OR48 Antibodies against vascular endothelial keratin 1 antigen associate with deterioration of renal allograft function

Abstract

Aim Non-HLA antigens have been found to involve in organ transplant rejection. Studies have shown that most of non-HLA antigens are targets of anti-endothelial cell antibodies (AECAs) and paly role on the antibody-mediated rejection (AMR), but these antigens on the surface of endothelial cells (EC) are not yet fully identified. Methods In this study, we isolated the anti-EC specific antibodies (IgG) for the serum AECAs of renal allograft recipients with antibody adsorption and elution by human endothelial cells. The response antigen(s) were captured via immunoprecipitation using AECA obtained. Results Mass spectrometry analysis showed that the endothelia antigen Keratin-1 (KRT1) was frequently found as the target transplant antigen. Three most common KRT1 alleles were cloned, expressed and purified, using KRT1 antigens as antigens we developed an ELISA to detect anti-KRT1 antibodies in the patients with renal transplantation. The results showed that the positive rate of serum KRT1 antibodies was 20.8% (53/255) in the renal transplant recipients. Further analysis of the specificity of the anti-KRT1 antibodies and recipient’s KRT1 genotype showed that 89.3% of the patients produced anti-KRT1 antibodies that reacted with their own KRT1 antigen, suggesting that the anti-KRT1 antibodies likely belong to autoantibodies. The recipients of renal transplantation were divided into two groups according to the serum creatinine (Cr) levels. Anti-KRT1 antibodies (IgG) were detected in 29.9% (23/77) recipients with Cr > 120 μmol/L, while, it was 16.9%(30/178) in kidney transplant recipients with Cr⩽120 μmol/L. The difference is statistically significant (x 2 = 5.531, P Conclusions Anti-KRT1 antibodies are associated with the deterioration of renal graft function after transplantation. Detection of anti-KRT1 IgG might be beneficial for the recipients after renal transplantation.