When Negative Isn’t Negative: Uncovering High-Risk Donor-Specific Antibodies Despite Negative PRA Results

Abstract

This letter highlights a critical diagnostic gap in pre-transplant immunological risk assessment: the presence of clinically significant anti-HLA antibodies in patients with negative Panel Reactive Antibody (PRA) screening results. Although a negative PRA is widely interpreted as absence of HLA sensitisation, our laboratory observations challenge this assumption. Among patients with PRA mean fluorescence intensity (MFI) values below 1000, Single Antigen Bead (SAB) assays identified strong anti-HLA antibodies with MFI levels ranging from 1207-5427. Notably, one case demonstrated high-titre Class I donor-specific antibodies (DSA) that were completely undetected by Class I PRA screening. These discrepancies likely reflect the pooled-antigen design of PRA assays, which may dilute or fail to represent specific epitopes detectable by SAB testing. Our findings suggest that reliance on PRA alone may underestimate immunological risk, supporting broader integration of SAB testing and high-resolution donor HLA typing to improve risk stratification and reduce the likelihood of antibody-mediated graft rejection.