# Interpreting immune evasion: a novel assay for HLA loss detection

## TL;DR

A new NGS assay is developed to detect HLA loss with high sensitivity, aiding in post-transplant monitoring and relapse management.

## Contribution

The novel NGS assay offers increased sensitivity and broader applicability for HLA loss detection without requiring prior HLA mismatch knowledge.

## Key findings

- The assay correlates well with the One Lambda Devyser Chimerism assay and has a detection limit of 0.25%.
- The assay's markers effectively identify HLA loss occurrence and location in post-transplant patients.
- Findings suggest the assay can influence clinical decisions regarding donor selection for retransplants or DLI.

## Abstract

This study presents the analytical performance of a new Next-Generation Sequencing (NGS) assay designed to detect Human Leukocyte Antigen (HLA) loss. Unlike existing methods, this assay offers increased sensitivity, broader applicability, and does not require prior knowledge of specific HLA mismatches, making it a more versatile tool for post-transplant monitoring. The main goal was to determine whether this assay can reliably identify HLA loss in post-transplant patients and provide clinically actionable information for relapse management. Furthermore, the clinical utility of the assay was assessed in patients undergoing Hematopoietic Stem Cell Transplantation (HSCT) with haploidentical or HLA-mismatched unrelated donors (MMUD). The study included both artificial and clinical samples, which were analyzed using the present assay to examine insertion-deletion (indel) markers located within and adjacent to the HLA region. The results demonstrated that the new assay exhibits excellent correlation with the One Lambda Devyser Chimerism assay in samples without HLA loss, achieving a detection limit of 0.25%. Furthermore, the study showed that the markers employed in the assay can effectively identify the occurrence and location of HLA loss. These findings could potentially influence clinical decision-making, when the donor source of retransplants or Donor Lymphocyte Infusions (DLI) need to be re-considered.