Predicting the success of antibody removal with therapeutic plasma exchange: The role of serum dilutions

Therapeutic plasma exchange (TPE) remains a primary therapy for addressing circulating donor-specific antibodies against mismatched human leukocyte antigens, which pose a significant challenge to successful transplantation of solid organs and hematopoietic cells. In this study, we aimed to evaluate the response to 5 TPE sessions in patients undergoing desensitization, as well as in patients who developed antibody-mediated rejection posttransplant. Sera collected before and after each TPE session was treated with EDTA and tested using the single-antigen bead assay as undiluted or 1:4, 1:16, 1:64, and 1:256 diluted. The reduction in human leukocyte antigen antibodies correlated with previously established total immunoglobulin G reduction levels. However, we observed that class I antibody levels were reduced by 85% to 90% while class II antibodies were reduced by only 75% to 80% after 5 TPE sessions. We also found that dilutions performed on pretreatment serum were predictive of the response to TPE. This approach was used to design TPE-based desensitization protocols for highly sensitized patients across various organ and tissue types, as well as for treating patients with antibody-mediated rejection. Our data suggest that serum dilution may be an effective method for assessing the likelihood of response to TPE, thereby aiding in the guidance of treatment strategies.