Guiding therapeutic plasma exchange for antibody‐mediated rejection treatment in lung transplant recipients – a retrospective study

Abstract

Summary Antibody‐Mediated Rejection (AMR) due to donor‐specific antibodies (DSA) is associated with poor outcomes after lung transplantation. Currently, there are no guidelines regarding the selection of treatment protocols. We studied how DSA characteristics including titers, C1q, and mean fluorescence intensity (MFI) values in undiluted and diluted sera may predict a response to therapeutic plasma exchange (TPE) and inform patient prognosis after treatment. Among 357 patients consecutively transplanted without detectable pre‐existing DSAs between 01/01/16 and 12/31/18, 10 patients were treated with a standardized protocol of five TPE sessions with IVIG. Based on DSA characteristics after treatment, all patients were divided into three groups as responders, partial responders, and nonresponders. Kaplan–Meier Survival analyses showed a statistically significant difference in patient survival between those groups (P = 0.0104). Statistical analyses showed that MFI in pre‐TPE 1:16 diluted sera was predictive of a response to standardized protocol (R2 = 0.9182) and patient survival (P = 0.0098). Patients predicted to be nonresponders who underwent treatment with a more aggressive protocol of eight TPE sessions with IVIG and bortezomib showed improvements in treatment response (P = 0.0074) and patient survival (P = 0.0253). Dilutions may guide clinicians as to which patients would be expected to respond to a standards protocol or require more aggressive treatment.

Mismatch epitope load predicts de novo‐DSA‐free survival in pediatric liver transplantation

“…A positive cutoff of 1000 MFI was used to identify positive DSA specificities. Antibody titers were determined by performing serial fourfold dilutions using PBS and EDTA‐treated sera (undiluted, 1:4, 1:16, 1:64, etc.,) as previously described 27 …”

“…Antibody titers were determined by performing serial fourfold dilutions using PBS and EDTA-treated sera (undiluted, 1:4, 1:16, 1:64, etc.,) as previously described. 27…”

Sensitization in transplantation: Assessment of Risk 2022 Working Group Meeting Report

“…Following this report, many laboratories have adopted testing of at least one serum dilution when antibodies of interest have mean fluorescence intensity (MFI) values >12 000 to 15 000 MFI units. More recently, Timofeeva et al 68,69 reported a successful implementation of this approach in exploring transplantation of highly sensitized heart transplant candidates and guiding ABMR therapy in lung transplant recipients.…”

DSA in solid organ transplantation: is it a matter of specificity, amount, or functional characteristics?

“…Studies in heart and lung transplantation evaluating the value of measuring HLA-DSAs (and C1q-binding status) before and after treatment of ABMR are sparse, uncontrolled and of small sample size. These have shown on selected patients with ABMR that HLA-DSA MFI, titer and C1q-binding capacity were significantly decreased after plasmapheresis, intraveinous immunoglobulin þ/proteasome inhibitors (including Bortezomib) [51][52][53].…”