Published October 28, 2022
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Identification and characterization of circulating immune complexes in IgA nephropathy
Creators
- 1. Harvard University
- 2. Amsterdam University Medical Centre
- 3. University of Chicago
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.
Data availability
All data needed to evaluate the conclusions in the paper are present in the paper and/or Supplementary Materials with no restrictions. The DiαGalNAc can be provided by E.L.C. pending scientific review and a completed material transfer agreement. Requests for the DiαGalNAc should be submitted to echaikof@bidmc.harvard.edu.
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Additional details
Identifiers
- DOI
- 10.1126/sciadv.abm8783
- Other
- oai:uchicago.tind.io:10917
Funding
- National Institute of General Medical Sciences
- P41GM103694
- National Institute of General Medical Sciences
- R24GM137763
- National Institute of Diabetes and Digestive and Kidney Diseases
- R01DK080876