Identification and characterization of circulating immune complexes in IgA nephropathy-Reference-Cited by-同舟云学术

Identification and characterization of circulating immune complexes in IgA nephropathy

Published:2022-10-28 Issue:43 Volume:8 Page:
ISSN:2375-2548
Container-title:Science Advances
language:en
Short-container-title:Sci. Adv.

Author:

Matsumoto Yasuyuki¹^ORCID,Aryal Rajindra P.¹^ORCID,Heimburg-Molinaro Jamie¹^ORCID,Park Simon S.²³^ORCID,Wever Walter J.²³^ORCID,Lehoux Sylvain¹,Stavenhagen Kathrin¹^ORCID,van Wijk Joanna A. E.⁴^ORCID,Van Die Irma⁵^ORCID,Chapman Arlene B.⁶^ORCID,Chaikof Elliot L.²³^ORCID,Cummings Richard D.¹^ORCID

Affiliation:

1. Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.

2. Department of Surgery, Center for Drug Discovery and Translational Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.

3. Wyss Institute of Biologically Inspired Engineering, Harvard University, Boston, MA, USA.

4. Department of Pediatric Nephrology, Amsterdam University Medical Centre, location VUmc, Amsterdam, Netherlands.

5. Department of Molecular Cell Biology and Immunology, Amsterdam University Medical Centre, Vrije Universiteit Amsterdam, Amsterdam, Netherlands.

6. Department of Medicine, Section of Nephrology, University of Chicago School of Medicine, Chicago, IL, USA.

Abstract

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.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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