P246 Epitope analysis for stem cell transplant. A case study

Abstract

Aim The role of HLA antibodies (Ab) in allogeneic hematopoietic stem cell transplant (HSCT) is being recognized due to the significant increase in unrelated HSCT with some degree of mismatch as well as haploidentical transplants (Tx). HLA Ab may lead to graft failure, graft versus host disease and other post-Tx complications in HSCT. Hence, defining donor specific antibody (DSA) may be relevant for these transplant modalities. Epitope analysis is becoming an accepted tool helping elucidating the complexities of HLA Ab reactivity. Here we present a HSCT case where epitope analysis helped to predict reactivity of the patient Ab to the donor antigens and therefore, assess the suitability of the donor for this Tx. Methods HLA typing for the patient and donor were done with NGS (MiSeq and Holotype kit by Omixon) and analyzed with Target (Omixon) and NGSEngine (GenDx) software. Ab screening was performed using Single Antigen Beads (SAB) test (One Lambda). The cut off for positivity stablished in our lab for SAB is > 1500. Epitope analysis was done with HLAMatchmaker algorithm. Results A 5 year-old HSCT candidate had 2 HLA Ab specificities detected in her serum. They were A∗11:02 (MFI 1780) and DR16 (MFI 2567). None of them were DSA against her potential donor. Although the A2 specificities present in the SAB (A∗02:01, A∗02:03 & A∗02:06) test were negative, A∗02:11 included in the donor’s typing, is not represented in the panel. To assess potential reactivity against A∗02:11, epitope analysis was performed. Considering that A∗02:01, A∗02:03 & A∗02:06 were negative, any common epitope among them and A∗02:11 would suggest absence of reactivity to those epitopes. The only epitope that differs between A∗02:11 and the other A2 specificities present in the panel was the 69AI eplet. However, this eplet (69AI) was present in the patient self-allele A∗33:03, therefore suggesting that no Ab against A∗02:11 should had been developed. Conclusion This HSCT case report demonstrates that the combination of high resolution typing and epitope analysis may help resolving patient anti-HLA reactivity against potential mismatches, for which no beads are available to assess reactivity with the patient serum.