Pathogenic Pathways of the renal damage in Fabry nephropathy: interplay between immune cell infiltration, apoptosis and fibrosis

FERIOZZI S; BONDAR C; BOLLA M; NEUMANN P; ROZENFELD PA

Simposio; 8th Fabry update; 2024

Background: Fabry nephropathy(FN) is due to a consequence of the cellular deposition of globotriaosylceramide caused by deficient GLA enzyme activity. These deposits are sensed as damage signals leading to the activation of inflammation, resulting in renal fibrosis. There are scarce studies related to immunophenotype characterization of the renal infiltrate in FN and its relationship to mechanisms of fibrosis. Methods: Renal biopsies from treatment naïve Fabry patients underwent histological analysis. Immunostaining was performed for active caspase 3, TGF-β1, TNF-α, CD3, CD20, CD68 and CD163. The aim was to quantify TGF-β1 and active caspase-3 expression, analyze the cells' profile in inflammatory infiltration, and investigate correlations with clinical parameters. Results: We revealed that tubular cells' production of TNFα and TGFβ1 from FN active caspase 3 staining showed tubular cells are in apoptosis, and apoptotic levels correlated with clinical signs of chronic kidney disease. The cell infiltrates are macrophages, T and B cells. CD163 macrophages were found in FD, whose numbers correlate with TGFβ1 and active caspase 3 tubular expressions. Conclusions: These results suggest that CD163+ cells could be a new player as cellular mediators of fibrosis in FN through the induction of TGFβ1 and apoptotic cell death by tubular cells.