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Published on: December 15, 2014
Platelet-activating factor, PAF acetylhydrolase, and severe anaphylaxis.
Peter Vadas1, Milton Gold, Boris Perelman
1Department of Medicine, Division of Allergy and Clinical Immunology, St. Michael's Hospital, Toronto, ON, Canada. vadasp@smh.toronto.on.ca .
Platelet-activating factor (PAF) levels correlate with anaphylaxis severity in humans. Lower PAF acetylhydrolase activity, the enzyme inactivating PAF, is linked to severe and fatal anaphylaxis, suggesting its role in disease progression.
Area of Science:
- Immunology
- Allergy Research
- Biochemistry
Background:
- Platelet-activating factor (PAF) is a known mediator of anaphylaxis in animal models.
- Interventions targeting PAF have successfully prevented fatal anaphylaxis in animals.
- The specific roles of PAF and its inactivating enzyme, PAF acetylhydrolase, in human anaphylaxis remain largely uncharacterized.
Purpose of the Study:
- To investigate the association between serum Platelet-activating factor (PAF) levels and PAF acetylhydrolase activity in human patients experiencing anaphylaxis.
- To determine the correlation between PAF levels, PAF acetylhydrolase activity, and the severity of anaphylaxis, including fatal cases.
- To explore the potential role of PAF and PAF acetylhydrolase in the pathophysiology of human anaphylaxis.
Main Methods:
- Serum samples were collected from 41 patients diagnosed with anaphylaxis and 23 healthy control subjects.
- Measurements included serum PAF levels and PAF acetylhydrolase activity.
- Additional analysis compared PAF acetylhydrolase activity in patients with fatal peanut anaphylaxis against various control groups, including non-allergic individuals and those with mild or non-fatal allergic reactions.
Main Results:
- Patients with anaphylaxis exhibited significantly higher mean serum PAF levels compared to control groups, with levels correlating directly with anaphylaxis severity (P<0.001).
- A significant inverse correlation was observed between serum PAF levels and PAF acetylhydrolase activity (P<0.001).
- Lower PAF acetylhydrolase activity was increasingly prevalent with greater anaphylaxis severity and was significantly diminished in patients with fatal peanut anaphylaxis compared to all control groups (P<0.001).
Conclusions:
- Serum PAF levels are directly correlated with anaphylaxis severity in humans.
- Decreased PAF acetylhydrolase activity is inversely correlated with anaphylaxis severity and is notably low in fatal cases.
- Impaired inactivation of PAF by reduced PAF acetylhydrolase activity may be a contributing factor to the severity and lethality of human anaphylaxis.
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