Platelet-Activating Factor, PAF Acetylhydrolase, and Severe Anaphylaxis

Abstract

Vadas P, Gold M, Perelman B, et al. N Engl J Med. 2008;358(1):28–35 PURPOSE OF THE STUDY. To characterize the roles of platelet-activating factor (PAF) and PAF acetylhydrolase, the enzyme that inactivates PAF, in humans. STUDY POPULATION. The population was a variety of pediatric and adult patients with different levels of allergic disease along with nonallergic controls. METHODS. Serum PAF levels and activity of PAF acetylhydrolase were measured 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 serum PAF levels were significantly higher in patients with anaphylaxis than in patients in the control groups 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. There was an inverse correlation between PAF levels and serum PAF acetylhydrolase activity. The proportion of patients with low PAF acetylhydrolase activity increased with the severity of anaphylaxis. Serum PAF acetylhydrolase activity was significantly lower in patients with fatal peanut anaphylaxis than in control patients. 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. REVIEWER COMMENTS. PAF is 1 of the proinflammatory mediators that are released systemically by the degranulation of mast cells and basophils. Although PAF is not the only mediator that plays a role in anaphylaxis, these results suggest that PAF is very important. Therefore, it may be useful to develop new pharmaceutical agents that block its actions. Additional research is also needed to determine if PAF and PAF acetylhydrolase measurements may be used as a screening tool to select patients at highest risk for fatal anaphylaxis.