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

Roberta Rizzo, Valentina Audrito, Paola Vacca, Davide Rossi, Davide Brusa, Marina Stignani, Daria Bortolotti, Giovanni D'Arena, Marta Coscia, Luca Laurenti, Francesco Forconi, Gianluca Gaidano, Maria Cristina Mingari, Lorenzo Moretta, Fabio Malavasi, Silvia Deaglio

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)888-896
Number of pages9
JournalHaematologica
Volume99
Issue number5
DOIs
Publication statusPublished - May 1 2014

ASJC Scopus subject areas

  • Hematology
  • Medicine(all)

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