Platelet-Activating Factor, PAF Acetylhydrolase, and Severe Anaphylaxis

University of Toronto, Toronto, Ontario, Canada
New England Journal of Medicine (Impact Factor: 54.42). 01/2008; 358(1):28-35. DOI: 10.1056/NEJMoa070030
Source: PubMed

ABSTRACT Platelet-activating factor (PAF) is an important mediator of anaphylaxis in animals, and interventions that block PAF prevent fatal anaphylaxis. The roles of PAF and PAF acetylhydrolase, the enzyme that inactivates PAF, in anaphylaxis in humans have not been reported.
We measured serum PAF levels and PAF acetylhydrolase activity in 41 patients with anaphylaxis and in 23 control patients. Serum PAF acetylhydrolase activity was also measured in 9 patients with peanut allergy who had fatal anaphylaxis and compared with that in 26 nonallergic pediatric control patients, 49 nonallergic adult control patients, 63 children with mild peanut allergy, 24 patients with nonfatal anaphylaxis, 10 children who died of nonanaphylactic causes, 15 children with life-threatening asthma, and 19 children with non-life-threatening asthma.
Mean (+/-SD) serum PAF levels were significantly higher in patients with anaphylaxis (805+/-595 pg per milliliter) than in patients in the control groups (127+/-104 pg per milliliter, P<0.001 after log transformation) and were correlated with the severity of anaphylaxis. The proportion of subjects with elevated PAF levels increased from 4% in the control groups to 20% in the group with grade 1 anaphylaxis, 71% in the group with grade 2 anaphylaxis, and 100% in the group with grade 3 anaphylaxis (P<0.001). There was an inverse correlation between PAF levels and PAF acetylhydrolase activity (P<0.001). The proportion of patients with low PAF acetylhydrolase values increased with the severity of anaphylaxis (P<0.001 for all comparisons). Serum PAF acetylhydrolase activity was significantly lower in patients with fatal peanut anaphylaxis than in control patients (P values <0.001 for all comparisons).
Serum PAF levels were directly correlated and serum PAF acetylhydrolase activity was inversely correlated with the severity of anaphylaxis. PAF acetylhydrolase activity was significantly lower in patients with fatal anaphylactic reactions to peanuts than in patients in any of the control groups. Failure of PAF acetylhydrolase to inactivate PAF may contribute to the severity of anaphylaxis.

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    • "However, some studies have reported that the levels of PAF in serum correlates with the severity of the anaphylactic reaction while histamine or tryptase levels do not, and PAF acetylhydrolase activity, the enzyme responsible of PAF inactivation, inversely correlates with severity scores (Vadas et al., 2008), and thus PAF antagonists, alone or in combination with other drugs, may be a consideration as rescue therapy for acute anaphylaxis reactions. "
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    • "In early 70s a platelet-activating factor was first linked with allergy and IgE response [18]. This factor, so-called PAF, has been recently defined as an important mediator playing a pivotal role that correlates with the severity of anaphylaxis [19] [20]. In fact, the key treatment of anaphylaxis, epinephrine, has also been associated with human smooth muscle cells after stimulation with PAF [21]. "
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    • "Recently, basophils and probably macrophages , not mast cells, were shown to be the major players in IgG-but not IgE-mediated systemic anaphylaxis involving platelet-activating factor (PAF) (Tsujimura et al., 2008; Mukai et al., 2009). These mechanisms of anaphylaxis may also be relevant in humans, as serum PAF levels are correlated with the severity of anaphylaxis in patients (Vadas et al., 2008). Furthermore, a study of meta-analysis for patients with food allergy reported that although allergen-specifi c IgE in serum was highly relevant to allergic symptoms and useful diagnostic marker, a considerable part of patients did not always increase the specifi c IgE in serum (García et al., 2009). "
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