title: Antibody response against the glomerular basement membrane protein agrin in patients with transplant glomerulopathy.
abstract: Chronic allograft nephropathy (CAN) of renal allografts is still the most important cause of graft loss. A subset of these patients have transplant glomerulopathy (TGP), characterized by glomerular basement membrane (GBM) duplications, but of unknown etiology. Recently, a role for the immune system in the pathogenesis of TGP has been suggested. In 11 of 16 patients with TGP and in 3 of 16 controls with CAN in the absence of TGP we demonstrate circulating antibodies reactive with GBM isolates. The presence of anti-GBM antibodies was associated with the number of rejection episodes prior to diagnosis of TGP. Sera from the TGP patients also reacted with highly purified GBM heparan sulphate proteoglycans (HSPG). Indirect immunofluorescence with patient IgG showed a GBM-like staining pattern and colocalization with the HSPGs perlecan and especially agrin. Using patient IgG, we affinity purified the antigen and identified it as agrin. Reactivity with agrin was found in 7 of 16 (44%) of patients with TGP and in 7 of 11 (64%) patients with anti-GBM reactivity. In conclusion, we have identified a humoral response against the GBM-HSPG agrin in patients with TGP, which may play a role in the pathogenesis of TGP.
authors.affiliation: Department of Nephrology, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Simone A
authors.initials: SA
authors.lastname: Joosten
authors.forename: Yvo W J
authors.initials: YW
authors.lastname: Sijpkens
authors.forename: Vanessa
authors.initials: V
authors.lastname: van Ham
authors.forename: Leendert A
authors.initials: LA
authors.lastname: Trouw
authors.forename: Johan
authors.initials: J
authors.lastname: van der Vlag
authors.forename: Bert
authors.initials: B
authors.lastname: van den Heuvel
authors.forename: Cees
authors.initials: C
authors.lastname: van Kooten
authors.forename: Leendert C
authors.initials: LC
authors.lastname: Paul
mesh_terms: D018171:Agrin / Q000276:immunology*; D000906:Antibodies / Q000276:immunology; D001485:Basement Membrane / Q000276:immunology; D006084:Graft Rejection / Q000276:immunology*; D006801:Humans; D007678:Kidney Glomerulus / Q000276:immunology*; D016030:Kidney Transplantation
chemical_list: D018171:Agrin; D000906:Antibodies