Pathogenesis of IgA Nephropathy: Current Understanding and Implications for Development of Disease-Specific Treatment

Knoppová, Barbora; Reily, Colin; King, R. Glenn; Julian, Bruce A.; Novák, Jan; Green, Todd

doi:10.3390/jcm10194501

Cited by 43 publications

(51 citation statements)

References 203 publications

(278 reference statements)

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“…This results in the change Neu5Acα2,6Gal-R HO in the structure of the IgA molecule, its impaired clearance by hepatocytes because the asialoglycoprotein receptor ASGPR, expressed on hepatocytes, recognizes the terminal residues of galactose and catabolizes IgA. Glycoforms of IgA1 are detected as selfantigens; this leads to the formation of circulating immune complexes, some of which are deposited in the glomeruli, causing kidney damage [68]. In many infectious diseases, changes in the pattern of total IgG glycosylation have been found in the blood.…”

Section: Sialic Acids Insulinmentioning

confidence: 99%

Clinical and Diagnostic Significance of Sialic Acids Determination in Biological Material

Vol'khina

Butolin

2022

Biochem. Moscow Suppl. Ser. B

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Sialic acids (SA) are neuraminic acid derivatives, located at the terminal position in the chains of monosaccharide residues of various glycoconjugates. SA play a dual role: they either mask recognition sites, or, on the contrary, represent biological targets that can be recognized by receptor proteins and serve as ligands. The desialylation/sialylation processes can be considered as a dynamic modification regulated by sialyltransferases and sialidases in response to external or internal stimuli. This review describes the structural and functional diversity and the potential use of SA fractions as biomarkers for various pathological conditions. Almost any extreme impact on the body and inflammatory processes are accompanied by an increase in the level of both total and free SA in the blood and tissues. Possible reasons for the increase of sialoglycoconjugate metabolism indicators in biological material include: (i) activation of the hepatocyte synthesis and secretion of various acute-phase proteins, many of which are sialoglycoproteins, (ii) impaired membrane integrity and destruction of body cells, (iii) high activity of sialidases (neurominidases) and sialyltransferases. Most acute and chronic liver diseases are characterized by the decrease in the total level of SA in the blood serum (because many plasma proteins are synthesized and glycosylated in hepatocytes). Aberrant sialylation results in changes of sialoglycoconjugate structure, its ability to perform biological functions and sialoglycoconjugate half-life. Glycosylation is the most common post-translational modification of proteins in the virus, which not only promotes the formation of specific conformation of viral proteins, but also modulates their interaction with receptors and affects host cell recognition, viral replication and infectivity. Serum total SA concentration increases in some benign and inflammatory conditions, which indicates a lack of specificity and limits their use for early detection and screening of neoplastic diseases. Clinical and diagnostic value of determining the sialoglycoconjugate metabolic indicators, including changes in the content of both SA fractions and specific proteins in various biological fluids and tissues, consists in establishing the causes and mechanisms of biochemical changes in the body in certain diseases. In combination with the measurement of existing markers, they can be used to improve diagnosis, staging and monitoring of therapeutic response in some pathological conditions where the need for specificity is less than for specific diagnostics.

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Section: Sialic Acids Insulinmentioning

confidence: 99%

Clinical and Diagnostic Significance of Sialic Acids Determination in Biological Material

Vol'khina

Butolin

2022

Biochem. Moscow Suppl. Ser. B

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“…Much progress has been made in defining the pathogenesis of this common form of GN [ 38 ]. A ‘four-hit’ pathogenic sequence is now fairly firmly established in primary IgAN [ 39 ].…”

Section: Deep Phenotyping/genotyping Of Patients With Gnmentioning

confidence: 99%

Precision medicine for the treatment of glomerulonephritis: a bold goal but not yet a transformative achievement

Glassock

2021

Clinical Kidney Journal

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The revolution in our ability to recognize the alterations in fundamental biology brought about by disease has fostered a renewed interest in precision or personalized medicine (“the right treatment, or diagnostic test, for the right patient at the right time”). This nascent field has been led by oncology, immune-hematology and infectious disease, but nephrology is catching up, and quickly. Specific forms of glomerulonephritis thought to represent specific “diseases” have been “downgraded” to “patterns of injury”. New entities have emerged through application of sophisticated molecular technologies; often embraced by the term “multi-omics”. Kidney biopsies are now interpreted by next generation imaging and machine learning. Many opportunities are manifest that will translate these remarkable developments into novel safe and effective treatment regimens for specific pathogenic pathways evoking glomerulonephritis and its progression to kidney failure. A few successes emboldens a positive look to the future. A sustained and highly collaborative engagement with this new paradigm will be required for this field, full of hope and high expectations, to realize its goal of transforming glomerular therapeutics from “one size fits all (or many)” to a true individualized management principle.

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“…Up to 40% of patients ultimately progress to end-stage kidney disease ( Selvaskandan et al., 2022 ). Although the underlying pathogenesis has not been completely elucidated, the “multi-hit-hypothesis” is a widely accepted immunological interpretation for IgAN, that is, the overproduction of polymeric Gd-IgA1, anti-Gd-IgA1 and the formation of circulating immune complex containing Gd-IgA1, the mesangial deposition of Gd-IgA1 immunocomplex, and subsequent inflammation and fibrosis ( Knoppova et al., 2021 ). Mesangial Gd-IgA1 deposits resemble mucosal IgA, mostly produced by mucosal B lymphocytes located in the Peyer’s patches, have been considered as an important pathogenetic factor of IgAN ( Ohyama et al., 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Gut Microbiome Characteristics in IgA Nephropathy: Qualitative and Quantitative Analysis from Observational Studies

Han

et al. 2022

Front. Cell. Infect. Microbiol.

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BackgroundRecent data indicate the importance of gut-kidney axis in the pathogenesis of Immunoglobulin A nephropathy (IgAN). Growing evidence suggests the alterations of diversity and composition of gut microbiome among patients with IgAN, however, the details are not yet fully understood.MethodsEligible studies comparing the gut microbiome between patients with IgAN and non-IgAN individuals were systematically searched from PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure, and ClinicalTrials.gov. The primary outcomes were alpha- and beta-diversity, and the differences in gut microbiota composition between patients with IgAN and non-IgAN persons. Qualitative analysis and meta-analysis were performed according to available data.ResultsEleven cross-sectional studies, including 409 patients with IgAN and 243 healthy controls, were enrolled. No significant differences in the diversity and enrichment of gut bacteria were found between IgAN and healthy individuals, whereas the beta-diversity consistently showed significant microbial dissimilarities among the two groups. Firmicutes, Bacteroidetes, Actinobacteria, Proteobacteria, Fusobacteria, and Verrucomicrobia were the dominant phyla, however, no significant differences were found between IgAN patients and healthy controls at the phylum level. The genera, Streptococcus and Paraprevotella showed a higher proportion in patients with IgAN compared to healthy individuals, whereas Fusicatenibacter showed a lower abundance according to meta-analysis. Qualitative analyses suggested that Escherichia-Shigella might be increased in IgAN patients; the genera, Clostridium, Prevotella 9,and Roseburia, members of Ruminococcaceae and Lachnospiraceae families, were likely to have decreased abundances in patients with IgAN compared to healthy individuals.ConclusionGut microbiota dysbiosis was demonstrated in IgAN, which might be involved in the pathogenesis of IgAN. Further studies are needed to confirm the findings of this study, due to the substantial heterogeneity.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, identifier PROSPERO (CRD42022304034).

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Pathogenesis of IgA Nephropathy: Current Understanding and Implications for Development of Disease-Specific Treatment

Cited by 43 publications

References 203 publications

Clinical and Diagnostic Significance of Sialic Acids Determination in Biological Material

Clinical and Diagnostic Significance of Sialic Acids Determination in Biological Material

Precision medicine for the treatment of glomerulonephritis: a bold goal but not yet a transformative achievement

Gut Microbiome Characteristics in IgA Nephropathy: Qualitative and Quantitative Analysis from Observational Studies

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