New insights into the pathogenesis of IgA nephropathy: do toll like receptor 9-B cell activation factor-IgA class switching recombination signaling axis induce IgA hyper-production?

Liu, Yuyuan; Liu, Hong; Peng, Youming; Liu, Fuyou

doi:10.3109/0886022x.2014.916578

Cited by 5 publications

(7 citation statements)

References 31 publications

(32 reference statements)

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“…BAFF has been recognized as a biomarker that is associated with clinical and histopathological features [43] . In our previous studies, we revealed that high levels of BAFF can promote IgA CSR and the secretion of aberrantly glycosylated IgA1 [20,26,44] . TLR3-BAFF axis, first mentioned in the field rheumatoid arthritis, has supported in vivo that TLR3-BAFF can induce AID expression and Ig class-switching in B cells [45,46] .…”

Section: Discussionmentioning

confidence: 99%

“…Recently, we focused on the role of IgA CSR in the pathogenesis of IgAN and hold the opinion that TLR9-BAFF pathway-induced IgA CSR may be of great significance for pathogenesis of IgAN elucidates and IgAN treatment [20] . IgA is the predominant immunoglobulin (Ig) isotype in mucosal secretions and serves as a first line of defense in the mucosa by inhibiting pathogen adhesion.…”

Section: Introductionmentioning

confidence: 99%

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Synthetic Double-Stranded RNA Poly(I:C) Aggravates IgA Nephropathy by Triggering IgA Class Switching Recombination through the TLR3-BAFF Axis

He¹,

Peng²,

Wang³

et al. 2015

Am J Nephrol

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Background: Immunoglobulin class-switch recombination (CSR) is crucial for the expression of IgA, and it plays a vital role in the physiopathology of IgA nephropathy (IgAN). The aim of the study is to investigate the effect of polyriboinosinic:polyribocytidylic acid (poly(I:C)) in modulating toll-like receptor (TLR) 3-B-cell-activating factor belonging to the TNF family (BAFF) axis activation, which in turn promotes IgA CSR of IgAN patients and the IgAN rat model. Methods: Blood samples and tonsillar tissue specimens were obtained from 24 patients with IgAN and 26 patients with chronic tonsillitis as control. We also used the IgAN rat model to investigate the relationship between viral infection and IgA CSR. Results: Immunohistochemical and ELISA western blotting examination revealed that the TLR3/BAFF axis is activated in IgAN patients when compared to controls. Synthetic double-stranded RNA poly(I:C) stimulation upregulates the TACI/TLR3/TRIF/TRAF6 expression and promotes IgA CSR and BAFF productions in tonsil mononuclear cells. TLR3 or BAFF siRNA decreases IgA expression. In IgAN rat models, TLR3/BAFF signaling was highly activated. With 200 μg poly(I:C) sodium salt into the left naris for 8 weeks, IgA was highly deposited on glomeruli. It also revealed that poly(I:C) activated TLR3/BAFF axis and IgA CSR in vivo. Conclusion: These data points toward the role of TLR3/BAFF axis in IgA CSR of IgAN, and the data also support the notion that mucosal immunization with virus infection results in impaired mucosal and systemic IgA responses.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Synthetic Double-Stranded RNA Poly(I:C) Aggravates IgA Nephropathy by Triggering IgA Class Switching Recombination through the TLR3-BAFF Axis

He¹,

Peng²,

Wang³

et al. 2015

Am J Nephrol

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“…Besides the abovementioned T-cell-depended IgA class switching, the T-cell-independent manners of IgA switching may be involved in the intensive production of IgA and Gd-IgA1 in IgAN patients. This kind of IgA switching is mediated through molecules such as tumor necrosis factor ligand superfamily members 13 [59] and 13b [60, 61] (called April and BAFF, respectively) which are important for B cell development. Authors found out that serum levels of April and BAFF were increased in IgAN patients [59, 60].…”

Section: Elevated Synthesis Of Gd-iga1—the Role Of Th2 Th17 and Tfh-mentioning

confidence: 99%

T cells in IgA nephropathy: role in pathogenesis, clinical significance and potential therapeutic target

et al. 2018

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Background Immunoglobulin A nephropathy (IgAN), the most frequent cause of primary glomerulonephritis worldwide, is an autoimmune disease with complex pathogenesis. In this review, we focus on T cells and summarize knowledge about their involvement in pathophysiology and treatment of IgAN Methods We reviewed the literature for (1) alterations of T cell subpopulations in IgAN, (2) experimental and clinical proofs for T cells’ participation in IgAN pathogenesis, (3) clinical correlations with T cell-associated alterations, and (4) influence of drugs used in IgAN therapy on T cell subpopulations. Results We found that IgAN is characterized by higher proportions of circulatory Th2, Tfh, Th17, Th22 and γδ T cells, but lower Th1 and Treg cells. We discuss genetic and epigenetic makeup that may contribute to this immunological phenotype. We found that Th2, Th17 and Tfh-type interleukins contribute to elevated synthesis of galactose-deficient IgA1 (Gd-IgA1) and that the production of anti-Gd-IgA1 autoantibodies may be stimulated by Tfh cells. We described the roles of Th2, Th17, Th22 and Treg cells in the renal injury and summarized correlations between T cell-associated alterations and clinical features of IgAN (proteinuria, reduced GFR, hematuria). We detailed the impact of immunosuppressive drugs on T cell subpopulations and found that the majority of drugs have nonoptimal influence on T cells in IgAN patients. Conclusions T cells play an important role in IgAN pathogenesis and are correlated with its clinical severity. Clinical trials with the drugs targeting the reported alterations of the T-cell compartment are highly desirable.

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“…Aberrant APRIL expression in tonsillar germinal centers correlated with greater proteinuria and responded well to tonsillectomy with decreases in serum levels of galactose-deficient IgA1 in patients with IgAN (8). It was hypothesized that in patients with IgAN, a TLR 9-BAFF (B cell activation factor)-IgA axis may exist that can enhance IgA production (9). It was suggested that overexpression of TLR 9 mRNA and protein in PBMCs and elevated levels of serum BAFF maybe associated with overexpression of serum IgA1 and could have a role in the development of IgAN (10).…”

Section: Discussionmentioning

confidence: 99%

“…TLR activation may enhance the synthesis of IgA and alter IgA glycosylation. Upregulation of TLRs has been reported in peripheral-blood mononuclear cells (PBMCs) of patients with IgAN (8,9,10). However, TLR renal expression was not systematically studied in IgAN (11).…”

Section: Introductionmentioning

confidence: 99%

Does the renal expression of Toll-like receptors play a role in patients with IgA nephropathy?

et al. 2019

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The onset of IgA nephropathy (IgAN), characterized by glomerular deposition of IgA-containing immune complexes, is often associated with synpharyngitic hematuria. Innate immune responses mediated by Toll-like receptors (TLR) may play a role in IgAN onset and/or progression. Here, we assessed the expression of TLR 4, 7, 8, and 9 in renal-biopsy specimens from patients with IgAN, with different degree of proteinuria and eGFR, compared with normal-kidney and disease-control tissues (ANCA-associated vasculitis). Renal-biopsy specimens from 34 patients with IgAN and 7 patients with ANCA-associated vasculitis were used. In addition, we used 15 healthy portions of renal-tissue specimens from kidneys after nephrectomy for cancer as control specimens.

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New insights into the pathogenesis of IgA nephropathy: do toll like receptor 9-B cell activation factor-IgA class switching recombination signaling axis induce IgA hyper-production?

Abstract: IgA nephropathy (IgAN)

Cited by 5 publications

References 31 publications

Synthetic Double-Stranded RNA Poly(I:C) Aggravates IgA Nephropathy by Triggering IgA Class Switching Recombination through the TLR3-BAFF Axis

Synthetic Double-Stranded RNA Poly(I:C) Aggravates IgA Nephropathy by Triggering IgA Class Switching Recombination through the TLR3-BAFF Axis

T cells in IgA nephropathy: role in pathogenesis, clinical significance and potential therapeutic target

Does the renal expression of Toll-like receptors play a role in patients with IgA nephropathy?

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