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

BONDAR, C.; BOLLA M; NEUMANN P; PISANI A; FERIOZZI S; ROZENFELD PA

JN. JOURNAL OF NEPHROLOGY

WICHTIG EDITORE

Lugar: Milán (Italia); Año: 2024

1121-8428

Background:Fabry nephropathy in Fabry disease patients isaconsequence of the deposition of globotriaosylceramide,caused by deficient GLAenzymeactivity in all types of kidney cells. These depositsare perceived as damagesignals leadingto activation of inflammation resultingin renalfibrosis. Therearefewstudies related to immunophenotypecharacterization of therenal infiltratein Fabry kidneysand its relationship tomechanisms of fibrosis.Methods:Renal biopsies fromtreatment-naïve Fabry patients wereincluded in this study,and subjected to histologicalanalysis. Immunostainingwasperformed to analyzestainingforactivecaspase 3, TGF-β1, TNF-α, CD3, CD20, CD68 and CD163. This work aims to quantify TGF-β1 andactivecaspase-3 expression and to analyzethe profile ofcells in inflammatory infiltration in kidney biopsies fromFabry naïve-patients,and toinvestigatecorrelations with clinical parameters.Results:Werevealed the production of TNFα and TGFβ1 by tubularcells fromtherenal biopsies of Fabry patients. Activecaspase 3 stainingrevealedthat tubularcellsarein apoptosis,and apoptoticlevelscorrelatedwith clinicalsigns ofchronic kidney disease, proteinuria,and inversely withglomerular filtration rate. Thecell infiltratesconsisted ofmacrophages, T and Bcells. CD163macrophages werefound in Fabry specimenswhose numberscorrelatewith TGFβ1 and activecaspase 3 tubularexpressions.Conclusions:Theseresults suggest that CD163+ cellscould berelevant cellularmediators of fibrosis in Fabry nephropathy, playingarolein theinduction ofTGFβ1 and apoptoticcell death by tubularcells. Thesecells would represent another newplayer in the pathogenicmechanisms of Fabrynephropathy