Premium
Estimating alloantibody levels in highly sensitized renal allograft candidates: Using serial dilutions to demonstrate a treatment effect in clinical trials
Author(s) -
Tambur Anat R.,
Schinstock Carrie,
Maguire Chelsea,
Lowe David,
Smith Byron,
Stegall Mark
Publication year - 2021
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/ajt.16363
Subject(s) - medicine , titer , serial dilution , antibody , desensitization (medicine) , antibody titer , transplantation , concordance , immunology , gastroenterology , pathology , alternative medicine , receptor
Small reductions in calculated panel‐reactive antibody (cPRA) are associated with increased kidney transplantation in 100% cPRA patients. However, the high level of antibody in these patients is such that desensitization may reduce antibody but not cPRA, thus the cPRA change on undiluted serum with desensitization is an insensitive measure of effectiveness. We evaluated cPRA reduction, calculated per antibody titer, as a desensitization trial endpoint. To accomplish this, two serum samples from 20 kidney transplant candidates with cPRA ≥99.9% (100%) were obtained and serially diluted in triplicate to determine the titer of individual human leukocyte antigen (HLA) antibody specificities. CPRA was computed per dilution to identify the titer at which cPRA drops below 98%. Inter‐ and intra‐assay variability and changes overtime were determined. The dilution needed to reach a cPRA <98% was within 1 titer for replicates from the same sample, with 90% (36/40) concordance. This indicates that only changes >2 titers can be deemed clinically meaningful. The median (IQR) titer difference was 0 (0‐1) from baseline to follow‐up within 12 months. The cPRA per titer also risk‐stratified candidates for trial inclusion. In conclusion, determining the cPRA per titer is a reliable approach to simplify complex antibody data and an ideal endpoint for desensitization trials.