Inter-individual variability of plasma PAF-acetylhydrolase activity in ARDS patients and PAFAH genotype

Background: Platelet activating factor (PAF), a pro-inflammatory phospholipid, stimulates cytokine secretion from polymorphonuclear leukocytes expressing the transmembrane G-protein coupled PAF receptor. Elevated PAF levels are associated with acute respiratory distress syndrome (ARDS) and sepsis severity. The pro-inflammatory effects of PAF are terminated by PAF acetylhydrolase (PAF-AH). Objective: We sought to determine whether allelic variants in the human PAFAH gene (Arg92His, Ile198Thr, and Ala379Val) contribute to variability in PAF-AH activity in patient plasma obtained within 72 h of ARDS diagnosis. Results: Plasma PAF-AH activity (mean +/- SD) was higher in patients homozygous for the Arg92 allele compared to His92 allele carriers (2 center dot 21 +/- 0 center dot 77 vs. 1 center dot 64 +/- 0 center dot 68 U/min; P < 0 center dot 01; n = 31 and 21 respectively). Baseline plasma PAF-AH activity was higher among day 7 survivors vs. day 7 non-survivors (2 center dot 05 +/- 0 center dot 75 vs. 1 center dot 27 +/- 0 center dot 63, P = 0 center dot 05). Conclusion: These data demonstrate an association between PAF-AH allelic variation, plasma activity, and outcome in ARDS.