Showing papers by "Eliane Gluckman published in 2022"

Comparative analysis of the variability of the human leukocyte antigen peptide‐binding pockets in patients with acute leukaemia

Abstract: 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.

P1469: longitudinal sickle cell disease cohort-study: in children with splenic sequestration history or hypersplenism, partial vs total splenectomy before stem cell transplantation preserves spleen function

Abstract: Background: Background: The presence of Howell-Jolly bodies (HJB) is associated with splenic dysfunction that appears progressively during aging or after splenectomy in patients with sickle cell disease (SCD). Improvement of splenic function has been found in several SCD patients after transplantation, prompting our team to propose a partial splenectomy prior to transplantation to patients with hypersplenism and available matched-sibling donor (MSD) Aims: Aims: To evaluate splenic function from birth to adulthood, the impact of intensive treatments: hydroxyurea (HU), chronic transfusion (CT), transplantation and compare the impact of splenectomy (partial/total) in SCD patients when transplanted or not Methods: Methods: Scores for HJB (0 to 3) were assessed on blood smears in the pediatric Créteil SCD-cohort and prospectively recorded at each annual check-up. This study included 4103 annual check-ups with available HJB score and all other biological parameters: Hb, HbA%, HbS%, HbF%, platelets etc.. performed in 907 SCD patients (111 SC, 47 Sb+, i.e Summary/Conclusion: Summary/Conclusion: The higher number of RBCs containing HJBs observed on HU is intriguing and could be related to altered erythropoisesis kinetics, drug-induced genotoxicity or altered splenic function because of drug-induced high MCV. This cohort study clearly shows that splenic dysfunction increases with aging in SCA children and that stem cell transplantation allows to preserve splenic function, especially if the transplant is performed early. In children with indication of splenectomy for recurrent splenic sequestrations or hypersplenism who have an available MSD, the present study suggests that partial splenectomy just before stem cell transplantation may be useful to preserve splenic function.

Umbilical Cord Blood Stem Cells (UCBSC) [1]

Abstract: Umbilical cord blood (UCB) stem cells [4] are hematopoietic stem cells [5] (HSC) that are recovered from the blood of the umbilical cord [6] and placenta [7] after birth. Umbilical cord blood is rich in cells that express the CD34 molecule, a surface protein that identifies cells as stem cells [4] . Prior to the discovery of UCB stem cells [4] , it was standard procedure to discard the umbilical cord [6] and placenta [7] ; now much effort is devoted to raising public awareness and to encouraging people to store or donate cord blood. The importance of these cells lies in potential clinical treatments of blood-borne diseases, as well as the possibility of restoring cells of other lineages, such as cardiac and neural cells. These possible uses have given rise to cord blood stem cell banking [8] , both private and public, where cells can be frozen and stored for later use. their Umbilical Cord Blood as a Potential Source of Transplantable Hematopoietic Stem/Progenitor Cells,” . cord and placenta; now much effort is devoted to raising public awareness and to encouraging people to store or donate cord blood. The importance of these cells lies in potential clinical treatments of blood-borne diseases, as well as the possibility of restoring cells of other lineages, such as cardiac and neural cells. These possible uses have given rise to cord blood stem cell banking, both private and public, where cells can be frozen and stored for later use.

Pb1752: analysis of hla-peptide binding pockets in patients with acute leukemia undergoing umbilical cord blood transplantation

Abstract: Background: Background: Despite a better understanding of the genetic heterogeneity of both acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML), relapse rates remain high and long-term survival is suboptimal. In this context, the association between these malignancies and the human leukocyte antigens (HLA) has been widely studied. The highly polymorphic HLA loci have significance and relevance for disease susceptibility thanks to their peptide-binding grooves-dependent antigen presentation to effector cells. Such processes trigger an algorithm of immune responses based on multiple fine-tuned combinations of amino acid sequence interactions. Thus, the HLA genetic diversity has been a focus of interest in acute leukemia settings as exemplified by studies showing the implication of both HLA class I and II polymorphisms. However, there is scarce data regarding the diversity of peptide-binding pockets per se especially in the context of umbilical cord blood transplantation (UCBT). Aims: Aims: To analyze whether variants of HLA-DQB1 and -DRB1 peptide-binding groove pockets 4 and 9 and/or their amino acid positions are associated with the diagnosis of ALL or AML among patients undergoing UCBT. Methods: Methods: A retrospective analysis was performed including 849 patients with ALL and AML undergoing an UCBT. Demographics and genotyping

Possible Effect of the use of Mesenchymal Stromal Cells in the Treatment of Autism Spectrum Disorders: A Review

Abstract: Autism spectrum disorder (ASD) represents a set of heterogeneous neurodevelopmental conditions defined by impaired social interactions and repetitive behaviors. The number of reported cases has increased over the past decades, and ASD is now a major public health burden. So far, only treatments to alleviate symptoms are available, with still unmet need for an effective disease treatment to reduce ASD core symptoms. Genetic predisposition alone can only explain a small fraction of the ASD cases. It has been reported that environmental factors interacting with specific inter-individual genetic background may induce immune dysfunctions and contribute to the incidence of ASD. Such dysfunctions can be observed at the central level, with increased microglial cells and activation in ASD brains or in the peripheral blood, as reflected by high circulating levels of pro-inflammatory cytokines, abnormal activation of T-cell subsets, presence of auto-antibodies and of dysregulated microbiota profiles. Altogether, the dysfunction of immune processes may result from immunogenetically-determined inefficient immune responses against a given challenge followed by chronic inflammation and autoimmunity. In this context, immunomodulatory therapies might offer a valid therapeutic option. Mesenchymal stromal cells (MSC) immunoregulatory and immunosuppressive properties constitute a strong rationale for their use to improve ASD clinical symptoms. In vitro studies and pre-clinical models have shown that MSC can induce synapse formation and enhance synaptic function with consequent improvement of ASD-like symptoms in mice. In addition, two preliminary human trials based on the infusion of cord blood-derived MSC showed the safety and tolerability of the procedure in children with ASD and reported promising clinical improvement of core symptoms. We review herein the immune dysfunctions associated with ASD provided, the rationale for using MSC to treat patients with ASD and summarize the current available studies addressing this subject.