Measuring human leukocyte antigen alloantibodies: beyond a binary decision

Abstract

Accurate measurement of human leukocyte antigen antibodies is critical for making clinical decisions treating patients awaiting transplantation or monitoring them post transplantation. Single antigen bead assay results are given as Mean Fluorescence Intensity, falling short of providing the required quantitative measure. Titration studies were shown to circumvent the limitation of target-saturation that affect interpretation of single antigen bead assays especially in highly sensitized patients with strong antibodies. In fact, titration information can serve to measure efficacy of antibody removal during pretransplant desensitization using plasmapheresis/intravenous immunoglobulin (PP/IVIg) approaches. Moreover, recent studies indicate that knowing the donor-specific antibody titer has prognostic value that can guide PP/IVIg desensitization treatments. Newer data demonstrates an additional layer of information obtained by titration studies allowing to stratify patients with very high cPRA (>99%) based on the strength of the antibodies present, rather than the breadth. This data can thereby identify patients that are more likely to benefit from desensitization approaches on the transplant wait-list. Titration studies have a prognostic value with regards to quantifying antibody strength. Obtaining this information does not require performing the complete set of dilutions. In fact, performing two to three specific dilutions can provide relevant information while maintaining practical cost.