title: Are polymorphisms of the immunoregulatory factor CD40LG implicated in acute transfusion reactions?
abstract: The CD40 ligand (CD40L/CD154), a member of TNF superfamily, is notably expressed on activated CD4+ T-cells and stimulated platelets. CD40L is linked to a variety of pathologies and to acute transfusion reactions (ATR). Mutations in this gene (CD40LG) lead to X-linked hyper-IgM syndrome. Some CD40LG polymorphisms are associated with variable protein expression. The rationale behind this study is that CD40L protein has been observed to be involved in ATR. We wondered whether genetic polymorphisms are implicated. We investigated genetic diversity in the CD40LG using DHPLC and capillary electrophoresis for screening and genotyping (n = 485 French and Tunisian blood donors). We identified significant difference in the CD40LG linkage pattern between the two populations. Variant minor alleles were significantly over-represented in Tunisian donors (P<0.0001 to 0.0270). We found higher heterogeneity in the Tunisian, including three novel low frequency variants. As there was not a particular pattern of CD40LG in single apheresis donors whose platelet components induced an ATR, we discuss how this information may be useful for future disease association studies on CD40LG.
authors.affiliation: 1] University of Lyon GIMAP-EA3064, Saint-Etienne, France [2] French Blood Establishment, EFS Auvergne-Loire, Saint-Etienne, France.
authors.forename: Chaker
authors.initials: C
authors.lastname: Aloui
authors.affiliation: University of Lyon GIMAP-EA3064, Saint-Etienne, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Sut
authors.affiliation: 1] University of Lyon GIMAP-EA3064, Saint-Etienne, France [2] French Blood Establishment, EFS Auvergne-Loire, Saint-Etienne, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Prigent
authors.affiliation: French Blood Establishment, EFS Auvergne-Loire, Saint-Etienne, France.
authors.forename: Jocelyne
authors.initials: J
authors.lastname: Fagan
authors.affiliation: 1] University of Lyon GIMAP-EA3064, Saint-Etienne, France [2] French Blood Establishment, EFS Auvergne-Loire, Saint-Etienne, France.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Cognasse
authors.affiliation: Department of Molecular Genetics, Saint Etienne University Hospital, France.
authors.forename: Viviana
authors.initials: V
authors.lastname: Granados-Herbepin
authors.affiliation: Department of Molecular Genetics, Saint Etienne University Hospital, France.
authors.forename: Renaud
authors.initials: R
authors.lastname: Touraine
authors.affiliation: University of Lyon GIMAP-EA3064, Saint-Etienne, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Pozzetto
authors.affiliation: University of Monastir, Tunisia.
authors.forename: Mahjoub
authors.initials: M
authors.lastname: Aouni
authors.affiliation: University of Monastir, Tunisia.
authors.forename: Chedlia
authors.initials: C
authors.lastname: Fendri
authors.affiliation: Blood Bank of Monastir, F. Bourguiba University Hospital, Tunisia.
authors.forename: Mohsen
authors.initials: M
authors.lastname: Hassine
authors.affiliation: Regional Centre of Transfusion of Sousse, F. Hached University Hospital, Tunisia.
authors.forename: Tahar
authors.initials: T
authors.lastname: Chakroun
authors.affiliation: Regional Centre of Transfusion of Sousse, F. Hached University Hospital, Tunisia.
authors.forename: Saloua
authors.initials: S
authors.lastname: Jemni-Yacoub
authors.affiliation: 1] University of Lyon GIMAP-EA3064, Saint-Etienne, France [2] French Blood Establishment, EFS Auvergne-Loire, Saint-Etienne, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Garraud
authors.affiliation: 1] University of Lyon GIMAP-EA3064, Saint-Etienne, France [2] French Blood Establishment, EFS Auvergne-Loire, Saint-Etienne, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Laradi
mesh_terms: D000328:Adult; D000483:Alleles; D023201:CD40 Ligand / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D007155:Immunologic Factors / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D065227:Transfusion Reaction / Q000235:genetics*; D055815:Young Adult
chemical_list: D007155:Immunologic Factors; D023201:CD40 Ligand