Correlation of red cell hemolysis with (a) G-6-PD type in two female G-6-PD mosaics with PNH and with (b) erythrocyte acetylcholinesterase deficiency, provides strong evidence for the clonal theory of PNH.3.
Correlation of red cell hemolysis with (a) G-6-PD type in two female G-6-PD mosaics with PNH and with (b) erythrocyte acetylcholinesterase deficiency, provides strong evidence for the clonal theory of PNH.3.
Major blood group-compatible erythrocytes from a patient with paroxysmal nocturnal hemoglobinuria had the same shortened survival in the C3-deficient patient as in a normal control.
A soluble form of the glycolipid-anchored receptor for urokinase-type plasminogen activator is secreted from peripheral blood leukocytes from patients with paroxysmal nocturnal hemoglobinuria.
The presence in plasma from PNH patients of such a secreted, hydrophilic form of uPAR lends support to the hypothesis that the lesion underlying the PNH disorder resides either in glycolipid biosynthesis or in the function of an as-yet-unidentified transamidating enzyme assumed to cleave and assemble the truncated uPAR with the preformed glycolipid moiety.
Chem., in press) we characterized the biosynthesis of putative Man-containing GPI anchor precursors in normal peripheral blood lymphocytes and investigated assembly of these intracellular GPI intermediates in CD48- affected and CD48+ unaffected T and natural killer cell lines of PNH patients.
Analyses of greater than 98% surface DAF-negative PMN and MNC from a patient with PNH III erythrocytes showed precursor DAF protein approximately 3 kD smaller in each cell type than in normal cells.
In addition, the level of LAM-1 expression by lymphocytes and neutrophils from two patients with paroxysmal nocturnal hemoglobinuria, a disorder in which linkage of phosphatidylinositol anchors to proteins is defective, was similar to that of normal controls.
The neutrophils of these two individuals were not able to bind dimeric immunoglobulin G. However, their cells had a normal expression of other phosphatidylinositol (PI)-linked membrane glycoprotein (CD24, CD67, and CLB gran/5 antigens), ruling out the existence of a PI-linkage defect, such as paroxysmal nocturnal hemoglobinuria.
The neutrophils of these two individuals were not able to bind dimeric immunoglobulin G. However, their cells had a normal expression of other phosphatidylinositol (PI)-linked membrane glycoprotein (CD24, CD67, and CLB gran/5 antigens), ruling out the existence of a PI-linkage defect, such as paroxysmal nocturnal hemoglobinuria.
COS cells transfected with the CD14 cDNA released virtually all CD14 protein in soluble form following treatment with glycosyl phosphatidylinositol-specific phospholipase C, and CD14 immunoreactivity was absent from the affected monocytes of a patient with paroxysmal nocturnal hemoglobinuria (PNH).
COS cells transfected with the CD14 cDNA released virtually all CD14 protein in soluble form following treatment with glycosyl phosphatidylinositol-specific phospholipase C, and CD14 immunoreactivity was absent from the affected monocytes of a patient with paroxysmal nocturnal hemoglobinuria (PNH).
The results suggest that the primary molecular defect underlying the clinical manifestations of PNH may be the lack of the membrane-associated DAF protein and that the abnormal cells may also exhibit impaired CR1 function.
These cells were not susceptible to complement-mediated lysis in acidified human serum, whereas PNH erythrocytes and Pronase-treated human erythrocytes (which lack DAF and CR1 activities) were lysed by this treatment.
In contrast, specific immune precipitates of PNH-E from three patients show C3bR but are deficient in DAF; type II PNH-E are relatively deficient and type III PNH-E are totally deficient in DAF.
The hematologic disorder paroxysmal nocturnal hemoglobinuria (PNH) arises from a somatic mutation within the Piga gene important for the biosynthesis of glycosylphosphatidylinositol (GPI) anchors.
A GPI-anchoring deficient complement-sensitive B-cell line derived from a PNH patient was successfully transduced with CD59-TM, resulting in surface expression of the protein.
Moreover, they lack surface expression of complement regulatory proteins such as DAF (CD55) and CD59, that are the most important glycosylphosphatidylinositol (GPI)-anchored membrane proteins defective in haemopoietic cells of patients with PNH.
Moreover, they lack surface expression of complement regulatory proteins such as DAF (CD55) and CD59, that are the most important glycosylphosphatidylinositol (GPI)-anchored membrane proteins defective in haemopoietic cells of patients with PNH.