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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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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9616497/
https://www.ncbi.nlm.nih.gov/pubmed/36306365
http://dx.doi.org/10.1126/sciadv.abm8783
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author 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.
author_facet 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.
author_sort Matsumoto, Yasuyuki
collection PubMed
description 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.
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spelling pubmed-96164972022-11-04 Identification and characterization of circulating immune complexes in IgA nephropathy 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. Sci Adv Biomedicine and Life Sciences 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. American Association for the Advancement of Science 2022-10-28 /pmc/articles/PMC9616497/ /pubmed/36306365 http://dx.doi.org/10.1126/sciadv.abm8783 Text en Copyright © 2022 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). https://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (https://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.
spellingShingle Biomedicine and Life Sciences
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.
Identification and characterization of circulating immune complexes in IgA nephropathy
title Identification and characterization of circulating immune complexes in IgA nephropathy
title_full Identification and characterization of circulating immune complexes in IgA nephropathy
title_fullStr Identification and characterization of circulating immune complexes in IgA nephropathy
title_full_unstemmed Identification and characterization of circulating immune complexes in IgA nephropathy
title_short Identification and characterization of circulating immune complexes in IgA nephropathy
title_sort identification and characterization of circulating immune complexes in iga nephropathy
topic Biomedicine and Life Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9616497/
https://www.ncbi.nlm.nih.gov/pubmed/36306365
http://dx.doi.org/10.1126/sciadv.abm8783
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