Aberrantly Glycosylated IgA1 as a Factor in the Pathogenesis of IgA Nephropathy

Tanaka, Mototsugu; Seki, George; Someya, Tomonosuke; Nagata, Michio; Fujita, Toshiro

doi:10.1155/2011/470803

Cited by 22 publications

(18 citation statements)

References 58 publications

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“…Recent proteomic studies indicate that the number of glycoproteins contributing to the lectin profiles we observed is likely to be high [7], [16], [19], [53]. Variations of the glycosylation of individual proteins has been associated with kidney diseases and metabolic disorders which affect kidney function such as those in hinge-region, O -linked glycosylation associated with IgA-mediated nephropathies [54], [55] and podocyte flattening suggested to be dependent upon incorrect glycosylation of alpha-dystroglycan [56]. Whether specific glycoproteins that are enriched in uEVs manifest altered oligosaccharide composition during kidney disease will require further investigation.…”

Section: Discussionmentioning

confidence: 90%

Surface Glycosylation Profiles of Urine Extracellular Vesicles

et al. 2013

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Urinary extracellular vesicles (uEVs) are released by cells throughout the nephron and contain biomolecules from their cells of origin. Although uEV-associated proteins and RNA have been studied in detail, little information exists regarding uEV glycosylation characteristics. Surface glycosylation profiling by flow cytometry and lectin microarray was applied to uEVs enriched from urine of healthy adults by ultracentrifugation and centrifugal filtration. The carbohydrate specificity of lectin microarray profiles was confirmed by competitive sugar inhibition and carbohydrate-specific enzyme hydrolysis. Glycosylation profiles of uEVs and purified Tamm Horsfall protein were compared. In both flow cytometry and lectin microarray assays, uEVs demonstrated surface binding, at low to moderate intensities, of a broad range of lectins whether prepared by ultracentrifugation or centrifugal filtration. In general, ultracentrifugation-prepared uEVs demonstrated higher lectin binding intensities than centrifugal filtration-prepared uEVs consistent with lesser amounts of co-purified non-vesicular proteins. The surface glycosylation profiles of uEVs showed little inter-individual variation and were distinct from those of Tamm Horsfall protein, which bound a limited number of lectins. In a pilot study, lectin microarray was used to compare uEVs from individuals with autosomal dominant polycystic kidney disease to those of age-matched controls. The lectin microarray profiles of polycystic kidney disease and healthy uEVs showed differences in binding intensity of 6/43 lectins. Our results reveal a complex surface glycosylation profile of uEVs that is accessible to lectin-based analysis following multiple uEV enrichment techniques, is distinct from co-purified Tamm Horsfall protein and may demonstrate disease-specific modifications.

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Section: Discussionmentioning

confidence: 90%

Surface Glycosylation Profiles of Urine Extracellular Vesicles

et al. 2013

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“…Although the pathogenesis of IgAN is incompletely understood, yet the qualitative abnormality of IgA molecules is now recognized as a fundamental cause of developing IgAN [32] . This study, for the first time, clarified that synthetic double-stranded RNA poly(I:C) regulates TLR3/BAFF signaling to enhance IgA CSR in IgAN patients and in the IgAN rat model.…”

Section: Discussionmentioning

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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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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“…The glycosylation state of IgA is reported to modulate interaction with Fc␣ receptors of phagocytic cells and to participate in anchoring of SIgA and bound antigen in the mucus layer (42,43). Many different glycoforms of SIgA have been documented and are sometimes associated with specific disease states (44). However, in comparison with other mucosal surfaces, the roles of SIgA in the reproductive tract are not well understood.…”

Section: Bacterial Vaginosis (Bv)mentioning

confidence: 99%

Hydrolysis of Secreted Sialoglycoprotein Immunoglobulin A (IgA) in ex Vivo and Biochemical Models of Bacterial Vaginosis

Lewis

Robinson

Perry

et al. 2012

Journal of Biological Chemistry

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Background: Sialidase activity is a key feature of bacterial vaginosis (BV), but possible substrates have not undergone in-depth investigation. Results: We show that sialidase activity in BV clinical specimens removes sialic acids from secretory immunoglobulin A (SIgA) and other sialoglycans. Conclusion: Desialylation of SIgA promotes further exodeglycosylation and proteolysis. Significance: Hydrolysis of SIgA and other sialoglycans may contribute to the etiology of BV.

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Aberrantly Glycosylated IgA1 as a Factor in the Pathogenesis of IgA Nephropathy

Cited by 22 publications

References 58 publications

Surface Glycosylation Profiles of Urine Extracellular Vesicles

Surface Glycosylation Profiles of Urine Extracellular Vesicles

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

Hydrolysis of Secreted Sialoglycoprotein Immunoglobulin A (IgA) in ex Vivo and Biochemical Models of Bacterial Vaginosis

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