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PubMed: 29929138

Title
Prothrombotic mechanisms in patients with congenital p.Cys89Tyr mutation in CD59.
Journal
Thrombosis research
Volume
168
Issue
None
Pages
67-77
Date
2018-08-01
Authors
Falach B | Hindi I | Karbian N | Mevorach D | Tabib A | Zelig O

Evidence 6b35bd831f
JSON

Both processes decrease the availability of NO, which normally maintains smooth muscle cell relaxation, inhibits platelet activation and aggregation, and has anti-inflammatory effects on the endothelium.

a(CHEBI:"nitric oxide") decreases bp(MESH:"Platelet Activation") View Subject | View Object

Appears in Networks:
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Cell Ontology (CL)
platelet
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Discussion

a(CHEBI:"nitric oxide") decreases bp(MESH:"Platelet Aggregation") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
platelet
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Discussion

a(CHEBI:"nitric oxide") decreases path(MESH:Inflammation) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
platelet
MeSH
Endothelium
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Discussion

rxn(reactants(a(CHEBI:arginine)), products(a(CHEBI:ornithine))) decreases a(CHEBI:"nitric oxide") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
platelet
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Discussion

Evidence 84db032648
JSON

Administration of heme in healthy volunteers caused thrombophlebitis, demonstrating that it can cause vascular inflammation followed by vascular obstruction [18].

a(CHEBI:heme) increases path(MESH:Inflammation) View Subject | View Object

Appears in Networks:
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Cell Ontology (CL)
erythrocyte
Cell Ontology (CL)
neutrophil
Cell Ontology (CL)
platelet
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Discussion

a(CHEBI:heme) increases path(HM:"vaso-occlusive crisis") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
Cell Ontology (CL)
neutrophil
Cell Ontology (CL)
platelet
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Discussion

a(CHEBI:heme) increases path(MESH:Thrombophlebitis) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
Cell Ontology (CL)
neutrophil
Cell Ontology (CL)
platelet
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Discussion

Evidence 33fd93983f
JSON

Endothelial injury may also be related to Free hemoglobin and its breakdown oxidative product heme, and MPs, which mediates direct proinflammatory, proliferative, and pro-oxidant effects on endothelial cells [22–24] both in PNH and congenital CD59 deficiency, but may be more pronounced in congenital CD59 deficiency and perhaps even more in the brain due to loss of CD59 in the endothelium of these patients.

a(CHEBI:heme) positiveCorrelation path(HM:"endothelial lesions") View Subject | View Object

Appears in Networks:
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Cell Ontology (CL)
platelet
MeSH
Endothelium
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Discussion

a(MESH:"Cell-Derived Microparticles") positiveCorrelation path(HM:"endothelial lesions") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
platelet
MeSH
Endothelium
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Discussion

p(HGNC:HBB) positiveCorrelation path(HM:"endothelial lesions") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
platelet
MeSH
Endothelium
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Discussion

path(HM:"endothelial lesions") positiveCorrelation p(HGNC:HBB) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
platelet
MeSH
Endothelium
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Discussion

path(HM:"endothelial lesions") positiveCorrelation a(CHEBI:heme) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
platelet
MeSH
Endothelium
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Discussion

path(HM:"endothelial lesions") positiveCorrelation a(MESH:"Cell-Derived Microparticles") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
platelet
MeSH
Endothelium
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Discussion

Evidence dea6c10930
JSON

In addition, lysed erythrocytes release arginase, which catalyzes the conversion of arginine, the substrate for NO synthesis, to ornithine.

a(HM:"Erythrocytes, lysed") increases a(MESH:Arginase) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
platelet
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Discussion

a(MESH:Arginase) positiveCorrelation rxn(reactants(a(CHEBI:arginine)), products(a(CHEBI:ornithine))) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
platelet
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Discussion

rxn(reactants(a(CHEBI:arginine)), products(a(CHEBI:ornithine))) positiveCorrelation a(MESH:Arginase) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
platelet
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Discussion

Evidence 7b470591be
JSON

Circulating MPs in PNH express the endothelial markers ICAM-1 (CD54), sVCAM-1, VWF, CD144, and CD105, indicating endothelial activation [24].

a(MESH:"Cell-Derived Microparticles") increases p(HGNC:ICAM1) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
platelet
MeSH
Endothelium
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Discussion

a(MESH:"Cell-Derived Microparticles") increases p(HGNC:VCAM1) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
platelet
MeSH
Endothelium
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Discussion

a(MESH:"Cell-Derived Microparticles") increases p(HGNC:VWF) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
platelet
MeSH
Endothelium
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Discussion

a(MESH:"Cell-Derived Microparticles") increases p(HGNC:CDH5) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
platelet
MeSH
Endothelium
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Discussion

a(MESH:"Cell-Derived Microparticles") increases p(HGNC:ENG) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
platelet
MeSH
Endothelium
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Discussion

Evidence 792a21966f
JSON

In this work, we were able to document a significant increase in RBCderived MPs, and a lesser increase in PMN- and platelet-derived MPs, in these patient s. This increase in MPs may lead to the thrombophilic state [15].

a(MESH:"Cell-Derived Microparticles") positiveCorrelation path(MESH:Thrombophilia) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
MeSH
Endothelium
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Discussion

path(MESH:Thrombophilia) positiveCorrelation a(MESH:"Cell-Derived Microparticles") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
MeSH
Endothelium
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Discussion

Evidence 909e3bd733
JSON

Surface accumulation of MAC may be at least partially responsible for the activated platelet phenotype seen in patients with primary Cys89Tyr CD59 mutation, as manifested both by increased CD62P expression and monocyte-platelet aggregates.

a(MESH:"Cell-Derived Microparticles") positiveCorrelation bp(MESH:"Platelet Activation") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
MeSH
Endothelium
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Discussion

bp(HM:"Monocyte-platelet aggregation") positiveCorrelation bp(MESH:"Platelet Activation") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
MeSH
Endothelium
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Discussion

bp(MESH:"Platelet Activation") positiveCorrelation p(HGNC:SELP) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
MeSH
Endothelium
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Discussion

bp(MESH:"Platelet Activation") positiveCorrelation bp(HM:"Monocyte-platelet aggregation") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
MeSH
Endothelium
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Discussion

bp(MESH:"Platelet Activation") positiveCorrelation a(MESH:"Cell-Derived Microparticles") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
MeSH
Endothelium
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Discussion

p(HGNC:SELP) positiveCorrelation bp(MESH:"Platelet Activation") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
MeSH
Endothelium
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Discussion

Evidence 89b1c5cbfd
JSON

Increased MAC deposition may lead to cell lysis and hemolysis, as is usually seen in RBCs but to a lesser extent in neutrophils and platelets (please see below).

a(MESH:"Complement Membrane Attack Complex") positiveCorrelation path(MESH:Hemolysis) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
Cell Ontology (CL)
neutrophil
Cell Ontology (CL)
platelet
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Results

path(MESH:Hemolysis) positiveCorrelation a(MESH:"Complement Membrane Attack Complex") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
Cell Ontology (CL)
neutrophil
Cell Ontology (CL)
platelet
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Results

Evidence 4ed4f50eb9
JSON

Following MAC deposition on RBCs, intravascular hemolysis that leads to increasing levels of free hemoglobin was seen.

a(MESH:"Complement Membrane Attack Complex") positiveCorrelation path(MESH:Hemolysis) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
Cell Ontology (CL)
neutrophil
Cell Ontology (CL)
platelet
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Results

p(HGNC:HBB) positiveCorrelation path(MESH:Hemolysis) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
Cell Ontology (CL)
neutrophil
Cell Ontology (CL)
platelet
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Results

path(MESH:Hemolysis) positiveCorrelation p(HGNC:HBB) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
Cell Ontology (CL)
neutrophil
Cell Ontology (CL)
platelet
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Results

path(MESH:Hemolysis) positiveCorrelation a(MESH:"Complement Membrane Attack Complex") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
Cell Ontology (CL)
neutrophil
Cell Ontology (CL)
platelet
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Results

Evidence 637c6fb4cf
JSON

As shown in Fig. 1, significantly increased MAC deposition is seen on RBCs (p < 0.0003), neutrophils (p < 0.009), and platelets (p < 0.0003), but not on monocytes (p=0.5, not shown).

a(MESH:"Complement Membrane Attack Complex") positiveCorrelation p(HGNC:CD59, var("p.Cys89Tyr")) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
Cell Ontology (CL)
neutrophil
Cell Ontology (CL)
platelet
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Results

p(HGNC:CD59, var("p.Cys89Tyr")) positiveCorrelation a(MESH:"Complement Membrane Attack Complex") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
Cell Ontology (CL)
neutrophil
Cell Ontology (CL)
platelet
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Results

p(HGNC:CD59, var("p.Cys89Tyr")) causesNoChange a(MESH:"Complement Membrane Attack Complex") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
monocyte
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Results

Evidence 46e6294c6b
JSON

However, in primary Cys89Tyr CD59 deficiency and not in PNH, the endothelial cells are exposed to MACmediated injury.

act(a(MESH:"Complement Membrane Attack Complex")) positiveCorrelation p(HGNC:CD59, var("p.Cys89Tyr")) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
platelet
MeSH
Endothelium
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Discussion

p(HGNC:CD59, var("p.Cys89Tyr")) positiveCorrelation act(a(MESH:"Complement Membrane Attack Complex")) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
platelet
MeSH
Endothelium
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Discussion

Evidence afd5b0ba35
JSON

The endothelium normally expresses high levels of CD59, which protects endothelial cells in healthy individuals and in PNH patients from MAC-mediated injury.

act(a(MESH:"Complement Membrane Attack Complex")) negativeCorrelation p(HGNC:CD59) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
platelet
MeSH
Endothelium
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Discussion

p(HGNC:CD59) negativeCorrelation act(a(MESH:"Complement Membrane Attack Complex")) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
platelet
MeSH
Endothelium
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Discussion

Evidence ac5bed6444
JSON

The average mean fluorescence (MF) for CD61 staining of was slightly reduced in patients with primary Cys89Tyr CD59 deficiency and PNH as compared to controls. However, the average MF for CD62P expression in the healthy individuals was 38.3 ± 3.1 compared to 48.5 ± 4.7 in patients with primary Cys89Tyr CD59 deficiency (p < 0.0085) and 54.0 ± 4.2 in patients with PNH (p < 0.0013), indicating a significantly more activated platelet phenotype in both the patients with PNH and those with primary Cys89Tyr CD59 deficiency.

bp(GO:"platelet activation") positiveCorrelation path(HP:"Paroxysmal nocturnal hemoglobinuria") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
Cell Ontology (CL)
neutrophil
Cell Ontology (CL)
platelet
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Results

p(HGNC:CD59, var("p.Cys89Tyr")) increases bp(GO:"platelet activation") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
Cell Ontology (CL)
neutrophil
Cell Ontology (CL)
platelet
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Results

path(HP:"Paroxysmal nocturnal hemoglobinuria") positiveCorrelation bp(GO:"platelet activation") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
Cell Ontology (CL)
neutrophil
Cell Ontology (CL)
platelet
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Results

Evidence e7bf6d1694
JSON

In contrast to platelet lysis, platelet activation is clearly seen, based on both the higher expression of CD62P (Fig. 3B) and increased coaggregation with white blood cells.

bp(HM:"Monocyte-platelet aggregation") positiveCorrelation bp(MESH:"Platelet Activation") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
MeSH
Endothelium
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Discussion

bp(MESH:"Platelet Activation") positiveCorrelation p(HGNC:SELP) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
MeSH
Endothelium
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Discussion

bp(MESH:"Platelet Activation") positiveCorrelation bp(HM:"Monocyte-platelet aggregation") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
MeSH
Endothelium
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Discussion

p(HGNC:SELP) positiveCorrelation bp(MESH:"Platelet Activation") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
MeSH
Endothelium
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Discussion

Evidence 3eed27ad1e
JSON

Although aggregation has not been investigated in PNH, we clearly show here that in primary Cys89Tyr CD59 mutation there is a significant increase in coaggregation with high numbers of activated platelets adhering to a single monocyte, and granulocytes to monocytes, that may lead to nonendothelial-bound arterial occlusion, among other effects [36].

bp(HM:"Monocyte-platelet aggregation") positiveCorrelation p(HGNC:CD59, var("p.Cys89Tyr")) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
MeSH
Endothelium
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Discussion

bp(HM:"Monocyte-platelet aggregation") positiveCorrelation path(HP:"Arterial occlusion") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
MeSH
Endothelium
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Discussion

p(HGNC:CD59, var("p.Cys89Tyr")) positiveCorrelation bp(HM:"Monocyte-platelet aggregation") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
MeSH
Endothelium
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Discussion

path(HP:"Arterial occlusion") positiveCorrelation bp(HM:"Monocyte-platelet aggregation") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
MeSH
Endothelium
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Discussion

Evidence 9428355388
JSON

Monocyte–platelet interactions are believed to be predominantly mediated by surface P-selectin/integrins and their receptors, and it was suggested that monocyte-platelet aggregates are a marker of platelet activation as well as a pathway for the regulation of monocyte and platelet function [17].

bp(HM:"Monocyte–platelet aggregation") positiveCorrelation p(HGNC:SELP) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
Cell Ontology (CL)
neutrophil
Cell Ontology (CL)
platelet
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Results

p(HGNC:SELP) positiveCorrelation bp(HM:"Monocyte–platelet aggregation") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
Cell Ontology (CL)
neutrophil
Cell Ontology (CL)
platelet
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Results

Evidence a5dd9ca034
JSON

MPs are small membrane-derived vesicles that are shed upon activation, inflammation, or cell death/damage.

bp(MESH:"Cell Death") increases a(MESH:"Cell-Derived Microparticles") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
platelet
MeSH
Endothelium
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Discussion

path(MESH:Inflammation) increases a(MESH:"Cell-Derived Microparticles") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
platelet
MeSH
Endothelium
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Discussion

Evidence 01b4a8f42f
JSON

This is a principal requirement for hemoglobin and hemin to induce adverse reactivity in tissues, including nitric oxide and oxidative reactions, release of free hemin, and molecular-signaling effects of hemin (reviewed by Schaer DJ et al.) [13] and Hill A et al. [14].

p(HGNC:HBB) increases a(HM:"oxidative reactions") View Subject | View Object

Appears in Networks:
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Cell Ontology (CL)
erythrocyte
Cell Ontology (CL)
neutrophil
Cell Ontology (CL)
platelet
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Results

Evidence 50eb60292d
JSON

High free hemoglobin was shown in patients with primary Cys89Tyr mutation in CD59 (Table 1) and it has been suggested in several ways that free hemoglobin may serve as a major mechanism for thrombophilia.

p(HGNC:HBB) positiveCorrelation path(MESH:Thrombophilia) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
Cell Ontology (CL)
neutrophil
Cell Ontology (CL)
platelet
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Results

p(HGNC:CD59, var("p.Cys89Tyr")) increases p(HGNC:HBB) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
Cell Ontology (CL)
neutrophil
Cell Ontology (CL)
platelet
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Results

path(MESH:Thrombophilia) positiveCorrelation p(HGNC:HBB) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
Cell Ontology (CL)
neutrophil
Cell Ontology (CL)
platelet
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Results

Evidence 303fe7d711
JSON

One mechanism that may contribute to enhanced platelet thrombus formation is inhibition of the metalloprotease ADAMTS13 by free hemoglobin [20].

p(HGNC:HBB) decreases p(HGNC:ADAMTS13) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
Cell Ontology (CL)
neutrophil
Cell Ontology (CL)
platelet
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Discussion

p(HGNC:ADAMTS13) decreases a(HM:Thrombus) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
platelet
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Discussion

Evidence e9dbaed16c
JSON

Injured endothelium may provide tissue factors and additional prothrombotic factors [21] that are not a prothrombotic mechanism in PNH.

p(HGNC:F3) positiveCorrelation path(HM:"endothelial lesions") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
platelet
MeSH
Endothelium
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Discussion

path(HM:"endothelial lesions") positiveCorrelation p(HGNC:F3) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
platelet
MeSH
Endothelium
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Discussion

Evidence 01c221b6e7
JSON

free hemoglobin is rapidly cleared from the circulation by several scavenging mechanisms; however, we found that the plasma-free hemoglobin was high and haptoglobin levels were low in the patients examined (Table 1).

p(HGNC:HP) decreases p(HGNC:HBB) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
Cell Ontology (CL)
neutrophil
Cell Ontology (CL)
platelet
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Results

Evidence 7388e6a220
JSON

Interestingly, we have recently reported an association with venous thrombosis for lack of CD55 [45], so PNH patients lacking both CD55 and CD59 may suffer from both venous and arterial thrombosis.

p(HGNC:CD55) negativeCorrelation path(HP:"Arterial thrombosis") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
MeSH
Coronary Vessels
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Discussion

p(HGNC:CD55) negativeCorrelation path(HP:"Venous thrombosis") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
MeSH
Coronary Vessels
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Discussion

p(HGNC:CD59) negativeCorrelation path(HP:"Arterial thrombosis") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
MeSH
Coronary Vessels
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Discussion

p(HGNC:CD59) negativeCorrelation path(HP:"Venous thrombosis") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
MeSH
Coronary Vessels
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Discussion

path(HP:"Arterial thrombosis") negativeCorrelation p(HGNC:CD59) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
MeSH
Coronary Vessels
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Discussion

path(HP:"Arterial thrombosis") negativeCorrelation p(HGNC:CD55) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
MeSH
Coronary Vessels
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Discussion

path(HP:"Venous thrombosis") negativeCorrelation p(HGNC:CD55) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
MeSH
Coronary Vessels
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Discussion

path(HP:"Venous thrombosis") negativeCorrelation p(HGNC:CD59) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
MeSH
Coronary Vessels
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Discussion

Evidence caafc31888
JSON

PIGA encodes a GPI biosynthesis protein, phosphatidylinositol N-acetylglucosaminyltransferase subunit A [5, 6], and erythrocytes deficient in GPI-anchored membrane proteins, including CD59, undergo complement-mediated hemolysis.

p(HGNC:CD59) negativeCorrelation path(MESH:Hemolysis) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Introduction

path(MESH:Hemolysis) negativeCorrelation p(HGNC:CD59) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Introduction

Evidence 484a6a21b3
JSON

CD59 deficiency is a common finding in adult patients with PNH, which is characterized by clonal expansion of hematopoietic stem cells that have acquired a mutation in the PIGA gene (phosphatidylinositol glycan anchor biosynthesis, class A).

p(HGNC:CD59) negativeCorrelation path(HP:"Paroxysmal nocturnal hemoglobinuria") View Subject | View Object

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MeSH
Hemoglobinuria, Paroxysmal
Text Location
Introduction

path(HP:"Paroxysmal nocturnal hemoglobinuria") negativeCorrelation p(HGNC:CD59) View Subject | View Object

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MeSH
Hemoglobinuria, Paroxysmal
Text Location
Introduction

Evidence 2a80e82b01
JSON

Nonfunctioning CD59 is a major risk factor for stroke and hypercoagulability.

p(HGNC:CD59, var("p.Cys89Tyr")) increases path(MESH:Stroke) View Subject | View Object

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Abstract

p(HGNC:CD59, var("p.Cys89Tyr")) increases path(HP:Hypercoagulability) View Subject | View Object

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Abstract

Evidence b9be1b57d8
JSON

More recently, we have described two infants carrying the mutation who manifested with recurrent strokes [8], establishing the concept that primary Cys89Tyr mutation in CD59 leads to a thrombophilic state.

p(HGNC:CD59, var("p.Cys89Tyr")) positiveCorrelation path(MESH:Stroke) View Subject | View Object

Appears in Networks:
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MeSH
Hemoglobinuria, Paroxysmal
Text Location
Introduction

p(HGNC:CD59, var("p.Cys89Tyr")) positiveCorrelation path(MESH:Thrombosis) View Subject | View Object

Appears in Networks:
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MeSH
Hemoglobinuria, Paroxysmal
Text Location
Introduction

path(MESH:Stroke) positiveCorrelation p(HGNC:CD59, var("p.Cys89Tyr")) View Subject | View Object

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MeSH
Hemoglobinuria, Paroxysmal
Text Location
Introduction

path(MESH:Thrombosis) positiveCorrelation p(HGNC:CD59, var("p.Cys89Tyr")) View Subject | View Object

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MeSH
Hemoglobinuria, Paroxysmal
Text Location
Introduction

Evidence b5ec689321
JSON

We recently encountered patients with recurrent strokes leading to premature death in 2/7 young children with primary Cys89Tyr CD59 deficiency [8].

p(HGNC:CD59, var("p.Cys89Tyr")) increases path(MESH:Stroke) View Subject | View Object

Appears in Networks:
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Cell Ontology (CL)
erythrocyte
MeSH
Coronary Vessels
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Discussion

Evidence e483e183b3
JSON

The Cys89Tyr mutation in CD59 was initially described with manifestation in infancy by chronic hemolysis and relapsing peripheral demyelinating disease resembling recurrent Guillain- Barre syndrome (GBS) or chronic inflammatory demyelinating polyneuropathy (CIDP).

p(HGNC:CD59, var("p.Cys89Tyr")) positiveCorrelation path(MESH:Hemolysis) View Subject | View Object

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MeSH
Hemoglobinuria, Paroxysmal
Text Location
Introduction

p(HGNC:CD59, var("p.Cys89Tyr")) positiveCorrelation path(MESH:"Guillain-Barre Syndrome") View Subject | View Object

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MeSH
Hemoglobinuria, Paroxysmal
Text Location
Introduction

p(HGNC:CD59, var("p.Cys89Tyr")) positiveCorrelation path(MESH:"Polyradiculoneuropathy, Chronic Inflammatory Demyelinating") View Subject | View Object

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MeSH
Hemoglobinuria, Paroxysmal
Text Location
Introduction

path(MESH:"Guillain-Barre Syndrome") positiveCorrelation p(HGNC:CD59, var("p.Cys89Tyr")) View Subject | View Object

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MeSH
Hemoglobinuria, Paroxysmal
Text Location
Introduction

path(MESH:"Polyradiculoneuropathy, Chronic Inflammatory Demyelinating") positiveCorrelation p(HGNC:CD59, var("p.Cys89Tyr")) View Subject | View Object

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MeSH
Hemoglobinuria, Paroxysmal
Text Location
Introduction

path(MESH:Hemolysis) positiveCorrelation p(HGNC:CD59, var("p.Cys89Tyr")) View Subject | View Object

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MeSH
Hemoglobinuria, Paroxysmal
Text Location
Introduction

Evidence 016c7dfdf8
JSON

In summary, thrombosis is an extremely important prognostic factor both in PNH and in primary Cys89Tyr nonfunctioning CD59.

p(HGNC:CD59, var("p.Cys89Tyr")) positiveCorrelation path(MESH:Thrombosis) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
MeSH
Coronary Vessels
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Discussion

path(HP:"Paroxysmal nocturnal hemoglobinuria") positiveCorrelation path(MESH:Thrombosis) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
MeSH
Coronary Vessels
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Discussion

path(MESH:Thrombosis) positiveCorrelation path(HP:"Paroxysmal nocturnal hemoglobinuria") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
MeSH
Coronary Vessels
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Discussion

path(MESH:Thrombosis) positiveCorrelation p(HGNC:CD59, var("p.Cys89Tyr")) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
MeSH
Coronary Vessels
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Discussion

Evidence 0ca6f2dfff
JSON

We have assessed the presence of MPs in four patients with primary Cys89Tyr mutation in CD59 and two PNH patients, as well as in four healthy donors.

p(HGNC:CD59, var("p.Cys89Tyr")) increases a(MESH:"Cell-Derived Microparticles") View Subject | View Object

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Annotations
Cell Ontology (CL)
erythrocyte
Cell Ontology (CL)
neutrophil
Cell Ontology (CL)
platelet
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Results

path(HP:"Paroxysmal nocturnal hemoglobinuria") increases a(MESH:"Cell-Derived Microparticles") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
Cell Ontology (CL)
neutrophil
Cell Ontology (CL)
platelet
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Results

Evidence c58ff040f9
JSON

In summary, patients with primary Cys89Tyr mutation in CD59 showed about 9–10-fold increase in the number of MPs compared to controls and slightly but significantly increased numbers when com pared to PNH patients. The origin of MPs was primarily RBCs and to a much lesser extent platelets and neutrophils.

p(HGNC:CD59, var("p.Cys89Tyr")) increases a(MESH:"Cell-Derived Microparticles") View Subject | View Object

Appears in Networks:
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Cell Ontology (CL)
erythrocyte
Cell Ontology (CL)
neutrophil
Cell Ontology (CL)
platelet
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Results

path(HP:"Paroxysmal nocturnal hemoglobinuria") increases a(MESH:"Cell-Derived Microparticles") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
Cell Ontology (CL)
neutrophil
Cell Ontology (CL)
platelet
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Results

Evidence 6c146f7f2b
JSON

It is thus plausible to suggest that the increased monocyte-platelet interaction in patients with primary Cys89Tyr mutation in CD59 is related to an activated platelet phenotype.

p(HGNC:CD59, var("p.Cys89Tyr")) increases bp(GO:"platelet activation") View Subject | View Object

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Cell Ontology (CL)
erythrocyte
Cell Ontology (CL)
neutrophil
Cell Ontology (CL)
platelet
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Results

Evidence 2700e655ee
JSON

Interaction between monocytes and platelets was suggested to be via p selection [17], which was shown here to be much higher in patients with primary Cys89Tyr mutation in CD59.

p(HGNC:CD59, var("p.Cys89Tyr")) increases p(HGNC:SELP) View Subject | View Object

Appears in Networks:
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Cell Ontology (CL)
erythrocyte
Cell Ontology (CL)
neutrophil
Cell Ontology (CL)
platelet
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Results

Evidence d2b0d6535b
JSON

Ziakas et al. [38] described 38 reports of arterial thrombosis, mainly in the central nervous system or coronary arteries in PNH patients.

path(HP:"Arterial thrombosis") positiveCorrelation path(HP:"Paroxysmal nocturnal hemoglobinuria") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
MeSH
Coronary Vessels
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Discussion

path(HP:"Paroxysmal nocturnal hemoglobinuria") positiveCorrelation path(HP:"Arterial thrombosis") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
MeSH
Coronary Vessels
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Discussion

Evidence 3b6f947689
JSON

Thrombosis is the prognostic factor with the greatest effect on survival in paroxysmal nocturnal hemoglobinuria (PNH) patients [1, 2].

path(HP:"Paroxysmal nocturnal hemoglobinuria") positiveCorrelation path(MESH:Thrombosis) View Subject | View Object

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Introduction

path(MESH:Thrombosis) positiveCorrelation path(HP:"Paroxysmal nocturnal hemoglobinuria") View Subject | View Object

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Text Location
Introduction

Evidence 420ad72245
JSON

Data from several retrospective studies in the preeculizumab era showed that the cause of death was related to thrombosis in 22.2–37.2% of PNH patients.

path(MESH:Death) positiveCorrelation path(MESH:Thrombosis) View Subject | View Object

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MeSH
Hemoglobinuria, Paroxysmal
Text Location
Introduction

path(MESH:Thrombosis) positiveCorrelation path(MESH:Death) View Subject | View Object

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MeSH
Hemoglobinuria, Paroxysmal
Text Location
Introduction

Evidence 0ff8a0c84b
JSON

Excessive intravascular hemolysis saturates scavenger mechanisms, resulting in free hemoglobin in plasma that irreversibly reacts with nitric oxide (NO) to form nitrate and methemoglobin.

path(MESH:Hemolysis) increases p(HGNC:HBB) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
platelet
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Discussion

Evidence a8c193b10c
JSON

Intravascular hemolysis is one thrombophilic mechanisms in PNH (reviewed by Hill et al. [14]).

path(MESH:Hemolysis) positiveCorrelation path(MESH:Thrombophilia) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
Cell Ontology (CL)
neutrophil
Cell Ontology (CL)
platelet
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Discussion

path(MESH:Thrombophilia) positiveCorrelation path(MESH:Hemolysis) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
Cell Ontology (CL)
neutrophil
Cell Ontology (CL)
platelet
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Discussion

About

BEL Commons is developed and maintained in an academic capacity by Charles Tapley Hoyt and Daniel Domingo-Fernández at the Fraunhofer SCAI Department of Bioinformatics with support from the IMI project, AETIONOMY. It is built on top of PyBEL, an open source project. Please feel free to contact us here to give us feedback or report any issues. Also, see our Publishing Notes and Data Protection information.

If you find BEL Commons useful in your work, please consider citing: Hoyt, C. T., Domingo-Fernández, D., & Hofmann-Apitius, M. (2018). BEL Commons: an environment for exploration and analysis of networks encoded in Biological Expression Language. Database, 2018(3), 1–11.