Immune complex formation in IgA nephropathy: CD89 a ‘saint’ or a ‘sinner’?

Boyd, Joanna; Barratt, Jonathan

doi:10.1038/ki.2010.365

Cited by 29 publications

(28 citation statements)

References 11 publications

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“…These transgenic mice develop mesangial IgA deposits, glomerular and interstitial macrophage infiltration, mesangial matrix expansion, hematuria, and mild proteinuria. However, follow-up studies have raised questions whether CD89 is involved in a similar manner in human IgAN, as mice do not have a homolog of human CD89 ( 266 , 267 ).…”

Section: Animal Modelsmentioning

confidence: 99%

The Origin and Activities of IgA1-Containing Immune Complexes in IgA Nephropathy

et al. 2016

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IgA nephropathy (IgAN) is the most common primary glomerulonephritis, frequently leading to end-stage renal disease, as there is no disease-specific therapy. IgAN is diagnosed from pathological assessment of a renal biopsy specimen based on predominant or codominant IgA-containing immunodeposits, usually with complement C3 co-deposits and with variable presence of IgG and/or IgM. The IgA in these renal deposits is galactose-deficient IgA1, with less than a full complement of galactose residues on the O -glycans in the hinge region of the heavy chains. Research from the past decade led to the definition of IgAN as an autoimmune disease with a multi-hit pathogenetic process with contributing genetic and environmental components. In this process, circulating galactose-deficient IgA1 (autoantigen) is bound by antiglycan IgG or IgA (autoantibodies) to form immune complexes. Some of these circulating complexes deposit in glomeruli, and thereby activate mesangial cells and induce renal injury through cellular proliferation and overproduction of extracellular matrix components and cytokines/chemokines. Glycosylation pathways associated with production of the autoantigen and the unique characteristics of the corresponding autoantibodies in patients with IgAN have been uncovered. Complement likely plays a significant role in the formation and the nephritogenic activities of these complexes. Complement activation is mediated through the alternative and lectin pathways and probably occurs systemically on IgA1-containing circulating immune complexes as well as locally in glomeruli. Incidence of IgAN varies greatly by geographical location; the disease is rare in central Africa but accounts for up to 40% of native-kidney biopsies in eastern Asia. Some of this variation may be explained by genetically determined influences on the pathogenesis of the disease. Genome-wide association studies to date have identified several loci associated with IgAN. Some of these loci are associated with the increased prevalence of IgAN, whereas others, such as deletion of complement factor H-related genes 1 and 3, are protective against the disease. Understanding the molecular mechanisms and genetic and biochemical factors involved in formation and activities of pathogenic IgA1-containing immune complexes will enable the development of future disease-specific therapies as well as identification of non-invasive disease-specific biomarkers.

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Section: Animal Modelsmentioning

confidence: 99%

The Origin and Activities of IgA1-Containing Immune Complexes in IgA Nephropathy

et al. 2016

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“…As a consequence, cleavage of the extracellular domain of FcaRI is induced, leading to the formation of circulating IgA/FcaRI immune complexes, which are found in mesangial deposits. IgA/FcaRI immune complexes have been implicated in disease exacerbation through the release of pro-inflammatory cytokines, secretion of chemokines and the resultant migration of macrophages into the kidney [40,[89][90][91].…”

Section: Anti-glycan Antibodies and Immune Complexesmentioning

confidence: 99%

Immunoglobulin A nephropathy: a pathophysiology view

2016

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“…Although IgA-IC formation is thought to be universal in IgAN, clinical features, biopsy findings, and disease progression are highly variable. Patients in whom IgAN runs a benign course, the non progressors (NP), cannot currently be identified from progressors (P) at diagnosis [9]. Recently, IgAN patients were classified as non progressor (NP) when they fulfilled both the following criteria: (i) decrease, after at least 6 months, in daily proteinuria 50% of the value recorded at the start of therapy with Angiotensin-converting enzyme inhibitors (ACEi) treatment; and (ii) stable glomerular filtration rate throughout ACEi treatment [10], [11].…”

Section: Introductionmentioning

confidence: 99%

Microbiota and Metabolome Associated with Immunoglobulin A Nephropathy (IgAN)

et al. 2014

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This study aimed at investigating the fecal microbiota, and the fecal and urinary metabolome of non progressor (NP) and progressor (P) patients with immunoglobulin A nephropathy (IgAN). Three groups of volunteers were included in the study: (i) sixteen IgAN NP patients; (ii) sixteen IgAN P patients; and (iii) sixteen healthy control (HC) subjects, without known diseases. Selective media were used to determine the main cultivable bacterial groups. Bacterial tag-encoded FLX-titanium amplicon pyrosequencing of the 16S rDNA and 16S rRNA was carried out to determine total and metabolically active bacteria, respectively. Biochrom 30 series amino acid analyzer and gas-chromatography mass spectrometry/solid-phase microextraction (GC-MS/SPME) analyses were mainly carried out for metabolomic analyses. As estimated by rarefaction, Chao and Shannon diversity index, the lowest microbial diversity was found in P patients. Firmicutes increased in the fecal samples of NP and, especially, P patients due to the higher percentages of some genera/species of Ruminococcaceae, Lachnospiraceae, Eubacteriaceae and Streptococcaeae. With a few exceptions, species of Clostridium, Enterococcus and Lactobacillus genera were found at the highest levels in HC. Bacteroidaceae, Porphyromonadaceae, Prevotellaceae and Rikenellaceae families differed among NP, P and HC subjects. Sutterellaceae and Enterobacteriaceae species were almost the highest in the fecal samples of NP and/or P patients. Compared to HC subjects, Bifidobacterium species decreased in the fecal samples of NP and P. As shown by multivariate statistical analyses, the levels of metabolites (free amino acids and organic volatile compounds) from fecal and urinary samples markedly differentiated NP and, especially, P patients.

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Immune complex formation in IgA nephropathy: CD89 a ‘saint’ or a ‘sinner’?

Cited by 29 publications

References 11 publications

The Origin and Activities of IgA1-Containing Immune Complexes in IgA Nephropathy

The Origin and Activities of IgA1-Containing Immune Complexes in IgA Nephropathy

Immunoglobulin A nephropathy: a pathophysiology view

Microbiota and Metabolome Associated with Immunoglobulin A Nephropathy (IgAN)

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