Correspondence
Platelet-Activating Factor, PAF Acetylhydrolase, and Anaphylaxis
N Engl J Med 2008; 358:1515-1517April 3, 2008
- Article
To the Editor:
Vadas et al. (Jan. 3 issue)1 report platelet-activating factor (PAF) and PAF acetylhydrolase levels in patients with anaphylaxis.1 But why did the investigators not measure tryptase levels and correlate findings with PAF levels? Tryptase levels are the standard for understanding mast-cell activation in anaphylaxis and can be measured within 1 to 2 hours after its onset. This is an important consideration when a patient is in unstable condition2 and is important with PAF's short half-life. On the basis of the authors' suggestion that blocking PAF may alter clinical outcomes, it is important to correlate PAF levels temporally with clinical sequelae.
2 ReferencesJerrold H. Levy, M.D.
Emory University School of Medicine, Atlanta, GA 30322
jerrold.levy@emoryhealthcare. org 1
Vadas P ,Gold M ,Perelman B , et al. Platelet-activating factor, PAF acetylhydrolase, and severe anaphylaxis. N Engl J Med 2008;358:28-35
Full Text | Web of Science | Medline2
Schwartz LB . Diagnostic value of tryptase in anaphylaxis and mastocytosis. Immunol Allergy Clin North Am 2006;26:451-463
CrossRef | Web of Science | Medline
To the Editor:
Vadas et al. suggest that low levels of PAF acetylhydrolase may confer a predisposition to severe allergic reactions, and they observed rising levels of plasma PAF with increasing grades of anaphylaxis. We found no difference in the levels of either PAF acetylhydrolase protein or functional activity between 40 healthy controls and 63 persons in good health who were assessed several months after having had various grades of anaphylaxis1 in response to food, drug, and insect allergens (Table 1Table 1
Baseline PAF Acetylhydrolase Activity and Concentrations in Healthy Controls and Patients with Previous Anaphylaxis.).The ability of PAF acetylhydrolase to inactivate proinflammatory lipid mediators, including PAF, is reduced by oxidative damage and oxygen radicals.1,2 PAF can therefore inhibit its own degradation by PAF acetylhydrolase and may aggravate the symptoms of anaphylaxis. We suggest that rising levels of oxidative stress with worsening acute anaphylaxis3 may explain the inverse correlation between PAF and serum PAF acetylhydrolase activity. Consequently, measuring PAF acetylhydrolase activity after anaphylaxis, when patients are well, may provide little prognostic information.
3 ReferencesAmolak S. Bansal, D.M.
Epsom and St. Helier NHS Trust, Carshalton SM5 1AA, United Kingdom
amolak.bansal@epsom-sthelier. nhs. uk Ronnie Chee, M.R.C.Path.
Royal Free Hospital, London NW3 2QC, United KingdomNazira Sumar, Ph.D.
Epsom and St. Helier NHS Trust, Carshalton SM5 1AA, United Kingdom1
Brown SG . Clinical features and severity grading of anaphylaxis. J Allergy Clin Immunol 2004;114:371-376
CrossRef | Web of Science | Medline2
Ambrosio G ,Oriente A ,Napoli C , et al. Oxygen radicals inhibit human plasma acetylhydrolase, the enzyme that catabolizes platelet-activating factor. J Clin Invest 1994;93:2408-2416
CrossRef | Web of Science | Medline3
Levy JH . The human inflammatory response. J Cardiovasc Pharmacol 1996;27:Suppl 1:S31-S37
CrossRef | Web of Science | Medline
To the Editor:
Vadas et al. clearly demonstrate that serum PAF acetylhydrolase activity was inversely correlated with the severity of anaphylaxis in their study. There are some reports of high PAF levels and low PAF acetylhydrolase activity in other pathological conditions. Patients with neonatal necrotizing enterocolitis are reported to have high levels of PAF and decreased PAF acetylhydrolase activity.1 In addition, oxygenation in the immediate newborn period has been shown to up-regulate PAF acetylhydrolase activity and down-regulate PAF levels in an animal model,2 and hypoxia has been shown to increase stimulus-induced PAF production from human umbilical-vein endothelial cells.3 Therefore, low PAF acetylhydrolase activity in patients with fatal anaphylaxis might be caused by severe hypoxia followed by systemic necrosis. Further pathological studies showing how PAF acetylhydrolase activity is decreased in fatal anaphylaxis are expected to illuminate the role of low PAF acetylhydrolase in anaphylaxis.
3 ReferencesHiroshi Okamoto, M.D., Ph.D.
Naoyuki Kamatani, M.D., Ph.D.
Tokyo Women's Medical University, Tokyo 1620054, Japan
hokamoto@ior.twmu. ac. jp 1
Hsueh W ,Caplan MS ,Qu XW ,Tan XD ,De Plaen IG ,Gonzalez-Crussi F . Neonatal necrotizing enterocolitis: clinical considerations and pathogenetic concepts. Pediatr Dev Pathol 2003;6:6-23
CrossRef | Web of Science | Medline2
Ibe BO ,Sander FC ,Raj JU . Platelet activating factor acetylhydrolase activity in lamb lungs is up-regulated in the immediate newborn period. Mol Genet Metab 2000;69:46-55
CrossRef | Web of Science | Medline3
Caplan MS ,Adler L ,Kelly A ,Hsueh W . Hypoxia increases stimulus-induced PAF production and release from human umbilical vein endothelial cells. Biochim Biophys Acta 1992;1128:205-210
Web of Science | Medline
Author/Editor Response
Levy is correct in noting that tryptase levels are often a useful marker of mast-cell activation in anaphylaxis. We have performed comparative studies of tryptase, histamine, and PAF levels as a function of anaphylaxis severity in 41 patients who presented to an emergency department with acute allergic reactions. Space constraints did not permit inclusion of these data in our report. Although the proportion of elevated values increased across anaphylaxis grades for all three mediators, in grade 3 anaphylaxis, PAF, histamine, and tryptase levels were elevated in 100%, 70%, and 60% of patients, respectively.
Bansal et al. report similar PAF acetylhydrolase activity in patients with anaphylaxis and in controls. In the absence of detailed information on their methods, demographic characteristics of the anaphylaxis and control groups, case definitions of anaphylaxis, and analysis of PAF acetylhydrolase activity as a function of anaphylaxis severity, it is not possible to pinpoint the reasons for any discrepancies. We would nevertheless point out two important issues. If there was a preponderance of patients with grade 1 anaphylaxis, there would be little, if any, difference in PAF acetylhydrolase activity between patients and controls. More important, the mean PAF acetylhydrolase activity in the controls (9±5 nmol per minute per milliliter) was markedly below that reported in 16 published studies in which PAF acetylhydrolase activity ranged from 23.0±1.4 nmol per minute per milliliter to 55.6±11.2 nmol per minute per milliliter or more in healthy persons.
Okamoto and Kamatani make the valid point that other pathological conditions such as neonatal enterocolitis, and related sepsis, are characterized by high PAF levels and low PAF acetylhydrolase activity. The physiological similarities with severe anaphylaxis are striking. Both are characterized by decreased peripheral vascular resistance, increased pulmonary vascular resistance, increased vascular permeability, left ventricular dysfunction, and disseminated intravascular coagulation.1
1 ReferencesPeter Vadas, M.D., Ph.D.
Gary M. Liss, M.D.
University of Toronto, Toronto, ON M5B 1W8, Canada
vadasp@smh.toronto. on. ca F. Estelle R. Simons, M.D.
University of Manitoba, Winnipeg, MB R3A 1R9, Canada
