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Highlights: [•] Pepsin hydrolysates of legume proteins have ACE-inhibitory activity. [•] Lupin and soybean proteins show the lowest IC50 values. [•] Two globulins, α and β conglutin, are responsible for lupin ACE-inhibitory activity. [ABSTRACT FROM AUTHOR]

Summary: Pocket motifs and their amino acid positions of HLA molecules are known to govern antigen presentation to effector cells. Our objective was to analyse their influence on the risk of graft‐versus‐host disease (GVHD) and relapse after umbilical cord blood transplant (UCBT). The transplant characteristics of 849 patients with acute leukaemia were obtained from the Eurocord/EBMT database. Higher acute (a) GVHD was associated with homozygosity of UCB HLA‐C amino acid positions 77 and 80 (NN/KK) (p = 0.008). Severe aGVHD was associated with HLA‐A pocket B YSAVMENVHY motif (p = 0.002) and NN and RR genotypes of the HLA‐C amino acid positions 77 and 156 (p = 0.006 and p = 0.002). Such risk was also increased in case of recipient and UCB mismatches in P4 (p < 0.0001) and P9 (p = 0.003) pockets of HLA‐DQB1 alleles. For chronic GVHD, the pocket B YYAVMEISNY motif of the HLA‐B*15:01 allele and the absence of mismatch between recipient and UCB in the P6 pocket of HLA‐DRB1 were associated with a lower risk (p = 0.0007 and p = 0.0004). In relapse, both UCB pocket B YFAVMENVHY belonging to HLA‐A*32:01 and recipient pocket B YDSVGENYQY motif of the HLA‐C*07:01 allele were associated with higher risk (p = 0.0026 and p = 0.015). We provide clues on HLA‐mediated cellular interactions and their role in the development of GVHD and relapse. [ABSTRACT FROM AUTHOR]

Summary: The association between acute lymphoblastic leukaemia (ALL) and acute myeloid leukaemia (AML) and the human leukocyte antigens (HLA) has rarely been studied in terms of diversity of peptide‐binding pockets. The objective of this study was to analyse whether motifs of HLA class I and class II peptide‐binding pockets and/or their amino acid positions were differentially associated with ALL and AML. We included 849 patients from the Eurocord/European Blood and Marrow Transplant registry. The HLA peptide‐binding pockets whose amino acid variability was analysed were B and F for HLA class I, P4, P6, and P9 for HLA‐DRB1, and P4 and P9 for HLA‐DQB1. The motif RFDRAY in P4 of HLA‐DRB1*16:01/02/03/05 alleles and the motif YYVSY in P9 of HLA‐DQB1*05:02/04/05 alleles, were statistically associated with ALL (corrected p value [pc] = 0.001 and pc = 0.035 respectively). The frequency of serine 57 in the P9 of HLA‐DQB1 was higher in ALL (odds ratio 2.09, 95% confidence interval: 1.27–3.44; pc = 0.037). Our analysis suggests that specific motifs in terms of HLA class II pockets and amino acids might be unique to ALL. The associations identified in this study encourage further investigation oF the role of HLA peptide‐binding pockets and their amino acids in immune processes underpinning acute leukaemia and ultimately in immunotherapy settings. [ABSTRACT FROM AUTHOR]

• Patients with sickle cell disease (SCD) belong to ethnic groups underrepresented in donor registries. • We assessed chances of finding a matched unrelated donor by geographical origin. • Brazilian patients showed a greater genetic admixture than European Society for Blood and Marrow Transplantation patients. • However, chances of having a potential allelic matched unrelated donor were equal in the 2 groups (47%). • Further strategies to improve donor representativity are warranted in the SCD setting. Sickle cell disease (SCD) is the most common inherited hemoglobinopathy. Hematopoietic stem cell transplantation (HCT) is the sole curative therapy for SCD, but few patients will have a matched sibling donor. Patients with SCD are mostly of African origin and thus are less likely to find a matched unrelated donor in international registries. Using HaploStats, we estimated HLA haplotypes for 185 patients with SCD (116 from a Brazilian center and 69 from European Society for Blood and Marrow Transplantation [EBMT] centers) and classified the ethnic origin of haplotypes. Then we assessed the probability of finding an HLA-matched unrelated adult donor (MUD), considering loci A, B, and DRB1 (6/6), in international registries. Most haplotypes were African, but Brazilians showed a greater ethnic admixture than EBMT patients. Nevertheless, the chance of finding at least one 6/6 potential allelic donor was 47% for both groups. Most potential allelic donors were from the US National Marrow Donor Program registry and from the Brazilian REDOME donor registry. Although the probability of finding a donor is higher than previously reported, strategies are needed to improve ethnic diversity in registries. Moreover, predicting the likelihood of having an MUD might influence SCD management. [ABSTRACT FROM AUTHOR]