Characterisation of B cells responsible for anti-Gd-IgA autoantibody production from peripheral blood of IgAN patients 2910

Abstract Description IgA nephropathy (IgAN) is glomerulonephritis characterized by deposition of immune complexes (IC) in kidneys.IC consist of IgA1 with aberrant O-glycans in hinge region (Gd-IgA1) and Gd-IgA1- autoantibody.Although Gd-IgA1+ cells in peripheral blood were described,Anti–Gd-IgA1+ cells are still uncharacterized.Here,we describe,for the first time,Anti-Gd-IgA+ B cells in peripheral blood of 5 IgAN patients and 5 healthy controls.For Anti-Gd-IgA1 cell detection recombinant fragment of IgA1 consisting of first constant region of heavy chain,hinge region and second constant region (CH1-HR-CH2) was produced,GalNAc-cosylated and conjugated with DyLight405.Cells were stained for CD19,IgA,CD38 and CH1-HR-CH2-DyLight405 and analysed by flow cytometry.Our results show that 0.5% of all CD19 cells are Anti-Gd-IgA1 cells,with 20% of IgA and 80% of IgG isotype.15% of anti-Gd-IgA1 cells are CD38+ indicating plasmablast phenotype.No significant differences were detected between IgAN and HC groups.Here,we characterized B cells that represent potential precursors of Anti-Gd-IgA1 autoantibody producing cells which could play crucial role in IgAN.Nevertheless,further aspects need to be investigated,such as different cytokine impact on Anti-Gd-IgA1 cells terminal differentiation,intensity of autoantibody production and their affinity.Deeper characterisation of these cells will help us to understand the IgAN ethiopathogenesis and may help to find targets for efficient therapeutic intervention. Funding Sources Supported by MZ CR – RVO (FNOL, 00098892) Topic Categories Basic Autoimmunity (BA)