GPI-defective monocytes from paroxysmal nocturnal hemoglobinuria patients show impaired in vitro dendritic cell differentiation

Giuseppina Ruggiero, Giuseppe Terrazzano, Cristina Becchimanzi, Michela Sica, Claudia Andretta, Anna Maria Masci, Luigi Racioppi, Bruno Rotoli, Serafino Zappacosta, Fiorella Alfinito

Research output: Contribution to journalArticlepeer-review


Paroxysmal nocturnal hemoglobinuria (PNH) is a clonal, acquired hematopoietic disorder characterized by a phosphatidylinositol (PI) gly-can-A gene mutation, which impairs the synthesis of the glycosyl-PI (GPI) anchor, thus causing the absence of all GPI-linked proteins on the membrane of the clonal-defective cells. The presence of a consistent GPI-defective monocyte compartment is a common feature in PNH patients. To investigate the functional behavior of this population, we analyzed its in vitro differentiation ability toward functional dendritic cells (DCs). Our data indicate that GPI-defective monocytes from PNH patients are unable to undergo full DC differentiation in vitro after granulocyte macrophage-colony stimulating factor and recombinant interleukin (IL)-4 treatment. In this context, the GPI-defective DC population shows mannose receptor expression, high levels of the CD86 molecule, and impaired CD1a up-regulation. The analysis of lipopolysaccharide and CD40-dependent, functional pathways in these DCs revealed a strong decrease in tumor necrosis factor α and IL-12 production. Finally, GPI-defective DCs showed a severe impairment in delivering accessory signals for T cell receptor-dependent T cell proliferation.

Original languageEnglish
Pages (from-to)634-640
Number of pages7
JournalJournal of Leukocyte Biology
Issue number3
Publication statusPublished - Sep 2004


  • Accessory signals
  • Cytokine secretion
  • GPI-linked molecules

ASJC Scopus subject areas

  • Cell Biology


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