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 (DSA) against mismatched Human Leukocyte Antigens (HLA), which pose a significant challenge to successful transplantation of solid organs and hematopoietic cells. In this study, we evaluated the response to five TPE sessions in patients undergoing desensitization, as well as in patients who developed antibody-mediated rejection (AMR) post-transplant. 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 HLA antibodies correlated with previously established total IgG reduction levels. However, we observed that class I antibody levels were reduced by 85-90% while class II antibodies were reduced by only 75-80% after five TPE sessions. We also found that dilutions performed on pre-treatment 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 AMR. 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.