Expression of CD19<sup>+</sup>CD5<sup>+</sup>B Cells and IgA1-positive cells in Tonsillar Tissues of IgA Nephropathy Patients

Wu, Gang; Peng, You; Liu, Hong; Hou, Qi Di; Liu, Fu You; Chen, Nan Lan; Bi, Huixin

doi:10.3109/0886022x.2011.552150

Cited by 7 publications

(5 citation statements)

References 21 publications

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“…CD19+ B cells are believed to be the main sources of IgA production and may contribute to the onset and progression of IgAN 10,11 . In this study, we at first conducted a global RNA sequencing analysis in B cells from patients with IgAN and healthy controls to identify a subset of mRNA transcripts with expression levels correlated with IgAN susceptibility.…”

Section: Discussionmentioning

confidence: 99%

“…The correlation between ST6Gal1 and Gd-IgA1 levels. ST6Gal1 levels showed a significantly positive correlation with Gd-IgA1 levels T score (T0/T1/T2) 21 (42)/24 (48)/5 (10) 23 (46)/22 (44)/5 (10) .92…”

Section: Rst6gal1 Up-regulated C1galt1 Mrna Expression In Pbmcs From ...mentioning

confidence: 94%

“…ST6Gal1 levels showed significantly positive correlations with proteinuria (A), total IgA levels (B), C3a (C), Bb (D), C4d (E) and C5b-9 (F) CD19+ B cells are believed to be the main sources of IgA production and may contribute to the onset and progression of IgAN. 10,11 In this study, we at first conducted a global RNA sequencing analysis in B cells from patients with IgAN and healthy controls to identify a subset of mRNA transcripts with expression levels correlated with IgAN susceptibility. Furthermore, we cultured human PBMCs to explore molecular mechanism driving Gd-IgA1 production.…”

Section: F I G U R Ementioning

confidence: 99%

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ST6Gal1 is up‐regulated and associated with aberrant IgA1 glycosylation in IgA nephropathy: An integrated analysis of the transcriptome

Liu

Wang

Zhang

et al. 2020

J Cellular Molecular Medi

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Galactose‐deficient IgA1 (Gd‐IgA1) plays a crucial role in the development of Immunoglobulin A nephropathy (IgAN), however, the underlying pathogenic mechanisms driving Gd‐IgA1 production in B cells are not well understood. In this study, RNA‐seq analysis identified 337 down‐regulated and 405 up‐regulated genes in B cells from 17 patients with IgAN and 6 healthy controls. Among them, ST6Gal1, which was associated with IgAN in a previous genome‐wide association study (GWAS), was up‐regulated in IgAN and significantly positive correlated with elevated Gd‐IgA1. In addition, we identified increased plasma ST6Gal1 levels in 100 patients with IgAN, which were associated with higher levels of proteinuria, plasma IgA, Gd‐IgA1 levels, greater degrees of systemic complement activation including C3a, Bb, C4d, MAC and a lower proportion classified as C2 grade (crescent proportion ≥25%). Interesting, in vitro, recombinant ST6Gal1 (rST6Gal1) exposure reduced the production of Gd‐IgA1 in cultured peripheral blood mononuclear cells from IgAN patients. rST6Gal1 stimuli also increased expression of C1GALT1, which were well‐known proportional to the decrease in galactose deficiency of IgA1. In conclusions, we identified increased plasma ST6Gal1 levels and the association of ST6Gal1 with disease severity of IgAN. Additionally, rST6Gal1 administration in vitro increased expression of C1GALT1 and reduced the production of Gd‐IgA1.

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Section: Discussionmentioning

confidence: 99%

Section: Rst6gal1 Up-regulated C1galt1 Mrna Expression In Pbmcs From ...mentioning

confidence: 94%

Section: F I G U R Ementioning

confidence: 99%

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ST6Gal1 is up‐regulated and associated with aberrant IgA1 glycosylation in IgA nephropathy: An integrated analysis of the transcriptome

Liu

Wang

Zhang

et al. 2020

J Cellular Molecular Medi

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“…Furthermore, the reconstitution of IgAN by transfusion of murine spleen cells without CD90+ pan T cells and transfusion of CD19+ cells in SCID mice indicates that the responsible B cells are involved in nephritogenic IgA synthesis in a T-cell-independent manner (181). A Chinese clinical cohort study demonstrated that the levels of tonsillar CD19+CD5+B cells of patients with IgAN were positively associated with the severity of renal histopathology (182). Another study investigated the features of CD19+CD5+ B cells in the circulation, ascites, and biopsy tissues of patients with IgAN.…”

Section: Role Of B Cells In Igan Pathogenesismentioning

confidence: 99%

The Role of Immune Modulation in Pathogenesis of IgA Nephropathy

Chang

2020

Front. Med.

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IgA nephropathy (IgAN) is the most prevalent primary glomerulonephritis worldwide, with diverse clinical manifestations characterized by recurrent gross hematuria or microscopic hematuria, and pathological changes featuring poorly O-galactosylated IgA1 deposition in the glomerular mesangium. Pathogenesis has always been the focus of IgAN studies. After 50 years of research, most scholars agree that IgAN is a group of clinicopathological syndromes with certain common immunopathological characteristics, and multiple mechanisms are involved in its pathogenesis, including immunology, genetics, and environmental or nutritional factors. However, the precise pathogenetic mechanisms have not been fully determined. One hypothesis about the pathogenesis of IgAN suggests that immunological factors are engaged in all aspects of IgAN development and play a critical role. A variety of immune cells (e.g., dendritic cells, NK cells, macrophages, T-lymphocyte subsets, and B-lymphocytes, etc.) and molecules (e.g., IgA receptors, Toll-like receptors, complements, etc.) in innate and adaptive immunity are involved in the pathogenesis of IgAN. Moreover, the abnormality of mucosal immune regulation is the core of IgAN immunopathogenesis. The roles of tonsil immunity or intestinal mucosal immunity, which have received more attention in recent years, are supported by mounting evidence. In this review, we will explore the latest research insights on the role of immune modulation in the pathogenesis of IgAN. With a better understanding of immunopathogenesis of IgAN, emerging therapies will soon become realized.

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“…All tonsil stainings were performed on 4-µm paraffin sections as previously described [24]. In brief, immunofluorescence and immunohistochemical stains were performed on formalin-fixed, paraffin-embedded 4-µm sections.…”

Section: Methodsmentioning

confidence: 99%

Activation of the Interleukin-4/Signal Transducer and Activator of Transcription 6 Signaling Pathway and Homeodomain-Interacting Protein Kinase 2 Production by Tonsillar Mononuclear Cells in IgA Nephropathy

Peng²,

Liu³

et al. 2013

Am J Nephrol

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Background/Aim: Clinical development and exacerbation of IgA nephropathy (IgAN) are frequently preceded by episodes of upper respiratory tract infection such as tonsillitis. This study aimed to determine the role of the interleukin-4 (IL-4)/signal transducer and activator of transcription 6 (STAT6) signaling pathway and homeodomain-interacting protein kinase 2 (HIPK2) in aberrant IgA1 O-glycosylation production, and identify potential therapeutic targets in IgAN. Methods: Expression levels of IL-4, STAT6, core1β1,3-galactosyltransferase (C1GALT1C1), core1β3GalT-specific molecular chaperone (Cosmc) and HIPK2 in tonsil components were examined by immunohistochemical and immunofluorescence staining. Lymphocytes isolated from 22 patients with IgAN and 24 patients with chronic tonsillitis (CT) as controls were cultured for 72 h with or without IL-4, lipopolysaccharide (LPS) and α-hemolytic streptococcus (HS) stimulation. Expression levels of STAT6, C1GALT1C1, Cosmc, HIPK2-mRNA and protein were measured by real-time PCR and Western blot analysis, respectively. The concentration of IgA1 and level of O-glycosylation were determined by ELISA and Vicia villosa (VV) lectin-binding assay. To determine the contribution of HIPK2 in IgA secretion and O-glycosylation, cells were subjected to experiments for evaluation of HIPK2 silencing by Hipk2-siRNA transfection. Results: The IL-4/STAT6 signaling pathway was highly activated in all tonsil tissues (including the germinal center and tonsillar crypt epithelium) of IgAN patients, but the gene or protein expression of β1,3-Gal transferase (C1GALT1) and COSMC decreased significantly in patients with IgAN in comparison with those with CT. Hipk2 production in the tonsils derived from IgAN patients was significantly higher than that of CT patients. HIPK2-mRNA expression significantly negatively correlated with renal function as expressed by the estimated glomerular filtration rate, and also significantly positively correlated with daily proteinuria. The level of IL-4, STAT6 and HIPK2 were closely related with Lee's pathological grading system. The levels of mRNA and protein encoding STAT6 and Hipk2 in cells coincubated with IL-4, LPS and HS were significantly higher than those in the controls without stimulation; however, in the IgAN group the levels of mRNA and protein encoding C1GALT1 and Cosmc were significantly lower compared to the controls. IgA1 concentrations of supernatants in IgAN patients were remarkably higher under conditions of external stimulation. As expected, the optical density value of VV lectin binding to IgA1 increased after external stimulation in the IgAN group. By siRNA transfection, our results clearly indicate that Hipk2 negatively regulates C1GALT1 and Cosmc expression. Importantly, HIPK2-siRNA attenuates the aberrant glycosylation of IgA1 secretion. Conclusion: We identified and confirmed that activation of the IL-4/STAT6 signaling pathway has a crucial role in aberrant glycosylation of IgA1 secretion. HIPK2, a protein kinase previously unrecognized in kidney...

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Expression of CD19⁺CD5⁺B Cells and IgA1-positive cells in Tonsillar Tissues of IgA Nephropathy Patients

Abstract: The hallmark of IgA nephropathy (IgAN) is the mesangial deposits of polymeric IgA. However, the source of IgA1 and the mechanism of deposition of IgA1 in the mesangium remain unknown. To better understand its pathogenesis, we investigated the expression of CD19

Cited by 7 publications

References 21 publications

ST6Gal1 is up‐regulated and associated with aberrant IgA1 glycosylation in IgA nephropathy: An integrated analysis of the transcriptome

ST6Gal1 is up‐regulated and associated with aberrant IgA1 glycosylation in IgA nephropathy: An integrated analysis of the transcriptome

The Role of Immune Modulation in Pathogenesis of IgA Nephropathy

Activation of the Interleukin-4/Signal Transducer and Activator of Transcription 6 Signaling Pathway and Homeodomain-Interacting Protein Kinase 2 Production by Tonsillar Mononuclear Cells in IgA Nephropathy

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Expression of CD19+CD5+B Cells and IgA1-positive cells in Tonsillar Tissues of IgA Nephropathy Patients

Abstract: The hallmark of IgA nephropathy (IgAN) is the mesangial deposits of polymeric IgA. However, the source of IgA1 and the mechanism of deposition of IgA1 in the mesangium remain unknown. To better understand its pathogenesis, we investigated the expression of CD19

Cited by 7 publications

References 21 publications

ST6Gal1 is up‐regulated and associated with aberrant IgA1 glycosylation in IgA nephropathy: An integrated analysis of the transcriptome

ST6Gal1 is up‐regulated and associated with aberrant IgA1 glycosylation in IgA nephropathy: An integrated analysis of the transcriptome

The Role of Immune Modulation in Pathogenesis of IgA Nephropathy

Activation of the Interleukin-4/Signal Transducer and Activator of Transcription 6 Signaling Pathway and Homeodomain-Interacting Protein Kinase 2 Production by Tonsillar Mononuclear Cells in IgA Nephropathy

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Expression of CD19⁺CD5⁺B Cells and IgA1-positive cells in Tonsillar Tissues of IgA Nephropathy Patients