Platelet-activating factor, PAF acetylhydrolase, and severe anaphylaxis.
BACKGROUND
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.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Vadas
Peter
P
Department of Medicine, Division of Allergy and Clinical Immunology, St. Michael's Hospital, Toronto, ON, Canada. vadasp@smh.toronto.on.ca .
Gold
Milton
M
Perelman
Boris
B
Liss
Gary M
GM
Lack
Gideon
G
Blyth
Thomas
T
Simons
F Estelle R
FE
Simons
Keith J
KJ
Cass
Dan
D
Yeung
Jupiter
J
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000097:blood*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000707:Anaphylaxis / Q000097:blood* / Q000401:mortality; D001249:Asthma / Q000097:blood / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004342:Drug Hypersensitivity / Q000097:blood; D004837:Epinephrine / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007273:Injections, Intramuscular; D007299:Insect Bites and Stings / Q000097:blood / Q000276:immunology; D008297:Male; D021183:Peanut Hypersensitivity / Q000097:blood*; D010972:Platelet Activating Factor / Q000032:analysis*; D011446:Prospective Studies; D012189:Retrospective Studies; D012307:Risk Factors; D012720:Severity of Illness Index
D015415:Biomarkers; D010972:Platelet Activating Factor; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D004837:Epinephrine