Prevalence of Circulating Donor Specific Anti-HLA Antibodies and C4d Deposition in Live Renal Transplant Recipients with Chronic Allograft Dysfunction

Abstract

Introduction and aims: The detection of donor specific antibodies (DSA) and C4d staining of renal allograft biopsies has emerged as an important tool for the diagnosis of alloantibody dependent allograft injury. The present study was undertaken to determine the prevalence of circulating donor reactive anti-HLA class I and II antibodies and peritubular capillary C4d deposition in biopsies of patients with chronic allograft dysfunction. Methods: Thirty six live donor renal allograft recipients with graft dysfunction at more than one year post transplant based on serum creatinine of more than 2 mg% or proteinuria more than 600 mg were evaluated by graft biopsy and ELISA for presence of circulating IgG DSA. Biopsies were assessed by 3 independent pathologists based on light microscopy, immunofluorescence and C4d staining. Results: Of the 36 biopsies 10 had evidence of antibody mediated rejection (AMR), 11 showed evidence of transplant glomerulopathy (TG) and 12 were C4d positive (11 diffuse and 1 focal). All C4d positive biopsies had evidence of AMR (n=4), TG (n=3) or both (n=5). Of the 10 biopsies with AMR, 9 were C4d positive while 8 out of 11 biopsies showing TG also showed C4d positivity. Three patients had circulating donor specific anti-HLA class II antibodies alone. Of these one patient had membranous glomerulonephritis progressing to graft loss, another had acute cellular rejection (ACR) and the last had arterionephrosclerosis. Conclusions: There was good correlation between C4d and antibody mediated changes (AMR or TG). The presence of C4d positivity was significantly associated with graft loss or persistent graft dysfunction (P< 0.001). There was no correlation between DSA and AMR, TG or C4d staining.