2023
DOI: 10.3389/fimmu.2023.1165394
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Current understanding of IgA antibodies in the pathogenesis of IgA nephropathy

Abstract: Immunoglobulin A (IgA) is the most abundant isotype of antibodies, provides a first line of defense at mucosal surfaces against pathogens, and thereby contributes to mucosal homeostasis. IgA is generally considered as a non-inflammatory antibody because of its main function, neutralizing pathogenic virus or bacteria. Meanwhile, IgA can induce IgA-mediated diseases, such as IgA nephropathy (IgAN) and IgA vasculitis. IgAN is characterized by the deposition of IgA and complement C3, often with IgG and/or IgM, in … Show more

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Cited by 24 publications
(13 citation statements)
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References 69 publications
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“…Currently, experiments have detected C5, C6, C9, and MAC in kidney biopsy tissue, providing further evidence for the explanation and rationality of this phenomenon. IgAN is characterized by the deposition of IgA and complement C3, often with IgG and/or IgM, in the glomerular mesangial region, followed by mesangial-cell proliferation and extreme synthesis of extracellular matrix in glomeruli [ 21 ]. What is more, IgAN is described by mesangial deposits of IgA1-containing immune complexes.…”
Section: Discussionmentioning
confidence: 99%
“…Currently, experiments have detected C5, C6, C9, and MAC in kidney biopsy tissue, providing further evidence for the explanation and rationality of this phenomenon. IgAN is characterized by the deposition of IgA and complement C3, often with IgG and/or IgM, in the glomerular mesangial region, followed by mesangial-cell proliferation and extreme synthesis of extracellular matrix in glomeruli [ 21 ]. What is more, IgAN is described by mesangial deposits of IgA1-containing immune complexes.…”
Section: Discussionmentioning
confidence: 99%
“…In the final stage of pathogenesis, mesangial deposition of circulating Gd-IgA1-antiglycan IgG immune complex in the renal allograft results in cell activation and glomerular injury, ultimately leads to recurrence. Transferrin receptor 1 (TfR1) was identified as an IgA1 receptor expressed on human mesangial cells and has affinity with the immune complex formed by Gd-IgA1 and IgG ( 85 ). Our observation that related donors and patients with low HLA mismatch are more likely to recur may indicate that allografts with similar genetic backgrounds may express more IgA1 receptors and therefore have higher affinity for host circulating immune complexes.…”
Section: Discussionmentioning
confidence: 99%
“…It has been hypothesized that in patients with IgAN, altered homing leads to mucosally-derived IgA + plasma cells being mis-trafficked to systemic sites, such as the bone marrow, resulting in the production of “mucosal-type” Gd-IgA1 in the circulation ( 54 56 ). Other recent work has highlighted possible roles for reverse transcytosis of Gd-IgA1 from the gut lumen, or trafficking of IgA + B cells to the kidneys in the pathogenesis of IgAN ( 57 , 58 ).…”
Section: Pathogenesis and The Four-hit Hypothesismentioning
confidence: 99%