# Clinical utility of 1:16 serum dilution as a predictor of response to therapeutic plasma exchange for HLA antibody-mediated rejection treatment and overall survival in lung transplant recipients: A two center study

## TL;DR

This study shows that a 1:16 serum dilution test can predict how well lung transplant patients will respond to plasma exchange treatment for antibody rejection and their overall survival.

## Contribution

The study identifies 1:16 serum dilution HLA antibody testing as a novel predictor of TPE response and survival in lung transplant recipients with AMR.

## Key findings

- 1:16 serum dilution MFI strongly correlates with post-TPE MFI in both early and late AMR cases.
- Higher MFI in 1:16 diluted sera before TPE is linked to better survival outcomes in lung transplant recipients.
- Most AMR cases involved HLA Class II dnDSA, with fewer cases involving HLA Class I dnDSA.

## Abstract

Antibody-Mediated Rejection (AMR) due to HLA donor-specific antibodies (DSA) is associated with poor outcomes in lung transplant recipients (LTR). AMR treatment using therapeutic plasma exchange (TPE) improves clinical outcomes in LTR. The objective of this study was to assess the clinical utility of 1:16 serum dilution HLA antibody test results as a predictor of response to TPE for de novo DSA (dnDSA) levels and AMR treatment in LTR.

A retrospective analysis of 32 LTR diagnosed with AMR due to dnDSA and treated with TPE was performed at Mayo Clinic (n = 18) and Temple University Hospital (n = 14). HLA antibodies were detected by Luminex single antigen beads assay. Mean Fluorescence Intensity (MFI) levels were measured in undiluted and 1:16 diluted sera before the 1st and after the 5th TPE session. Statistical analysis was performed using GraphPad PRISM software.

Of 32 patients, 14 and 18 patients were diagnosed with early (< 3 months post-transplant) and late (6 months – 3 years post-transplant) AMR respectively. All patients, except one, had HLA Class II dnDSA (97%). In addition, 9/14 (64.2%) and 3/18 (16.6%) of LTR with early and late AMR respectively had HLA class I dnDSA. The MFI for all positive dnDSA in 1:16 diluted sera collected before 1st TPE demonstrated a significant correlation with MFI in undiluted sera collected after 5th TPE in both early (R2 = 0.8786) and late (R2 = 0.9045) AMR post-transplant. In addition, MFI in 1:16 diluted pre TPE sera correlated with better overall LTR survival following TPE (p = 0.001).

The MFI of 1:16 serum dilution before 1st TPE may be utilized as a surrogate to predict response to TPE for AMR treatment and overall survival in LTR.