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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...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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American Association for the Advancement of Science
2022
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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. |
format | Online Article Text |
id | pubmed-9616497 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Association for the Advancement of Science |
record_format | MEDLINE/PubMed |
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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