TORNA ALL’ELENCO

HSC transplant: Role of amino acid substitutions in antigen binding sites in HLA

2022
AOU Città della Salute di Torino

Tipo pubblicazione

Conference Abstract

Autori/Collaboratori (16)Vedi tutti...

Bertinetto FE
AOU Città della Salute e della Scienza di Torino, Italy
Bongioanni D
AOU Città della Salute e della Scienza di Torino, Italy
Amoroso A
AOU Città della Salute e della Scienza di Torino, Italy

et alii...

Abstract

Robust evidence supports the adverse impact of donorrecipient HLA disparity on Hematopoietic Stem Cell Transplantation (HCT) outcomes and thus it is necessary to investigate the relationship between mismatches and transplant outcome as a 10/10 match cannot be found for all patients in need of transplantation. Interesting studies conducted on amino acid substitutions (AAS) in the antigen binding sites showed the relevance of HLA-B mismatches in position 9 (chronic GvHD increase), HLA-C in position 99 (increase in transplant-related mortality) and HLA-C in position 116 (acute GvHD increase). These mismatches are classified as nonpermissive if they lead to an amino acid change. We studied the impact of these AAS on the transplant outcome of donor-recipient pairs from 2005 to now in collaboration with the Transplant Center (Molinette of Turin). Patients and donors had completed high-resolution typing for HLA-A, -B, -C, -DRB1 and -DQB1 (GenDx kits). In this period 931 patients underwent an HSC allograft. The study included 430 patients who received a first transplant from haploidentical sibling donors (HAPLO 106), MUD 10/10 (239), MUD 9/10 with a permissive mismatch at HLA-B or HLA-C (P-MM 46), MUD 9/10 with a non-permissive mismatch at the same loci (NP-MM 39). We analyzed patient survival related to different variables like gender, age, original disease of recipient, onset and severity of GvHD, source of HSC. The survival at 3 years in recipients of HAPLO, MUD and P-MM transplants is similar (53%), while it is less for NP-MM (34%). The survival at 5 years for P-MM is 52% significantly better than for NPMM transplants (32%, p = 0.04). This relevant information will be provided to the transplant center as a tool for the selection of donors.

DOI : 10.1111/tan.14606

Keywords

female; conference abstract; controlled study; antibody combining site; amino acid substitution; endogenous compound; HLA A antigen; HLA B antigen; HLA C antigen; HLA DQB1 antigen; adult; allograft; human; human tissue; major clinical study; male; matched unrelated donor; outcome assessment; overall survival; sibling donor; surgery; gender; graft versus host reaction;