Antibodies reactive with agrin in transplant glomerulopathy

Abstract

O427* Aims: About 15% of the patients with chronic renal allograft rejection show characteristics of chronic transplant glomerulopathy (TGP), including duplications of the glomerular basement membrane (GBM). We hypothesized that humoral immune responses are involved in TGP. Methods : We selected 18 cases with TGP showing double contours of the GBM on light microscopy. Patients with chronic rejection were used as controls. Paraffin sections were stained with polyclonal C4d antibodies. Sera of 13/18 patients were tested for anti-HLA and antibodies reactive with GBM. Results: Glomerular C4d deposits were present in a capillary pattern in 10/11 biopsies with TGP and in only 2/13 controls. Donor-specific anti-HLA antibodies were demonstrated in 6/13 patients and in 2/9 controls. Antibodies reactive with GBM isolates were detected in 9/13 patients and in 2/10 controls, but not directed to the Goodpasture antigen. Immuno-affinity purification yielded a large antigen. All patients with GBM reactivity had antibodies to this antigen. An antibody directed to the heparin sulphate proteoglycan (HSPG) agrin recognized the purified antigen. Indirect immunofluorescence with patient IgG showed a GBM-like staining pattern and co-localization with agrin. Conclusions: In TGP patients, glomerular C4d deposits were found, together with serum antibodies reactive with GBM isolates, suggesting a humoral tissue-specific immune response. Purified antigen was recognized by anti-agrin. A similar linear GBM staining pattern of patient sera and anti-agrin supported the potential role of the HSPG agrin in TGP.