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During the congress, E-Posters will be accessible to all participants on the congress website 24/7, as well as in the E-poster stations in the congress center.
Preparing your E-Poster
Please review the E-Poster format requirements carefully when preparing your E-Poster. Should your E-Poster not meet the mentioned requirements, it may not be displayed as described above.
E-Poster Submission Deadline
Please prepare and upload your E-Poster no later than March 14, 2026 11.59PM CET. After this date, you will no longer be able to prepare and upload your E-poster and it will not be displayed and accessible on the congress website.
Please follow the instructions below to input your abstract title.
Abstract titles should be brief and reflect the content of the abstract.
IgA nephropathy (IgAN) is characterized by glomerular immune-complex deposits containing IgA1 with some hinge-region O-glycans lacking galactose (galactose-deficient IgA1; Gd-IgA1). Gd-IgA1, likely produced by mucosal IgA-secreting cell, is recognized by IgG autoantibodies to form nephritogenic immune complexes in the circulation. Gd-IgA1-secreting cells exhibit reduced expression of C1GALT1, a galactosyltransferase, and its molecular chaperone C1GALT1C1. Furthermore, dysregulated expression of GALNT14, one of the enzymes initiating O-glycosylation, impacts homing phenotype of B cells, thereby affecting circulation and localization of IgA-producing cells. However, regulation of these glycosyltransferases remains unclear. As tonsillectomy has shown clinical efficacy in Japanese patients with IgAN, analysis of primary tonsillar IgA+ cells offers an opportunity for elucidating disease pathogenesis. Based on in vitro analyses using IgA1-producing cell lines, we focused on B-cell receptor (BCR) signaling. Our findings suggest that Bruton’s tyrosine kinase (Btk), a key component of BCR signaling, modulates expression of glycosyltransferases involved in O-glycosylation pathways.
Immortalized IgA1-producing cell lines derived from peripheral blood of IgAN patients and healthy controls (HC) were treated with a Btk inhibitor (ibrutinib). Gd-IgA1 production was determined by lectin ELISA. Intracellular signaling was assessed by immunoblotting using phospho-Btk-specific antibody. Using primary tonsillar mononuclear cells (TMNCs) from patients with IgAN or chronic tonsillitis (disease controls; DC), phospho-Btk in B-cell subsets was analyzed by flow cytometry. IgA+ and IgD+ TMNCs were isolated and cultured to analyze expression of O-glycosyltransferases C1GALT1, C1GALT1C1, GALNT2, and GALNT14 by qPCR. IgA+ TMNCs were incubated with an anti-IgA antibody (BCR activation) or ibrutinib (Btk inhibition), and the expression of these glycosyltransferases was quantified.
IgA1-producing cell lines from IgAN patients secreted more Gd-IgA1 than those from HC (p<0.01). Ibrutinib reduced Gd-IgA1 production more in IgAN-derived than HC-derived cells (p<0.01). Immunoblotting revealed elevated phospho-Btk in IgAN-derived cells (p<0.05). In TMNCs, elevated phospho-Btk levels were detected in CD38+ germinal-center (GC) and pre-GC B cells from IgAN patients (p=0.017). In IgAN- vs. DC-derived TMNCs, C1GALT1 expression was similar in IgD+ naïve B cells, but was reduced in class-switched IgA+ B cells. In IgA+ TMNCs, IgA BCR stimulation reduced C1GALT1 expression, whereas ibrutinib increased it. Expression of GALNT14 was also regulated by BCR signaling.
Tonsillar IgA+ cells from IgAN patients exhibited opposing effects of BCR activation and Btk inhibition on expression of C1GALT1 and Gd-IgA1 production. A similar regulatory pattern was also observed for GALNT14. These findings suggest that both BCR and Btk affect glycosylation phenotypes of IgA-producing cells. Thus, Btk may represent a novel therapeutic target in IgAN.
