Título

AN APPROACH TO CHARACTERIZE AN ATYPICAL BW4 EPITOPE BASED ON THE NONSELF-SELF PARADIGM OF HLA IMMUNOGENICITY

Introdução

A 14 yrs old male patient with acute lymphoblastic leukemia relapse after a DSA negative-cord blood hematopoietic stem cell transplant (HSCT) was enrolled in the unrelated donor search.

Material e Método

Anti-HLA antibody (Ab) identification was performed using Single Antigen Beads (SAB) (LS1A04_Lot 09) and the result showed an unusual sub-Bw4 (80TLR) pattern with positive reactions for B13, B37, B44 and B47 (MFI: 5340 to 17191), but negative reaction with B*27:05 (MFI=16), that is also supposed to carry this Bw4 epitope. This epitope reactivity pattern (ERP) was confirmed by the phenotype panel (LS1PRA_Lot 16) and new lot of SAB (LS1A04_Lot 10). Epitope analysis using HLA Fusion and HLAMatchmaker (HMM) software couldn’t explain this unexpected ERP. Interestingly, B*37:01 was an HLA mismatch (immunizer) in the first HSCT, what brought out the possibility of de novo Ab.

Resultados

In order to clarify this finding, the HLA-Epitopia Map tool was utilized under the light of the nonself–self paradigm of HLA immunogenicity (NS-SPHI). Cn3d software was used to identify the structural epitope and its polymorphic surface residues. The assessment of the 80TLR+69TNT configuration, within the 15-Å radius, by HLA-Epitopia Map justified the unusual 80TLR pattern since negative B*27:05 had another configuration (80TLR+69AKA). After NS-SPHI evaluation, we verified that position 77 was the only difference among 19 residue positions between the immunizer’s B*37:01 and self-B*39:01 structural epitopes (77D versus 77S, respectively). These finding is consistent with NS-SPHI’s hypothesis.

Discussão e Conclusões

This report shows that HLA-Epitopia Map/NS-SPHI evaluations are valuable tools to analyze complex HLA-Ab ERP that cannot be explained by the standard HMM.

Palavras Chave

HLA Epitope, HLAMatchmaker, HLA-Epitopia Map, Nonself–Self Paradigm