Pre-transplant serum concentrations of anti-endothelial cell antibody in panel reactive antibody negative renal recipients and its impact on acute rejection

Abstract

Background: Endothelial cell antigens are important targets in acute rejection (AR). Our goal was to measure the serum concentrations of pre-transplant antiendothelial cell antibody (AECA) in panel reactive antibody (PRA) negative recipients and its impact on AR within 6 months following renal transplantation. Methods: We retrospectively examined pre-transplant sera from 392 patients using cellular enzyme linked immunosorbent assay (ELISA) with substrate from a permanent endothelial cell line EAhy926. Equal volumes of serum from 40 healthy volunteers were mixed and used as the negative control. Results: The positive rate of AECA was 15.8%. There were no significant differences with respect to age, gender, original disease, dialysis history, immune suppressive regimen, cytomegalovirus (CMV) antigen positive rate, complement dependent cytotoxicity (CDC) level and soluble CD30 (sCD30) levels between the AECA positive group and AECA negative group. AR rate in the AECA positive group was higher than that in the AECA negative group (35.5% vs. 22.4%, ps0.023). The AECA positive patients had significantly higher rates of acute grade II T-cell mediated rejection (TMR) and acute antibody mediated rejection (AMR) compared with AECA negative patients. The concentrations of sCD30, and AECA were independent risk factors for AR within 6 months; the odds ratios were 7.005 and 2.469, respectively. Conclusions: Positive AECA was an independent risk factor for AR and appeared to correlate with relatively severe rejection subtypes. Clin Chem Lab Med 2009;47:1265-9.

De novo development of circulating anti-endothelial cell antibodies rather than pre-existing antibodies is associated with post-transplant allograft rejection

“…The results of this study suggest that when compared with pre-existing AECAs, the presence of de novo AECAs might have a much stronger correlation with the development of post-transplant rejection. Earlier studies provided conflicting information with regard to the value of pre-existing AECAs in predicting rejection, 15,[23][24][25][26] and no such correlation was found in this study. The incidence of multiple acute rejections in this cohort was even lower than that in the AECA (À) group.…”

Pre-Transplant Angiotensin II Type 1 Receptor Antibodies and Anti-Endothelial Cell Antibodies Predict Graft Function and Allograft Rejection in a Low-Risk Kidney Transplantation Setting

“…Previous studies have provided evidence for the association between non-HLA antibodies, such as angiotensin II type 1 receptor antibodies (anti-AT1Rs) and anti-endothelial cell antibodies (AECAs), and acute rejection (AR) and/or graft failure [ 3 – 13 ]. Indeed, the allograft endothelium is the first barrier between self and non-self in vascularized solid organ transplantations and an active target of the host immune response [ 14 ].…”

Antigen and Cell-Based Assays for the Detection of Non-HLA Antibodies

“…It has been proposed that anti-AT 1 R and anti-HLA antibodies have a synergistic role in mediating kidney allograft rejection through the induction of overexpression of HLA molecules after binding to the ECs (19). AECAs can be detected with flow cytometry, ELISA, indirect immunofluorescence, and high-density protein array as described in this review, and most assays use either EPCs isolated from peripheral blood or HUVECs as an antigen substrate (25,37,75,76). A commercial kit for EC crossmatching is available, and it uses magnetic coated beads against angiopoietin receptor Tie-2 to isolate EPCs (XM-ONE).…”