ABSTRACT
Background: There is currently little research into factors predicting the results of an initial diagnostic oral food challenge (OFC) test for food protein-induced enterocolitis syndrome (FPIES). Objective: The present study aimed to identify predictors of the diagnosis of hen's egg yolk-induced FPIES (HEY-FPIES). Methods: The present monocentric study was performed at Tokyo Metropolitan Children's Medical Center and included patients who underwent hen's egg yolk OFC (HEY-OFC) between March 2018 and March 2023 to assess for HEY-FPIES. The baseline characteristics of the groups and HEY-OFC positivity or negativity were then compared. Univariate analysis was conducted by using the Mann-Whitney U test or Fisher exact test. Receiver operator characteristic analysis was used to create probability curves. Results: In total, 35 patients were analyzed; of these, 17 were HEY-OFC-positive. No significant difference was observed between the HEY-OFC-positive and HEY-OFC-negative groups in terms of background factors except for the HEY-LST value, which was significantly higher in the HEY-LST group (P = .027). Receiver operator characteristic analysis demonstrated that the area under the curve for HEY-OFC positivity using the HEY-LST value was 0.719 (95% CI = 0.541-0.897). The statistically optimal cutoff value for the HEY-LST was 610%, which had a clinical sensitivity and specificity of 64.7% and 83.3%, respectively. Conclusions: The present study demonstrated that the HEY-LST may be a useful predictor of the result of an initial OFC for HEY-FPIES.
ABSTRACT
Leak K(+) conductance generated by TASK1/3 channels is crucial for neuronal excitability. However, endogenous modulators activating TASK channels in neurons remained unknown. We previously reported that in the presumed cholinergic neurons of the basal forebrain (BF), activation of NO-cGMP-PKG (protein kinase G) pathway enhanced the TASK1-like leak K(+) current (I-K(leak)). As 8-Br-cGMP enhanced the I-K(leak) mainly at pH 7.3 as if changing the I-K(leak) from TASK1-like to TASK3-like current, such an enhancement of the I-K(leak) would result either from an enhancement of hidden TASK3 component or from an acidic shift in the pH sensitivity profile of TASK1 component. In view of the report that protonation of TASK channel decreases its open probability, the present study was designed to examine whether the activation of PKG increases the conductance of TASK1 channels by reducing their binding affinity for H(+), i.e., by increasing K(d) for protonation, or not. We here demonstrate that PKG activation and inhibition respectively upregulate and downregulate TASK1 channels heterologously expressed in PKG-loaded HEK293 cells at physiological pH, by causing shifts in the K(d) in the acidic and basic directions, respectively. Such PKG modulations of TASK1 channels were largely abolished by mutating pH sensor H98. In the BF neurons that were identified to express ChAT and TASK1 channels, similar dynamic modulations of TASK1-like pH sensitivity of I-K(leak) were caused by PKG. It is strongly suggested that PKG activation and inhibition dynamically modulate TASK1 currents at physiological pH by bidirectionally changing K(d) values for protonation of the extracellular pH sensors of TASK1 channels in cholinergic BF neurons.
