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D'Alessandro A.,University of Tuscia | D'Alessandro A.,Italian National Blood Center | Liumbruno G.,Italian National Blood Center | Liumbruno G.,Immunohematology and Transfusion Medicine Unit | And 4 more authors.
Journal of Proteomics | Year: 2010

The first umbilical cord blood (UCB) transplant to a sibling with Fanconi's anaemia in 1988 represented a breakthrough in the field of transplantation. Thereon, several transplants have been performed with UCB-derived hematopoietic stem cells (HSCs) and a plethora of studies have investigated the plasticity of UCB-derived stem and progenitor cells. However, these studies have not been hitherto translated into clinical trials and, although UCB is routinely used as an alternative source of HSCs, no substantial advances have been made in the field of clinical regenerative medicine. The real deal is the lack of knowledge about the molecular processes governing the events of differentiation which transform immature UCB stem cells into terminally-committed hematopoietic, muscle, bone and nervous cells. In order to fill this void, several studies have been recently focused on the identification of the peculiar proteomic profile of UCB-derived stem cells. Hereby, we concisely review recent proteomic surveys addressing UCB-derived stem and progenitor cells. Notably, comparative studies detected a wider spectrum of proteins in immature cells rather than in more differentiated populations, as if maturation events could represent a bottleneck to protein expression. Future research projects should try to shed light on these processes and their completion could pave the way for unprecedented treatments. © 2009 Elsevier B.V. All rights reserved. Source

Liumbruno G.,Italian National Blood Center | Liumbruno G.,Immunohematology and Transfusion Medicine Unit | D'Alessandro A.,Italian National Blood Center | D'Alessandro A.,University of Tuscia | And 2 more authors.
Critical Reviews in Oncology/Hematology | Year: 2010

Since the genomic era has not fully kept its promises, studies addressing the protein complement to the genome have been recently gaining momentum. Proteomics investigations could be potentially used from bench to bedside, in order to test the quality of collected blood components prior to or during storage. In parallel, proteomics could be used to verify the effects of the production and pathogen reduction processes of plasma derivatives and blood components on the protein fractions, or to reduce the effects of storage lesions. Another area of interest is represented by the discovery of peculiar biomarkers readily adoptable for targeted evaluation of blood-component integrity or functionality, as well as to assess the proliferative capacity of hematopoietic stem/progenitor cells. These accumulating basic research evidences will hopefully be accompanied by actual applications in routine clinical practice. Whether the costs of the needed facilities (instruments and trained personnel) will meet the current demand of the clinical market, proteomic-expert transfusionists will no longer only inform, but also perform a role in clinical routine. © 2010 Elsevier Ireland Ltd. Source

Fasano M.E.,Transplant Immunology Service | Rendine S.,Transplant Immunology Service | Rendine S.,University of Turin | Pasi A.,Foundation Medicine | And 24 more authors.
Tissue Antigens | Year: 2014

The killer cell immunoglobulin-like receptor (KIR)-human leukocyte antigen (HLA) interaction represents an example of genetic epistasis, where the concomitant presence of specific genes or alleles encoding receptor-ligand units is necessary for the activity of natural killer (NK) cells. Although KIR and HLA genes segregate independently, they co-evolved under environmental pressures to maintain particular KIR-HLA functional blocks for species survival. We investigated, in 270 Italian healthy individuals, the distribution of KIR and HLA polymorphisms in three climatic areas (from cold north to warm south), to verify their possible geographical stratification. We analyzed the presence of 13 KIR genes and genotyped KIR ligands belonging to HLA class I: HLA-C, HLA-B and HLA-A. We did not observe any genetic stratification for KIR genes and HLA-C ligands in Italy. By contrast, in a north-to-south direction, we found a decreasing trend for the HLA-A3 and HLA-A11 ligands (P=0.012) and an increasing trend for the HLA-B ligands carrying the Bw4 epitope (P=0.0003) and the Bw4 Ile80 epitope (P=0.0005). The HLA-A and HLA-B KIR ligands were in negative linkage disequilibrium (correlation coefficient -0.1211), possibly as a consequence of their similar function in inhibiting NK cells. The distribution of the KIR-HLA functional blocks was different along Italy, as we observed a north-to-south ascending trend for KIR3DL1, when coupled with HLA-B Bw4 ligands (P=0.0067) and with HLA-B Bw4 Ile80 (P=0.0027), and a descending trend for KIR3DL2 when coupled with HLA-A3 and HLA-A11 ligands (P=0.0044). Overall, people from South Italy preferentially use the KIR3DL1-HLA-B Bw4 functional unit, while those from the North Italy equally use both the KIR3DL2-HLA-A3/A11 and the KIR3DL1-HLA-B Bw4 functional units to fight infections. Thus, only KIR3DL receptors, which exert the unique role of microbial sensors through the specific D0 domain, and their cognate HLA-A and HLA-B ligands are selectively pressured in Italy according to geographical north-to-south distribution. © 2014 John Wiley & Sons A/S. Source

Matteocci A.,Immunohematology and Transfusion Medicine Unit | Pierelli L.,Immunohematology and Transfusion Medicine Unit | Pierelli L.,University of Rome La Sapienza
Vox Sanguinis | Year: 2014

Red blood cell (RBC) transfusions are a milestone in the treatment for sickle cell anaemia (SSA) and for thalassaemia. RBC alloimmunization remains a major challenge of chronic transfusion therapy, and it can lead to adverse life-threatening events. The alloimmunization risk could depend on multiple factors such as the number of transfusions and, most of all, the genetic background. Different ethnic groups are predisposed to immunization because of a significant degree of RBC antigenic mismatch between donor and recipient. There is no universal agreement and standards for the most appropriate selection of RBC units in chronically transfused subjects. Current practice only deals with compatibility of ABO, Rh and K antigens. Molecular RBC antigenic matching extended to other blood group systems is an innovative strategy to ensure a better quality and effectiveness of transfusion therapy. © 2013 International Society of Blood Transfusion. Source

Liumbruno G.,Italian National Blood Center | Liumbruno G.,Immunohematology and Transfusion Medicine Unit | D'Alessandro A.,Italian National Blood Center | D'Alessandro A.,University of Tuscia | And 2 more authors.
Journal of Proteomics | Year: 2010

Blood-related proteomics is an emerging field, recently gaining momentum. Indeed, a wealth of data is now available and a plethora of groups has contributed to add pieces to the jigsaw puzzle of protein complexity within plasma and blood cells. In this review article we purported to sail across the mare magnum of the actual knowledge in this research endeavour. The main strides in proteomic investigations on red blood cells, platelets, plasma and white blood cells are hereby presented in a chronological order. Moreover, a glance is given at prospective studies which promise to shift the focus of attention from the end product to its provider, the donor, in a sort of Kantian "Copernican revolution". A well-rounded portrait of the usefulness of proteomics in blood-related research is accurately given. In particular, proteomic tools could be adopted to follow the main steps of the blood-banking production processes (a comparison of collection methods, pathogen inactivation techniques, storage protocols). Thus proteomics has been recently transformed from a mere basic-research extremely-expensive toy into a dramatically-sensitive and efficient eye-lens to either delve into the depths of the molecular mechanisms of blood and blood components or to establish quality parameters in the blood-banking production chain totally anew. © 2009 Elsevier B.V. All rights reserved. Source

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