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GPI‐defective monocytes from paroxysmal nocturnal hemoglobinuria patients show impaired in vitro dendritic cell differentiation
Author(s) -
Ruggiero Giuseppina,
Terrazzano Giuseppe,
Becchimanzi Cristina,
Sica Michela,
Andretta Claudia,
Masci Anna Maria,
Racioppi Luigi,
Rotoli Bruno,
Zappacosta Serafino,
Alfinito Fiorella
Publication year - 2004
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.1203607
Subject(s) - paroxysmal nocturnal hemoglobinuria , biology , in vitro , immunology , dendritic cell , microbiology and biotechnology , monocyte , myeloid , immune system , genetics
Paroxysmal nocturnal hemoglobinuria (PNH) is a clonal, acquired hematopoietic disorder characterized by a phosphatidylinositol (PI) glycan‐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.