Serum platelet activating factor levels predicts refractoriness to antihistamine treatment in chronic spontaneous urticaria

Abstract

This work was supported by a grant from the National Research Foundation of Korea (NRF) funded by the Korea government (MSIP) (NRF-2018R1A2B6006199) and a research grant from Ahn-Gook Pharmaceutical Co, Ltd, Seoul, Republic of Korea. Platelet activating factor (PAF) is one of the most potent phospholipid released from platelets as well as various inflammatory cells. PAF has been known to play a role in the regulation of immune responses and allergic inflammation. This study was aimed to compare circulating levels of PAF and PAF-acetylhydrolase (AH) which can catabolize PAF in patients with chronic spontaneous urticarial (CSU) and healthy controls (NC) and to investigate relationships of their levels and urticaria severity and therapeutic response. Serum PAF and PAF-AH levels were measured by ELISA in 283 CSU patients and 111 age- and sex-matched 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. Serum PAF levels were higher in CSU patients than in NCs (median 4368.9 [17.0–14768.3] vs. 3256.4 [27.1–13886.7] pg/ml, p = 0.015), while serum PAF-AH levels were lower in CSU patients (105.6 [2.6–296.4] vs. 125.7 [2.0–291.1] ng/ml, p = 0.001). H1RA non-responders had higher levels of PAF (3804.5 [17.0–11716.3] vs. 5426.3 [53.1–14768.3], p < 0.001) in their sera. A generalized linear model revealed that a higher UAS7 score (odds ratio 1.023) and a PAF level ≥ 5000 pg/ml (1.409) were significant predictors of a poor response to H1RA treatment. CSU patients, particularly those with H1RA refractoriness, showed significant increases in serum PAF levels and decreases in PAF-AH as compared with NCs. Therapies modulating PAF and PAF-AH levels could be effective in patients with CSU refractory to antihistamines.