scholarly journals Inhibitors of complement derived from the erythrocyte membrane in paroxysmal nocturnal hemoglobinuria

Blood ◽  
1980 ◽  
Vol 55 (5) ◽  
pp. 772-776 ◽  
Author(s):  
C Chua ◽  
EM Hoffmann ◽  
JP Adams ◽  
WF Rosse
Keyword(s):  
Erythrocyte Membrane ◽  
Complement Activation ◽  
Inhibitory Activity ◽  
Paroxysmal Nocturnal Hemoglobinuria ◽  
Cell Lysis ◽  
Red Cells ◽  
Cobra Venom ◽  
Normal Cells ◽  
Complement Lysis

Abstract Extracts of the membranes of normal red cells and red cells from all subpopulations of paroxysmal nocturnal (PNH) red cells inhibited antibody-mediated complement activation. These extracts were shown to accelerate decay of the complement complex. C42, and the relative amount of inhibitory activity was similar in normal and PNH membranes. Inhibitors derived from normal red cells markedly decreased lysis of both PNH and normal cells when antibody was present in excess and complement was limiting. These same inhibitors decreased PNH cell lysis to a much lesser degree when complement was activated with cobra venom or acidified serum. The susceptibility of the PNH cell to complement lysis because of an increased fixation of C3 to its membrane is not due to a difference in membrane-associated accelerator of the decay of the C42 complex.

scholarly journals Inhibitors of complement derived from the erythrocyte membrane in paroxysmal nocturnal hemoglobinuria

Blood ◽  
1980 ◽  
Vol 55 (5) ◽  
pp. 772-776
Author(s):  
C Chua ◽  
EM Hoffmann ◽  
JP Adams ◽  
WF Rosse
Keyword(s):  
Erythrocyte Membrane ◽  
Complement Activation ◽  
Inhibitory Activity ◽  
Paroxysmal Nocturnal Hemoglobinuria ◽  
Cell Lysis ◽  
Red Cells ◽  
Cobra Venom ◽  
Normal Cells ◽  
Complement Lysis

Extracts of the membranes of normal red cells and red cells from all subpopulations of paroxysmal nocturnal (PNH) red cells inhibited antibody-mediated complement activation. These extracts were shown to accelerate decay of the complement complex. C42, and the relative amount of inhibitory activity was similar in normal and PNH membranes. Inhibitors derived from normal red cells markedly decreased lysis of both PNH and normal cells when antibody was present in excess and complement was limiting. These same inhibitors decreased PNH cell lysis to a much lesser degree when complement was activated with cobra venom or acidified serum. The susceptibility of the PNH cell to complement lysis because of an increased fixation of C3 to its membrane is not due to a difference in membrane-associated accelerator of the decay of the C42 complex.

scholarly journals Differences in the terminal steps of complement lysis of normal and paroxysmal nocturnal hemoglobinuria red cells

Blood ◽  
1978 ◽  
Vol 51 (2) ◽  
pp. 325-330 ◽  
Author(s):  
TA Rouault ◽  
WF Rosse ◽  
S Bell ◽  
J Shelburne
Keyword(s):  
Paroxysmal Nocturnal Hemoglobinuria ◽  
Alternative Pathway ◽  
Red Cells ◽  
Cobra Venom ◽  
Classical Pathway ◽  
Normal Cells ◽  
Cobra Venom Factor ◽  
Significant Difference ◽  
Complement Lysis

The number of microscopically visible lesions produced on the membrane for a given degree of lysis on normal cells as on PNH cells. Since complement lesions were not formed until C8 or C9 was incorporated into the complement sequence, the results suggest that increased lysis of red cells in PNH is due at least in part to more efficient penetration of the PNH membrane by the terminal lytic sequence of complement. Furthermore, the efficiency of the terminal lytic sequence in the lysis of PNH cells when complement was activated by the alternative pathway and the classical pathway was analyzed. There was no significant difference (p less than 0.01) in the number of lesion present at an equivalent degree of lysis when initiated by antibody, cobra venom factor, or acidification. Thus, the efficiency of the terminal lytic sequence does not vary with different modes of activation.

scholarly journals Differences in the terminal steps of complement lysis of normal and paroxysmal nocturnal hemoglobinuria red cells

Blood ◽  
1978 ◽  
Vol 51 (2) ◽  
pp. 325-330 ◽  
Author(s):  
TA Rouault ◽  
WF Rosse ◽  
S Bell ◽  
J Shelburne
Keyword(s):  
Paroxysmal Nocturnal Hemoglobinuria ◽  
Alternative Pathway ◽  
Red Cells ◽  
Cobra Venom ◽  
Classical Pathway ◽  
Normal Cells ◽  
Cobra Venom Factor ◽  
Significant Difference ◽  
Complement Lysis

Abstract The number of microscopically visible lesions produced on the membrane for a given degree of lysis on normal cells as on PNH cells. Since complement lesions were not formed until C8 or C9 was incorporated into the complement sequence, the results suggest that increased lysis of red cells in PNH is due at least in part to more efficient penetration of the PNH membrane by the terminal lytic sequence of complement. Furthermore, the efficiency of the terminal lytic sequence in the lysis of PNH cells when complement was activated by the alternative pathway and the classical pathway was analyzed. There was no significant difference (p less than 0.01) in the number of lesion present at an equivalent degree of lysis when initiated by antibody, cobra venom factor, or acidification. Thus, the efficiency of the terminal lytic sequence does not vary with different modes of activation.

scholarly journals Fetal hemoglobin in paroxysmal nocturnal hemoglobinuria (PNH): evidence for derivation of HbF-containing erythrocytes (F cells) from the PNH clone as well as from normal hemopoietic stem cell lines

Blood ◽  
1978 ◽  
Vol 52 (4) ◽  
pp. 740-749 ◽  
Author(s):  
T Papayannopoulou ◽  
W Rosse ◽  
G Stamatoyannopoulos
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Lines ◽  
Whole Blood ◽  
Paroxysmal Nocturnal Hemoglobinuria ◽  
Red Cells ◽  
Hemopoietic Stem Cell ◽  
Normal Cells ◽  
F Cells ◽  
Stem Cell Lines

Abstract The cellular distribution of HbF was studied in nine patients with paroxysmal nocturnal hemoglobinuria (PNH) by measuring the level of HbF and determining the number of HbF-containing red cells (F cells) in whole blood and in the population of normal cells obtained after immune lysis of the abnormal erythrocytes. The amounts of HbF and the F cell frequencies found in the normal red cells were strikingly similar to the values seen in whole blood. The observed frequencies of F cells in normal cells best fitted those expected under the assumption that the F cells arise equally from normal hemopoietic stem cells and from the stem cells with the PNH defect. Since PNH appears to be a clonal hemopoietic stem cell disorder, this evidence argues against a derivation of F cells from distinct pluripotent stem cell lines.

scholarly journals Case Report: Paroxysmal nocturnal hemoglobinuria in a woman heterozygous for G6PD A-

F1000Research ◽  
2014 ◽  
Vol 3 ◽  
pp. 194
Author(s):  
Nieves Perdigones ◽  
Mariela Morales ◽  
Philip Mason ◽  
Monica Bessler
Keyword(s):  
X Chromosome ◽  
Complement Activation ◽  
Paroxysmal Nocturnal Hemoglobinuria ◽  
Somatic Mutations ◽  
Pentose Phosphate ◽  
Loss Of Function ◽  
Cell Surface Antigens ◽  
Class A ◽  
Glucose 6 Phosphate Dehydrogenase ◽  
Complement Lysis

We describe a case of paroxysmal nocturnal hemoglobinuria (PNH) in a woman who is heterozygous for the glucose-6-phosphate dehydrogenase A-   (G6PDA-) allele. PNH is associated with one or more clones of cells that lack complement inhibition due to loss of function somatic mutations in thePIGAgene. PIGAencodes the enzyme phosphatidylinositol glycan anchor biosynthesis, class A, which catalyses the first step of glycosylphosphatidylinisotol (GPI)  anchor synthesis. Two GPI anchored red cell surface antigens regulate complement lysis. G6PD catalyses the first step of the pentose phosphate pathway and enzyme variants, frequent in some populations have been because they confer resistance to malaria, are associated with hemolysis in the presence of oxidizing agents including several drugs. The patient had suffered a hemolytic attack after taking Bactrim, a drug that precipitates hemolysis in G6PD deficient individuals. Since bothG6PDandPIGAare X-linked we hypothesized that the PIGA mutation was on the X-chromosome carrying the G6PDA- allele. Investigations showed that in fact the PIGA mutation was on the X-chromosome carrying the normalG6PD Ballele. We speculate that complement activation on G6PD A- red cells exposed to Bactrim might have triggered complement activation inducing the lysis of G6PD B PNH Type II red blood cells or that the patient may have had a PNH clone expressing G6PDA- at the time of the hemolytic episode.

scholarly journals Two populations of granulocytes in paroxysmal nocturnal hemoglobinuria

Blood ◽  
1979 ◽  
Vol 53 (5) ◽  
pp. 928-934 ◽  
Author(s):  
M Stern ◽  
WF Rosse
Keyword(s):  
Stem Cell ◽  
Paroxysmal Nocturnal Hemoglobinuria ◽  
Complement C3 ◽  
51Cr Release ◽  
Normal Cells ◽  
Lytic Action ◽  
The Third ◽  
Two Populations ◽  
Complement Lysis ◽  
Third Component Of Complement

Abstract The granulocytes in paroxysmal nocturnal hemoglobinuria (PNH) are defective, and the defect is similar to that previously described for the PNH erythrocyte. Using anti-I antibody to activate complement and 51Cr release to detect cell lysis, we found two populations of granulocytes that differed in their susceptibility to lysis by complement in 5 of 6 patients. A proportion of the cells were lysed by one-fifteenth to one-twentieth the amount of complement required to lyse normal cells; the remainder of the granulocytes appeared to be normal in their susceptibility to the lytic action of complement. The binding of the third component of complement (C3) to PNH granulocytes was at least twice that bound to normal cells, even though the binding of antibody was the same for normal and PNH cells. This suggests that the binding of C3 and probably the efficiency of the terminal steps of complement lysis are increased in the abnormal PHN granulocyte. These defects affect only a portion of the granulocytes, thus suggesting that the disorder is a clonal stem cell abnormality.

scholarly journals Quantitative Studies on the Sensitivity to Complement Lysis of Red Cells Treated With Thiol-reactive Reagents

Blood ◽  
1971 ◽  
Vol 37 (4) ◽  
pp. 454-462 ◽  
Author(s):  
NANCY W. STEAD ◽  
WENDELL F. ROSSE
Keyword(s):  
Reduced Glutathione ◽  
Acetylcholinesterase Activity ◽  
Red Cells ◽  
Percentage Increase ◽  
Concomitant Increase ◽  
Short Term ◽  
Normal Cells ◽  
Quantitative Studies ◽  
Term Storage ◽  
Complement Lysis

Abstract The effect of reduced glutathione on the complement sensitivity of normal and paroxysmal nocturnal hemoglobinuria (PNH) red cells was determined quantitatively. The susceptibility to complement lysis was increased in normal and complement-sensitive and complement-insensitive PNH cells; the percentage increase in susceptibility was inversely related to the initial complement-sensitivity. P-chloromercuribenzene sulfonate (PCMBS) likewise increased the sensitivity of normal cells to lysis by complement; the effect with both compounds appeared to be due to reaction with membrane thiol groups. GSH-treated normal cells were similar to PNH cells in that the susceptibility to immune lysis occurred without concomitant increase in fixation of antibody or first component of complement. GSH-treated normal cells differed from PNH cells in that the membrane acetylcholinesterase activity was normal and the cells were not stable during preparation and short-term storage.

scholarly journals The use of monoclonal antibodies and flow cytometry in the diagnosis of paroxysmal nocturnal hemoglobinuria

Blood ◽  
1996 ◽  
Vol 87 (12) ◽  
pp. 5332-5340 ◽  
Author(s):  
SE Hall ◽  
WF Rosse
Keyword(s):  
Flow Cytometry ◽  
Monoclonal Antibodies ◽  
Detailed Analysis ◽  
Paroxysmal Nocturnal Hemoglobinuria ◽  
Red Cells ◽  
Partial Deficiency ◽  
Complement Lysis

We have characterized the erythrocytes, granulocytes, and platelets of 54 patients with paroxysmal nocturnal hemoglobinuria (PNH) with antibodies to glycosylphosphatidylinositol-anchored proteins (anti- CD55, anti-CD59, and anti-CD16) and flow cytometry to establish the usefulness of this technique in the diagnosis of this disorder. All patients demonstrated either completely (PNH III) or partially (PNH II) deficient red cells and granulocytes. Anti-CD59 best demonstrated PNH II red cells, which were present in 50% of the patients. The proportion of abnormal granulocytes was usually greater than the proportion of abnormal red cells; 37% of the patients had >80% abnormal granulocytes. Anti-CD55 did not delineate the erythrocyte populations as well as did anti-CD59. Either anti-CD55 or anti-CD59 could be used equally well to analyze granulocytes; anti-CD16 did not demonstrate cells of partial deficiency. Platelets could not be used for detailed analysis as the normal and abnormal populations were not well distinguished. Flow cytometry of erythrocytes using anti-CD59 or of granulocytes using either anti-CD55 or anti-CD59 provides the most accurate technique for the diagnosis of paroxysmal nocturnal hemoglobinuria; it is clearly more specific, more quantitative, and more sensitive than the tests for PNH that depend upon hemolysis by complement (the acidified serum lysis [Ham] test, the sucrose lysis test, and the complement lysis sensitivity [CLS] test).

scholarly journals Case Report: Paroxysmal nocturnal hemoglobinuria in a woman heterozygous for G6PD A-

F1000Research ◽  
2014 ◽  
Vol 3 ◽  
pp. 194 ◽  
Author(s):  
Nieves Perdigones ◽  
Mariela Morales ◽  
Philip Mason ◽  
Monica Bessler
Keyword(s):  
X Chromosome ◽  
Complement Activation ◽  
Paroxysmal Nocturnal Hemoglobinuria ◽  
Somatic Mutations ◽  
Pentose Phosphate ◽  
Loss Of Function ◽  
Cell Surface Antigens ◽  
Class A ◽  
Glucose 6 Phosphate Dehydrogenase ◽  
Complement Lysis

We describe a case of paroxysmal nocturnal hemoglobinuria (PNH) in a woman who is heterozygous for the glucose-6-phosphate dehydrogenase A-   (G6PDA-) allele. PNH is associated with one or more clones of cells that lack complement inhibition due to loss of function somatic mutations in thePIGAgene. PIGAencodes the enzyme phosphatidylinositol glycan anchor biosynthesis, class A, which catalyses the first step of glycosylphosphatidylinisotol (GPI)  anchor synthesis. Two GPI anchored red cell surface antigens regulate complement lysis. G6PD catalyses the first step of the pentose phosphate pathway and enzyme variants, frequent in some populations have been selected because they confer resistance to malaria, are associated with hemolysis in the presence of oxidizing agents including several drugs. The patient had suffered a hemolytic attack after taking co-trimoxazole, a drug that precipitates hemolysis in G6PD deficient individuals. Since bothG6PDandPIGAare X-linked we hypothesized that thePIGAmutation was on the X-chromosome carrying theG6PDA- allele. Investigations showed that in fact thePIGAmutation was on the X-chromosome carrying the normalG6PD Ballele. We speculate that complement activation onG6PD A- red cells exposed to Bactrim might have triggered complement activation inducing the lysis ofG6PD BPNH Type II red blood cells or that the patient may have had a PNH clone expressingG6PDA-at the time of the hemolytic episode.

scholarly journals Leukocyte Antigen-Antibody Reaction and Lysis of Paroxysmal Nocturnal Hemoglobinuria Erythrocytes

Blood ◽  
1970 ◽  
Vol 36 (3) ◽  
pp. 334-336 ◽  
Author(s):  
GIROLAMO SIRCHIA ◽  
SOLDANO FERRONE ◽  
FRANCESCO MERCURIALI
Keyword(s):  
Paroxysmal Nocturnal Hemoglobinuria ◽  
Cell Lysis ◽  
Red Cells ◽  
Clinical Implications ◽  
Specific Antibodies ◽  
Leukocyte Antigen ◽  
Leukocyte Antigens ◽  
Antibody Reaction ◽  
Antigen Antibody

Abstract The interaction between leukocyte antigens and specific antibodies can cause lysis of the red cells of paroxysmal nocturnal hemoglobinuria (PNH) in vitro. It is suggested that the activation of complement ensuing from the antigen-antibody interaction is responsible for PNH cell lysis. The clinical implications of this finding are briefly outlined.

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