title: Mechanisms underlying sCD40 production in hemodialysis patients.
abstract: CD40 and its ligand (CD40L) regulate several cellular functions, including T and B-cell activation. The soluble form of CD40 (sCD40) antagonizes CD40/CD40L interaction. Patients undergoing hemodialysis (HD) present elevated sCD40 serum levels, which underlying molecular mechanisms are unknown. We studied sCD40 serum and urinary levels, CD40 membrane and gene expression and membrane shedding in HD, uremic not-HD patients (UR) and healthy subjects (N). We found that in HD sCD40 serum levels were higher than UR and N, being significantly elevated in anuric patients, and that sCD40 correlated to renal function in UR subjects, who presented also a reduced sCD40 urinary excretion rate. HD and UR presented reduced CD40 membrane and gene expression. The concentration of TNF-α converting enzyme (TACE), responsible for CD40 cleavage was not different between HD and N. Therefore the reduced renal clearance is the main cause of elevated sCD40 levels in HD. This finding could have relevant clinical implications.
authors.affiliation: Department of Nephrology, Dialysis and Transplantation, Fondazione IRCCS Policlinico San Matteo, and University of Pavia, Italy. pasqualeesposito@hotmail.com
authors.forename: Pasquale
authors.initials: P
authors.lastname: Esposito
authors.forename: Teresa
authors.initials: T
authors.lastname: Rampino
authors.forename: Marilena
authors.initials: M
authors.lastname: Gregorini
authors.forename: Elisa
authors.initials: E
authors.lastname: Gabanti
authors.forename: Stefania
authors.initials: S
authors.lastname: Bianzina
authors.forename: A
authors.initials: A
authors.lastname: Dal Canton
mesh_terms: D051722:ADAM Proteins / Q000097:blood* / Q000235:genetics / Q000276:immunology; D000072198:ADAM17 Protein; D000368:Aged; D000369:Aged, 80 and over; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D019013:CD40 Antigens / Q000096:biosynthesis / Q000097:blood* / Q000235:genetics / Q000652:urine*; D023201:CD40 Ligand / Q000097:blood / Q000276:immunology; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D007668:Kidney / Q000276:immunology / Q000473:pathology; D007677:Kidney Function Tests; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis; D012995:Solubility; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
chemical_list: D019013:CD40 Antigens; D023201:CD40 Ligand; D051722:ADAM Proteins; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human