title: HLA-G is a component of the chronic lymphocytic leukemia escape repertoire to generate immune suppression: impact of the HLA-G 14 base pair (rs66554220) polymorphism.
abstract: This work investigates the possibility that HLA-G, a molecule modulating innate and adaptive immunity, is part of an immune escape strategy of chronic lymphocytic leukemia cells. A 14 base pair insertion/deletion polymorphism (rs66554220) in the 3'-untranslated region of HLA-G influences mRNA stability and protein expression. The analysis of a cohort of patients with chronic lymphocytic leukemia confirmed that del/del individuals are characterized by higher levels of surface and soluble HLA-G than subjects with the other two genotypes. In line with its role in immunomodulation, the percentage of regulatory T lymphocytes is higher in del/del patients than in patients with the other genotypes and correlates with the amounts of surface or soluble HLA-G. Furthermore, addition of sHLA-G-rich plasma from patients with chronic lymphocytic leukemia induces natural killer cell apoptosis and impairs natural killer cell lysis, with effects proportional to the amount of soluble HLA-G added. Lastly, the presence of an HLA-G 14 base pair polymorphism is of prognostic value, with del/del patients showing reduced overall survival, as compared to those with other genotypes. These results suggest that: (i) the HLA-G 14 base pair polymorphism influences the levels of surface and soluble HLA-G expression, and (ii) the over-expression of HLA-G molecules contributes to creating tolerogenic conditions.
authors.affiliation: silvia.deaglio@unito.it or roberta.rizzo@unife.it.
authors.forename: Roberta
authors.initials: R
authors.lastname: Rizzo
authors.forename: Valentina
authors.initials: V
authors.lastname: Audrito
authors.forename: Paola
authors.initials: P
authors.lastname: Vacca
authors.forename: Davide
authors.initials: D
authors.lastname: Rossi
authors.forename: Davide
authors.initials: D
authors.lastname: Brusa
authors.forename: Marina
authors.initials: M
authors.lastname: Stignani
authors.forename: Daria
authors.initials: D
authors.lastname: Bortolotti
authors.forename: Giovanni
authors.initials: G
authors.lastname: D'Arena
authors.forename: Marta
authors.initials: M
authors.lastname: Coscia
authors.forename: Luca
authors.initials: L
authors.lastname: Laurenti
authors.forename: Francesco
authors.initials: F
authors.lastname: Forconi
authors.forename: Gianluca
authors.initials: G
authors.lastname: Gaidano
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Mingari
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Moretta
authors.forename: Fabio
authors.initials: F
authors.lastname: Malavasi
authors.forename: Silvia
authors.initials: S
authors.lastname: Deaglio
mesh_terms: D005260:Female; D015870:Gene Expression; D059951:HLA-G Antigens / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D016130:Immunophenotyping; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000276:immunology* / Q000401:mortality; D018655:Lymphocyte Count; D008297:Male; D011110:Polymorphism, Genetic; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D019139:Tumor Escape / Q000235:genetics* / Q000276:immunology*
chemical_list: D059951:HLA-G Antigens; D012333:RNA, Messenger