  
Real Time Pcr ◽  
Molecular Sieve ◽  
Mesangial Cells ◽  
Tunel Staining ◽  
Fas Mrna ◽  
Fas L

Purpose: To investigate apoptosis of podocytes induced by IgA1 isolated from IgA nephropathy (IgAN) patients through direct and indirect pathways. Methods: Jacalin affinity chromatography and Sephacryl S-200 molecular sieve chromatography were used to isolate IgA1 from blood of IgAN patients made as aggregated IgA1 (aIgA1). Podocytes were incubated with aIgA1 or special treated medium from mesangial cells after co-incubation with aIgA1 from IgAN patients. Apoptosis of podocytes was assessed by TUNEL staining and flow cytometry. Real-time PCR was used to detect the mRNA expression of Bcl-2, Bax, Fas and Fas-L. Results: AIgA1 from IgAN patients induced more apoptosis of podocytes by both time and concentration-dependent patterns than control (30.5±5.4% vs 20.5±4.5, respectively, P < 0.05). The percentage of apoptotic podocytes exposed to treated medium was higher than control (28.5±5.9 % vs 20.5±4.5%, respectively, P < 0.05). The level of normalized Fas mRNA expression in podocytes exposed to aIgA1 was 2.4-fold higher than control (P < 0.05), while the level in podocytes exposed with treated medium was 1.89-fold higher than control (P < 0.05), and the level of normalized Bcl-2 mRNA expression in this group was 72% lower than control (P < 0.05) Conclusion: IgA1 from IgAN patients may induce apoptosis of podocytes through direct and indirect pathways. IgA1 may accelerate progression of IgAN by inducing apoptosis of podocytes.

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 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.

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