IgA Nephropathy and Related Diseases

Novák, Jan; Raška, Milan; Městecký, Jiří; Julian, Bruce A.

doi:10.1016/b978-0-12-415847-4.00105-1

Cited by 5 publications

(2 citation statements)

References 176 publications

(235 reference statements)

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“…It is now well accepted that the circulation of patients with IgAN contains immune complexes consisting of Gd-IgA1 [for reviews, see Ref. ( 61 , 180 )]. Initial analyses showed that Gd-IgA1 was predominantly in large-molecular-mass fractions of serum and was associated with IgG, thus indicating a possibility that Gd-IgA1 was bound by IgG in an immune complex ( 31 ).…”

Section: Immune Complexes Contain Galactose-deficient Iga1 In Iga Nepmentioning

confidence: 99%

“…Similarly, any approach that would block activation of mesangial cells by the pathogenic IgA1–IgG complexes would be desirable. Examples of such approaches are listed in Table 2 , and more details can be found in recent reviews ( 6 , 180 , 308 ). It is hoped that studies that discover the molecular defects of IgA1, the mechanisms of induction of the autoantibodies specific for Gd-IgA1, the composition and biological activities of the immune complexes, and the signaling pathways for activation of mesangial cells and glomerular injury will lead to disease-specific therapy.…”

Section: Treatmentmentioning

confidence: 99%

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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: Immune Complexes Contain Galactose-deficient Iga1 In Iga Nepmentioning

confidence: 99%

Section: Treatmentmentioning

confidence: 99%

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

et al. 2016

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Mucosal Immune Defense

Kaetzel¹

Encyclopedic Reference of Cancer

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Altered Expression of Lymphocyte Homing Chemokines in the Pathogenesis of IgA Nephropathy

Buren

Yamashita²,

Suzuki³

et al. 2007

IgA Nephropathy Today

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Defective adaptive humoral immune responses to mucosal immunogens, but intact systemic responses, are increasingly recognized in patients with IgA nephropathy (IgAN). Reduced expression of IgA+, J chain+ cells in the gut lamina propria, with collateral increases in these cells in the marrow, is also documented. Thus, there seems to be a derangement in a 'mucosa-marrow axis' in IgAN patients. Recent evidence indicates that chemokines regulate the localization of B cells and their progeny into respiratory and intestinal lamina propria, and into other lymphoid organs as well. Particularly, secretory epithelial cells express the chemokine CCL28, whereas small bowel cells uniquely express CCL25. Extramucosal sites preferentially express CXCL12, CXCL13 and/or CXCL16. Reciprocally, plasmablasts committed to IgA synthesis ubiquitously express the receptor (CCR10) for CCL28, and a subset also express the receptor (CCR9) for CCL25; neither of these is present on cells committed to IgG or IgM synthesis. Herein, the potential contributions of virally induced innate responses to defective mucosal immunity and overproduction of oligomeric IgA in the marrow and tonsils will be reviewed, particularly with respect to the influence that viral infection exerts upon the expression of selected chemokine and receptor pairs. The ramifications for pathogenesis of IgAN will be considered.

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IgA Nephropathy and Related Diseases

Cited by 5 publications

References 176 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

Mucosal Immune Defense

Altered Expression of Lymphocyte Homing Chemokines in the Pathogenesis of IgA Nephropathy

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