Identification and characterization of circulating immune complexes in IgA nephropathy

The underlying pathology of immunoglobulin A (IgA) nephropathy (IgAN), the most common glomerulonephritis worldwide, is driven by the deposition of immune complexes containing galactose-deficient IgA1 [Tn(+)IgA1] in the glomerular mesangium. Here, we report that novel anti-Tn circulating immune comp...

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Veröffentlicht in:Science advances 2022-10, Vol.8 (43), p.eabm8783-eabm8783
Hauptverfasser: Matsumoto, Yasuyuki, Aryal, Rajindra P, Heimburg-Molinaro, Jamie, Park, Simon S, Wever, Walter J, Lehoux, Sylvain, Stavenhagen, Kathrin, van Wijk, Joanna A E, Van Die, Irma, Chapman, Arlene B, Chaikof, Elliot L, Cummings, Richard D
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Sprache:eng
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Zusammenfassung:The underlying pathology of immunoglobulin A (IgA) nephropathy (IgAN), the most common glomerulonephritis worldwide, is driven by the deposition of immune complexes containing galactose-deficient IgA1 [Tn(+)IgA1] in the glomerular mesangium. Here, we report that novel anti-Tn circulating immune complexes (anti-Tn CICs) contain predominantly IgM, representing large macromolecular complexes of ~1.2 megadaltons to several megadalton sizes together with Tn(+)IgA1 and some IgG. These complexes are significantly elevated in sera of patients with IgAN, which contains higher levels of complement C3, compared to healthy individuals. Anti-Tn CICs are bioactive and induce specific proliferation of human renal mesangial cells. We found that these anti-Tn CICs can be dissociated with small glycomimetic compounds, which mimic the Tn antigen of Tn(+)IgA1, releasing IgA1 from anti-Tn CICs. This glycomimetic compound can also significantly inhibit the proliferative activity of anti-Tn CICs of patients with IgAN. These findings could enhance both the diagnosis of IgAN and its treatment, as specific drug treatments are now unavailable.
ISSN:2375-2548
2375-2548
DOI:10.1126/sciadv.abm8783