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Decreased prion protein expression in human peripheral blood leucocytes from patients with paroxysmal nocturnal haemoglobinuria
Author(s) -
Dürig Jan,
Giese Armin,
Schmücker Ute,
Kretzschmar Hans A.,
Dührsen Ulrich
Publication year - 2001
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.2001.02602.x
Subject(s) - monoclonal antibody , flow cytometry , glycoprotein , pathogenesis , cell , lymphocyte , paroxysmal nocturnal hemoglobinuria , microbiology and biotechnology , monoclonal , chemistry , immunology , antibody , biology , biochemistry
The cellular isoform of the prion protein (PrP C ) is a cell surface glycoprotein attached to the outer leaflet of the plasma membrane by a glycosylphosphatidyl‐inositol (GPI) anchor. PrP C is involved in the pathogenesis of prion diseases and has recently been shown to play a role in haemopoietic cell activation and proliferation. We have used the PrP C ‐specific monoclonal antibody (mAb) 3F4 in a flow cytometry approach to analyse the constitutive expression of PrP C on human peripheral blood (PB) cell populations from patients with paroxysmal nocturnal haemoglobinuria (PNH), which are characterized by a deficiency of GPI‐linked cell surface proteins. Comparable PrP C expression levels ( P > 0·05), quantified as mean fluorescent intensity, were measured on lymphocytes isolated from normal donors ( n = 10) and patients with PNH ( n = 5), whereas PNH PB monocytes and granulocytes exhibited substantially lower PrP C surface immunoreactivity than their normal counterparts ( P < 0·05). More detailed histogram analyses of the PNH PB leucocytes revealed that PrP C was absent in PNH granulocytes, but was normally expressed in lymphocytes from four out of five patients. However, in one patient a bimodal distribution of 3F4 mAb staining was observed, indicating the presence of a PrP C ‐deficient lymphocyte subpopulation. In conclusion, our results show that PNH haemopoietic cells are deficient in cell surface‐bound PrP C .