Mitigating the Prozone‐Like Effect in HLA Antibody Testing: A Case Report of Therapeutic Plasma Exchange for Antibody‐Mediated Rejection Post‐Heart Transplantation

ABSTRACT Therapeutic plasma exchange (TPE) is a cornerstone treatment for antibody‐mediated rejection (AMR) post‐organ transplantation, aiming to eliminate pathogenic donor‐specific HLA antibodies (DSA). However, limitations in HLA antibody interpretation due to the prozone‐like effect (PLE) can lead to inaccurate assessment of treatment efficacy. We present a case of a heart transplant recipient with suspected AMR, where an unexpected increase in DSA levels post‐TPE prompted investigation into PLE. Solid‐phase Luminex assays were employed to detect HLA antibodies. Serum was run neat as well as after treatment with ethylenediaminetetraacetic acid (EDTA). Nephelometry was used to detect complement levels. Laboratory analysis of pre‐TPE serum revealed higher DSA levels with EDTA treatment, characteristic of PLE. Complement measurements supported complement‐mediated interference in the pre‐TPE sample. This case underscores the importance of being aware that PLE can occur in HLA testing and can impact the interpretation of TPE efficacy for AMR.