Interpretation of Positive Flow Cytometric Crossmatch in the Era of the Single-Antigen Bead Assay

Abstract

Prognosis of renal transplants with positive flow cytometric crossmatch (FCXM) remains controversial. We analyzed the outcome of these kidney transplant recipients by human leukocyte antigen (HLA) donor-specific antibodies (HLA-DSA) using single-antigen bead (SAB) assays in major histocompatibility complex classes I and II. We compared them with controls with a negative FCXM. Forty-five patients consecutively transplanted with a positive FCXM had significantly more acute rejection episodes than the control patients (33.3% vs. 8.9%, P=0.002). Risk of acute rejection was increased with day 0 (D0) positive T-cell FCXM (odds ratio [OR]=9.04, P=0.002), D0 positive B-cell FCXM (OR=7.43, P=0.02), and D0 HLA-DSA identified by SAB assay (OR=6.5, P=0.03). The 21 patients with D0 positive FCXM and D0 HLA-DSA had more acute rejection (62%, P=0.0001) and a lower estimated glomerular filtration rate 1-year posttransplantation (P=0.0001), when compared with controls. Mainly anti-Cw and anti-DP HLA-DSA were found in patients displaying acute rejection. The remaining FCXM-positive patients displayed short-term outcomes similar to controls. The presence of HLA-DSA detected only by the SAB assay in the context of a negative FCXM crossmatch was not associated with increased risk of acute rejection. Identification of HLA-DSA in D0 sera by the two sensitive techniques FCXM and SAB assay indicates which patients are at highest risk of subsequent acute allograft rejection and chronic allograft dysfunction.