Assessment by Extended-Coverage Next-Generation Sequencing Typing of DPA1 and DPB1 Mismatches in Siblings Matching at HLA-A, -B, -C, -DRB1, and -DQ Loci

Abstract

Allogeneic hematopoietic stem cell transplant from an HLA matched sibling donor is usually the preferable choice. The use of next-generation sequencing (NGS) for HLA typing in clinical practice provides broader coverage and higher resolution of HLA genes. We evaluated the frequency of DPB1 crossing-over events among patients and potential related donors typed with NGS. From July 2016 to January 2018, 593 patients and 2385 siblings were typed. We evaluated sibling matching status in 546 patients, and 44.8% of these patients had siblings that matched at HLA-A,-B,-C,-DRB1, and-DQB1 loci. In 306 patientÀHLA matched sibling pairs, we found 6 pairs (1.96%) with 1 DPB1 mismatch, and 5 of these pairs included an additional mismatch in DPA1. No additional mismatches were observed at the low expression loci. Using the T cell epitope algorithm, 4 of these DP mismatches were classified as permissive, 1 as nonpermissive in the host-versus-graft direction, and 1 as nonpermissive in the graft-versushost direction. The frequency of DPB1 and DPA1 mismatches is low, and their impact in related donor transplants is not well established. Although DP typing in related transplants goes beyond guidelines, it is especially relevant for sensitized patients. NGS-based HLA typing provides full gene coverage, and its use in clinical practice can enable better donor selection.

Joint models quantify associations between immune cell kinetics and allo-immunological events after allogeneic stem cell transplantation and subsequent donor lymphocyte infusion

“…The alloreactive T-cell expansion may have been more easily detectable in patients with an UD compared to RD because of the deeper lymphopenia at time of DLI due to the long-lasting immunosuppressive effect of ATG that patients with an UD received ( 13 ). In addition, the high prevalence of HLA-DP mismatches, targeted by CD4+ T-cells, in patients with an UD ( 32 – 34 ) could contribute to the strong association between CD4+ T-cells and the development of GvHD. In contrast to T-cells, NK cells recovered early after alloSCT and were not significantly influenced by donor type and TCD, consistent with previous studies ( 13 , 35 , 36 ), nor by DLI.…”