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Saint-Sauveur-en-Rue, France

Peyrard T.,National Institute of Blood Transfusion INTS
Immunohematology / American Red Cross | Year: 2013

LAN (Langereis) was officially recognized by the International Society of Blood Transfusion in 2012 as being the 33rd human blood group system. It consists of one single high-prevalence antigen,Lan (LANl). The ABCB6 protein is the carrier of the Lan blood group antigen. The ABCB6 gene (chromosome 2q36, 19 exons)encodes the ABCB6 polypeptide (ATP-binding cassette protein,subfamily B, member 6), known as a porphyrin transporter.The exceptional Lan- people do not express ABCB6 (Lan null phenotype), owing to several different molecular mechanisms affecting ABCB6: frameshift leading to a premature stop codon(deletion, insertion, or nonsense mutation of nucleotides);missense mutation; or intronic mutation responsible for RNA splicing defect. Despite the Lan antigen's being reported to play a key role in erythropoiesis and detoxification of cells, Lan people do not appear to demonstrate susceptibility to any disease or seemingly physiologic disorder. Anti-Lan has been described as having variable clinical significance, either for hemolytic transfusion reactions (none to severe) or hemolytic disease of the fetus and newborn (none to mild). Despite challenging conditions caused by the scarcity of Lan- donors worldwide, Lan- blood should ideally be given to patients with anti-Lan, especially those with a high-titer antibody. Source


Garraud O.,National Institute of Blood Transfusion INTS | Garraud O.,Jean Monnet University | Cognasse F.,Jean Monnet University | Tissot J.-D.,Red Cross | And 9 more authors.
Blood Transfusion | Year: 2016

Platelet concentrates account for near 10% of all labile blood components but are responsible for more than 25% of the reported adverse events. Besides factors related to patients themselves, who may be particularly at risk of side effects because of their underlying illness, there are aspects of platelet collection and storage that predispose to adverse events. Platelets for transfusion are strongly activated by collection through disposal equipment, which can stress the cells, and by preservation at 22°C with rotation or rocking, which likewise leads to platelet activation, perhaps more so than storage at 4°C. Lastly, platelets constitutively possess a very large number of bioactive components that may elicit pro-inflammatory reactions when infused into a patient. This review aims to describe approaches that may be crucial to minimising side effects while optimising safety and quality. We suggest that platelet transfusion is complex, in part because of the complexity of the "material" itself: platelets are highly versatile cells and the transfusion process adds a myriad of variables that present many challenges for preserving basal platelet function and preventing dysfunctional activation of the platelets. The review also presents information showing - after years of exhaustive haemovigilance - that whole blood buffy coat pooled platelet components are extremely safe compared to the gold standard (i.e. apheresis platelet components), both in terms of acquired infections and of immunological/inflammatory hazards. © SIMTI Servizi Srl. Source


Helias V.,National Institute of Blood Transfusion INTS | Saison C.,National Institute of Blood Transfusion INTS | Peyrard T.,National Institute of Blood Transfusion INTS | Peyrard T.,National Reference Center for Blood Groups | And 5 more authors.
Human Mutation | Year: 2013

KLF1 encodes an erythroid transcription factor, whose essential function in erythropoiesis has been demonstrated by extensive studies in mouse models. The first reported mutations in human KLF1 were found in individuals with a rare and asymptomatic blood type called In(Lu). Here, we show that KLF1 haploinsufficiency is responsible for the In(Lu) blood type, after redefining this peculiar blood type using flow cytometry to quantify the levels of BCAM and CD44 on red blood cells. We found 10 (seven novel) heterozygous KLF1 mutations responsible for the In(Lu) blood type. Although most were obligate loss-of-function mutations due to the truncation of the DNA-binding domain of KLF1, three were missense mutations that were located in its DNA-binding domain and impaired the transactivation capacity of KLF1 in vitro. We further showed that the levels of the hemoglobin variants HbF and HbA2 were increased in the In(Lu) blood type, albeit differently. The levels of the membrane glycoproteins BCAM and CD44 were also differently reduced on In(Lu) red blood cells. This biochemical and genetic analysis of the In(Lu) blood type tackles the phenotypic outcome of haploinsufficiency for a transcription factor. © 2012 Wiley Periodicals, Inc. Source


Ballif B.A.,University of Vermont | Helias V.,National Institute of Blood Transfusion INTS | Peyrard T.,National Institute of Blood Transfusion INTS | Peyrard T.,National Reference Center for Blood Groups | And 9 more authors.
EMBO Molecular Medicine | Year: 2013

Here, we report the biochemical and genetic basis of the Vel blood group antigen, which has been a vexing mystery for decades, especially as anti-Vel regularly causes severe haemolytic transfusion reactions. The protein carrying the Vel blood group antigen was biochemically purified from red blood cell membranes. Mass spectrometry-based de novo peptide sequencing identified this protein to be small integral membrane protein 1 (SMIM1), a previously uncharacterized single-pass membrane protein. Expression of SMIM1 cDNA in Vel- cultured cells generated anti-Vel cell surface reactivity, confirming that SMIM1 encoded the Vel blood group antigen. A cohort of 70 Vel- individuals was found to be uniformly homozygous for a 17 nucleotide deletion in the coding sequence of SMIM1. The genetic homogeneity of the Vel- blood type, likely having a common origin, facilitated the development of two highly specific DNA-based tests for rapid Vel genotyping, which can be easily integrated into blood group genotyping platforms. These results answer a 60-year-old riddle and provide tools of immediate assistance to all clinicians involved in the care of Vel- patients. © 2013. Source


Helias V.,National Institute of Blood Transfusion INTS | Saison C.,National Institute of Blood Transfusion INTS | Ballif B.A.,University of Vermont | Peyrard T.,National Institute of Blood Transfusion INTS | And 15 more authors.
Nature Genetics | Year: 2012

The human ATP-binding cassette (ABC) transporter ABCB6 has been described as a mitochondrial porphyrin transporter essential for heme biosynthesis, but it is also suspected to contribute to anticancer drug resistance, as do other ABC transporters located at the plasma membrane. We identified ABCB6 as the genetic basis of the Lan blood group antigen expressed on red blood cells but also at the plasma membrane of hepatocellular carcinoma (HCC) cells, and we established that ABCB6 encodes a new blood group system (Langereis, Lan). Targeted sequencing of ABCB6 in 12 unrelated individuals of the Lan(-) blood type identified 10 different ABCB6 null mutations. This is the first report of deficient alleles of this human ABC transporter gene. Of note, Lan(-) (ABCB6 -/-) individuals do not suffer any clinical consequences, although their deficiency in ABCB6 may place them at risk when determining drug dosage. © 2012 Nature America, Inc. All rights reserved. Source

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