Identification and characterization of circulating immune complexes in IgA nephropathy.

Autor: 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.; Wyss Institute of Biologically Inspired Engineering, Harvard University, Boston, MA, USA., Wever WJ; Department of Surgery, Center for Drug Discovery and Translational Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.; Wyss Institute of Biologically Inspired Engineering, Harvard University, Boston, MA, USA., Lehoux S; Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA., Stavenhagen K; Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA., van Wijk JAE; Department of Pediatric Nephrology, Amsterdam University Medical Centre, location VUmc, Amsterdam, Netherlands., Van Die I; Department of Molecular Cell Biology and Immunology, Amsterdam University Medical Centre, Vrije Universiteit Amsterdam, Amsterdam, Netherlands., Chapman AB; Department of Medicine, Section of Nephrology, University of Chicago School of Medicine, Chicago, IL, USA., Chaikof EL; Department of Surgery, Center for Drug Discovery and Translational Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.; Wyss Institute of Biologically Inspired Engineering, Harvard University, Boston, MA, USA., Cummings RD; Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Jazyk: angličtina
Zdroj: Science advances [Sci Adv] 2022 Oct 28; Vol. 8 (43), pp. eabm8783. Date of Electronic Publication: 2022 Oct 28.
DOI: 10.1126/sciadv.abm8783
Abstrakt: 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.
Databáze: MEDLINE