1138 Poster Board I-160 Background The MHC class I-related chain A (MICA) molecules is of particular in non T-cell receptor (TCR)-mediated immune function. MICA engages NKG2D, a C-type lectin expressed on effector cells including NK, and T cells. Such engagement triggers NK cells and co-simulates T lymphocytes to mount adequate immune response. Further, a soluble isoform of MICA (sMICA) has been implicated in the pathogenesis of a variety of cancers, auto-immune and other organ transplant-related disorders through NKG2D receptor down regulation. Functionally relevant polymorphism of the MICA gene may also contribute to inter-patients variability in allo-immune responses as observed in various clinical settings including organ-transplantation. A methionine (met) to valine (val) change at position 129 of the alpha 2-heavy chain domain categorized the MICA alleles into strong (MICA-129 met) and weak (MICA-129 val) binders of NKG2D receptor. Given the demonstrated importance of MICA in immune pathways, in this study, we explored the MICA-related parameters namely MICA-129 gene polymorphism, pre- and post-transplant serum levels of soluble MICA (sMICA) and anti-MICA antibodies (MICA Abs) in a HLA-matched sibling HSCT setting. Results We evaluated whether MICA-129 gene polymorphism, pre- and post-HSCT sMICA and MICA Abs could influence the incidence of chronic graft-versus-host disease (c.GvHD) and relapse of their disease in 211 HLA-identical sibling pairs. In multivariate analysis on chronic GvHD risk, 3 factors reached significance: recipient MICA-129 val/val genotype (HR = 1.52; 95% confidence interval [95%CI] = 1.02-2.24; P =.04), older recipient age (3 15 years) (HR = 3.36; 95%CI = 1.65-6.84; P =.001) and source of stem cells (PBSC vs BM) (HR = 1.67; 95%CI = 1.10-2.53; P =.017). Since acute GvHD (aGvHD) is a major risk factor of subsequent c.GvHD, we then introduced aGvHD as a time-dependant co-variate in the multivariate analysis model. This analysis confirmed that the risk conferred by the MICA-129 val/val genotype is independent from aGvHD. Elevated post-HSCT sMICA serum levels were also independently associated with c.GvHD (p =.0001) regardless of history of acute GvHD. On the contrary, the presence of pre-transplant MICA Abs confers protection against c.GvHD (p =.04). There was an inverse relationship between MICA Abs and sMICA suggesting an antibody-based neutralization of deleterious effects of sMICA. Similarly, these genetic and phenotype characteristics of MICA influence the incidence of relapse. Conclusion Altogether, these data suggest that the studied MICA genotype and phenotype specificities could be used as relevant biomarkers for c.GvHD monitoring. Disclosures No relevant conflicts of interest to declare.

SummaryDNA samples from 465 blood donors living in 7 towns of Sicily, the largest island of Italy, have been collected according to well defined criteria, and their genetic heterogeneity tested on the basis of 9 autosomal microsatellite and mitochondrial DNA polymorphisms for a total of 85 microsatellite allele and 10 mtDNA haplogroup frequencies. A preliminary account of the results shows that: a) the samples are genetically heterogeneous; b) the first principal coordinates of the samples are correlated more with their longitude than with their latitude, and this result is even more remarkable when one outlier sample (Butera) is not considered; c) distances among samples calculated from allele and haplogroup frequencies and from the isonymy matrix are weakly correlated (r = 0.43, P = 0.06) but such correlation disappears (r = 0.16) if the mtDNA haplogroups alone are taken into account; d) mtDNA haplogroups and microsatellite distances suggest settlements of people occurred at different times: divergence times inferred from microsatellite data seem to describe a genetic composition of the town of Sciacca mainly derived from settlements after the Roman conquest of Sicily (First Punic war, 246 BC), while all other divergence times take root from the second to the first millennium BC, and therefore seem to backdate to the pre-Hellenistic period.A more reliable association of these diachronic genetic strata to different historical populations (e.g. Sicani, Elymi, Siculi ), if possible, must be postponed to the analysis of more samples and hopefully more informative uniparental DNA markers such as the recently available DHPLC-SNP polymorphisms of the Y chromosome.

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.