Abstract
BackgroundPlatelet activating factor (PAF) is an endogenous, active phospholipid released from inflammatory cells, platelets, and endothelial cells, and is involved in the regulation of immune responses. Degradation of PAF by PAF acetylhydrolase (PAF-AH) has been shown to be associated with anaphylaxis, asthma, and peanut allergy. The purpose of this study was to investigate relationships among clinical parameters, including urticaria severity and treatment responsiveness, and PAF and PAF-AH levels in sera from patients with chronic spontaneous urticaria (CSU).MethodsSerum PAF and PAF-AH levels were measured by enzyme-linked immunosorbent assay in 283 CSU patients and 111 age- and sex-matched, healthy normal controls (NCs). Urticaria severity was evaluated by urticaria activity score over 7 days (UAS7). Within 3 months after measuring PAF levels, patients whose urticaria was not controlled by antihistamine treatment were classified as histamine receptor 1 antagonist (H1RA) non-responders.ResultsSerum PAF levels were significantly higher in CSU patients than in NCs (median 4368.9 vs. 3256.4 pg/ml, p = 0.015), while serum PAF-AH levels were significantly lower in CSU patients (105.6 vs. 125.7 ng/ml, p = 0.001). H1RA non-responders had higher levels of PAF in their sera than H1RA responders. A generalized linear model revealed that a higher UAS7 score (odds ratio 1.023, p = 0.024) and a PAF level ≥ 5000 pg/ml (1.409, p < 0.001) were significant predictors of a poor response to H1RA treatment.ConclusionsCompared with NCs, CSU patients, particularly those with H1RA refractoriness, showed significant increases in serum PAF levels and decreases in PAF-AH. Therapies modulating PAF and PAF-AH levels could be effective in patients with CSU refractory to antihistamines.
Highlights
Platelet activating factor (PAF) is an endogenous, active phospholipid released from inflammatory cells, platelets, and endothelial cells, and is involved in the regulation of immune responses
CSU chronic spontaneous urticaria, NC healthy normal control, Body mass index (BMI) body mass index, not assessible (NA) not assessable, UAS7 urticaria activity score over 7 days, Autologous serum skin test (ASST) autologous serum skin test, Anti-nuclear antibody (ANA) anti-nuclear antibody, ECP eosinophilic cationic protein, LDL low density lipoprotein, high density lipopro‐ tein (HDL) high density lipoprotein and non-responders, nor were there any significant differences in BMI (23.4 ± 4.1 vs. 23.6 ± 3.6, p = 0.577)
The present study demonstrates that PAF levels are increased and that PAF acetylhydrolase (PAF-AH) levels are decreased in the sera from CSU patients, compared with those in healthy controls
Summary
Platelet activating factor (PAF) is an endogenous, active phospholipid released from inflammatory cells, platelets, and endothelial cells, and is involved in the regulation of immune responses. The purpose of this study was to investigate relationships among clinical parameters, including urticaria severity and treatment responsiveness, and PAF and PAF-AH levels in sera from patients with chronic spontaneous urticaria (CSU). CU is classified into inducible urticaria (induced by specific physical triggers) and Ulambayar et al Clin Transl Allergy (2019) 9:33 chronic spontaneous urticaria (CSU) [6]. Plasma extravasation, and inflammatory cell migration to urticarial lesions, mast cells and basophils release various inflammatory mediators, including histamine, protease, cytokines, chemotactic factors, arachidonic acid metabolites, neuropeptides, and PAF [6]. Except for histamine, the roles of inflammatory mediators in the pathogenesis of CSU have yet to be thoroughly investigated
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