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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.
Afiliação
  • Matsumoto Y; Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
  • Aryal RP; Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
  • Heimburg-Molinaro J; Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
  • Park SS; Department of Surgery, Center for Drug Discovery and Translational Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
  • Wever WJ; Wyss Institute of Biologically Inspired Engineering, Harvard University, Boston, MA, USA.
  • Lehoux S; Department of Surgery, Center for Drug Discovery and Translational Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
  • Stavenhagen K; Wyss Institute of Biologically Inspired Engineering, Harvard University, Boston, MA, USA.
  • van Wijk JAE; Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
  • Van Die I; Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
  • Chapman AB; Department of Pediatric Nephrology, Amsterdam University Medical Centre, location VUmc, Amsterdam, Netherlands.
  • Chaikof EL; Department of Molecular Cell Biology and Immunology, Amsterdam University Medical Centre, Vrije Universiteit Amsterdam, Amsterdam, Netherlands.
  • Cummings RD; Department of Medicine, Section of Nephrology, University of Chicago School of Medicine, Chicago, IL, USA.
Sci Adv ; 8(43): eabm8783, 2022 10 28.
Article em En | MEDLINE | ID: mdl-36306365
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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Glomerulonefrite por IGA Idioma: En Ano de publicação: 2022 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Glomerulonefrite por IGA Idioma: En Ano de publicação: 2022 Tipo de documento: Article