A relationship between serum basal tryptase (sBT) levels, anaphylactic reactions, and clonal mast cell diseases was shown recently in adults with venom allergy, but the relationship between sBT ...levels and IgE‐mediated food allergy and anaphylaxis is not known. In this study, children with food allergy (FA; n = 167) were analyzed in two groups according to the presence (FA+/A+; n = 79) or absence of anaphylaxis (FA+/A−; n = 88) and were compared with a control group (n = 113). Median sBT values in FA+/A+, FA+/A−, and control groups were 4.0 ng/ml (2.8–5.8), 3.6 (2.3–4.5), and 3.3 (2.4–4.4), respectively (P = 0.022). sBT measurements higher than the cutoff values of 5.7 and 14.5 were associated with 50% and 90% predicted probabilities, respectively, of moderate to severe anaphylaxis. Children with tree nuts/peanut allergies had significantly higher levels of sBT than children with milk and egg allergy (P = 0.022). Results suggest that sBT levels may predict moderate to severe anaphylaxis in children with food allergy, which may follow a particular pattern according to the food allergy phenotype.
Background
Indoleamine 2,3‐dioxygenase (IDO), which degrades tryptophan (Trp) to kynurenine (Kyn), has been demonstrated to contribute to modulation of allergic responses. However, the role of IDO in ...food allergy has not yet been elucidated.
Methods
Serum Trp and Kyn concentrations were analyzed by high‐pressure liquid chromatography. Expression of IDO gene was measured by real‐time PCR. The levels of interleukin (IL)‐4, IL‐10, and interferon (IFN)‐γ in cell culture supernatants were measured by ELISA.
Results
Kyn/Trp (IDO activity) was significantly lower in subjects with food allergy (n = 100) than in aged‐matched healthy controls (n = 112) (P = 0.004). Kyn/Trp was decreased from healthy through completely tolerant, partially tolerant, and reactive ones LN transformation (mean ± SEM) healthy: 3.9 ± 0.02 μM/mM; completely tolerant: 3.83 ± 0.04; partially tolerant: 3.8 ± 0.06; reactive: 3.7 ± 0.04 (P = 0.008). The frequency of genetic polymorphisms of IDO did not reveal a significant association with Trp, Kyn, and Kyn/Trp in healthy and food‐allergic cases. Culture of PBMC experiments yielded that IDO mRNA expression was not different between tolerant and reactive groups. IL‐4 synthesis when stimulated with casein increased significantly in subjects who are reactive and tolerant to foods (P = 0.042, P = 0.006, respectively). Increase in IL‐10 synthesis was observed only in children tolerant to milk, but not in reactive ones. IFN‐γ synthesis, when stimulated with IL‐2 and β‐lactoglobulin in cell culture, was significantly higher in subjects tolerant to milk than in the reactive ones (P = 0.005 and P = 0.029, respectively).
Conclusion
Our results imply the probability of involvement of IDO in development of tolerance process, and we presume that high IDO activity is associated with nonresponsiveness to food allergens despite allergen sensitization.
Summary
Background
Data‐driven methods such as hierarchical clustering (HC) and principal component analysis (PCA) have been used to identify asthma subtypes, with inconsistent results.
Objective
To ...develop a framework for the discovery of stable and clinically meaningful asthma subtypes.
Methods
We performed HC in a rich data set from 613 asthmatic children, using 45 clinical variables (Model 1), and after PCA dimensionality reduction (Model 2). Clinical experts then identified a set of asthma features/domains which informed clusters in the two analyses. In Model 3, we reclustered the data using these features to ascertain whether this improved the discovery process.
Results
Cluster stability was poor in Models 1 and 2. Clinical experts highlighted four asthma features/domains which differentiated the clusters in two models: age of onset, allergic sensitization, severity, and recent exacerbations. In Model 3 (HC using these four features), cluster stability improved substantially. The cluster assignment changed, providing more clinically interpretable results. In a 5‐cluster model, we labelled the clusters as: “Difficult asthma” (n = 132); “Early‐onset mild atopic” (n = 210); “Early‐onset mild non‐atopic: (n = 153); “Late‐onset” (n = 105); and “Exacerbation‐prone asthma” (n = 13). Multinomial regression demonstrated that lung function was significantly diminished among children with “Difficult asthma”; blood eosinophilia was a significant feature of “Difficult,” “Early‐onset mild atopic,” and “Late‐onset asthma.” Children with moderate‐to‐severe asthma were present in each cluster.
Conclusions and clinical relevance
An integrative approach of blending the data with clinical expert domain knowledge identified four features, which may be informative for ascertaining asthma endotypes. These findings suggest that variables which are key determinants of asthma presence, severity, or control may not be the most informative for determining asthma subtypes. Our results indicate that exacerbation‐prone asthma may be a separate asthma endotype and that severe asthma is not a single entity, but an extreme end of the spectrum of several different asthma endotypes.
Background
The importance of serum basal tryptase (sBT) levels on patients with venom allergy is highlighted in recent adulthood studies. The aim of this study was to evaluate the sBT levels of ...venom‐allergic children with varying severity of clinical reactions. We also aimed to document the association between sBT levels and severe systemic reactions (SR).
Methods
Serum basal tryptase levels were estimated by UniCAP (Pharmacia & Upjohn, Uppsala, Sweden). Children who suffered from large local reaction (LLR) or SR after insect stings were included along with healthy control subjects without a history of any local or SR after insect stings.
Results
A total of 128 children (55 with SR, 18 with LLR, and 55 age and sex‐matched control subjects) with a median age of 8.9 years (range 3.2–17.4) were enrolled. Severe SR was encountered in 24 (44%) patients with SRs. The median level of sBT in children with SRs (median, interquartile range) 4.2 μg/l (3.6–4.9) was significantly higher than in children with LLRs 3.1 μg/l (2.5–4.0) and healthy control subjects 2.9 μg/l (2.3–3.4) (P < 0.001). Logistic regression analysis revealed sBT ≥ 4.8 μg/l as a significant risk factor for severe SR (5.7 1.5–21.4; P = 0.01) in children with venom allergy.
Conclusions
Our results indicate that sBT levels are associated with a higher risk of severe SR in children with insect venom hypersensitivity. Determination of sBT levels may help clinicians to identify patients under risk of severe SRs and optimal and timely use of therapeutic interventions in children with venom allergy.
Aim
To evaluate the cytotoxicity and mineralization effects of iRoot BP in human dental pulp cells (hDPCs) and to compare them with those of white mineral trioxide aggregate (WMTA).
Methodology
hDPCs ...were exposed to prepared dilutions (1 : 1–1 : 10) of the test materials. Cell viability was evaluated using the XTT assay after incubation periods of 24, 48 or 72 h. The expression of mineralization‐related genes (bone morphogenic protein, osteonectin, bone sialoprotein, osteopontin, dentine sialophosphoprotein and collagen type 1) and heme oxygenase 1 was measured by quantitative real‐time polymerase chain reaction (qRT‐PCR) at 24 and 72 h. Statistical differences between test materials were analysed with the Mann–Whitney test.
Results
The 1 : 1 and 1 : 2 dilutions of iRoot BP were associated with higher cell viability after 24 h (P < 0.05). Only the 1 : 1 dilution of iRoot BP had higher cell viability after 48 h (P < 0.05), and there was no difference between iRoot BP and WMTA after 72 h (P > 0.05). Although somewhat variable, according to the gene expression results, iRoot BP had a mineralization potential similar to that of WMTA. WMTA revealed a higher heme oxygenase 1 (HO‐1) mRNA level than iRoot BP (P < 0.001).
Conclusions
iRoot BP and WMTA were biocompatible and facilitated odontoblastic differentiation of hDPCs.
To cite this article: Sackesen C, Birben E, Soyer OU, Sahiner UM, Yavuz TS, Civelek E, Karabulut E, Akdis M, Akdis CA, Kalayci O. The effect of CD14 C159T polymorphism on in vitro IgE synthesis and ...cytokine production by PBMC from children with asthma. Allergy 2011; 66: 48-57. ABSTRACT: Background: Even though the genotype at the promoter region of the CD14 molecule is known to affect the atopic phenotypes, the cellular and molecular basis of this association is largely unknown. Objective: To investigate the effect of lipopolysaccharide (LPS) on IgE production and cytokine profile by peripheral blood mononuclear cells (PBMC) obtained from asthmatic children with the TT and the CC genotypes at position −159 of the CD14 gene. Methods: Peripheral blood mononuclear cells from asthmatic children with alternative genotypes at CD14 C159T locus were stimulated with 2 and 200 ng/ml LPS in vitro. The IgE, IgG and, IgM response was determined by ELISA and Ig έ-germline, IgG, and IgM transcription by real-time PCR. A cluster of cytokines was measured by cytometric bead array. Results: Asthmatic children with the TT genotype but not those with the CC genotype responded with increased IgE synthesis and germline transcription to LPS stimulation. There were no genotype-related differences in IgG and IgM. TT but not the CC genotype was associated with significantly increased interleukin (IL)-4/IL-12 and IL-4/interferon-gamma (IFN-γ) ratios in the culture supernatant. There were no genotype-related differences in IL-1β, IL-7, IL-10, IL-13, IL-17A, granulocyte colony stimulating factor, granulocyte macrophage colony stimulating factor, monocyte chemotactic protein, and tumor necrosis factor alpha. Conclusion: Peripheral blood mononuclear cells from asthmatic children with the TT genotype at position −159 of the CD14 gene make more IgE than those with the CC genotype following LPS stimulation because of increased germline transcription and have an augmented Th2 cytokine profile.
Zusammenfassung
Hintergrund
Die Metallentfernung nach abgeschlossener Trichterbrustkorrektur fällt als elektiver Eingriff nicht selten zuerst den Kapazitätsengpässen der Operationsabteilung zum ...Opfer. Aufgrund dessen ist eine möglichst exakte Planung der zu erwartenden Schnitt-Naht-Zeit wünschenswert.
Ziel der Arbeit
Modellierung der Schnitt-Naht-Zeiten der Metallentfernung nach Nuss-Operation anhand der präspezifizierten unabhängigen Variablen Alter, Geschlecht, Anzahl der zu explantierenden Metallbügel sowie intraoperativ aufgetretener Komplikationen.
Material und Methoden
Wir schlossen retrospektiv alle Metallentfernungen nach Trichterbrustkorrektur zwischen Januar 2009 und Dezember 2020 in die Untersuchung ein. Diese wurden mittels linearer Regression modelliert und mittels Bootstrap intern validiert. Explorativ wurden zusätzlich die Erfahrung der Operateure, die Anzahl der Stabilisatoren sowie der Körpermasseindex und eine etwaige Revisionsoperation untersucht.
Ergebnisse
Wir schlossen 265 Patient:innen (14 % ♀) mit einem medianen Alter von 19 Jahren (Interquartilsabstand: 17–20) in die Untersuchung ein, wobei bei 81 % ein und bei 17 % zwei Metallbügel explantiert wurden. Das präspezifizierte Regressionsmodell war statistisch signifikant besser als das Nullmodell (Likelihood-Ratio 56; df = 5;
p
< 0,001) und hatte eine biaskorrigierte Modellgüte von
R
2
= 0,148. Das Patient:innenalter beeinflusste die Schnitt-Naht-Zeit um 2,1 min (95 %-Konfidenzintervall: 1,3–2,9;
p
< 0,001) pro Lebensjahr und jeder zu explantierende Metallbügel um 16 min (95 %-Konfidenzintervall: 10–22;
p
< 0,001).
Schlussfolgerung
Das Patient:innenalter wie auch der Anzahl der zu explantierenden Metallbügel können die Schnitt-Naht-Zeit beeinflussen und können in der Zeitplanung der Operation Berücksichtigung finden.
Background
Genetic variants in endotoxin signaling pathway are important in modulating the effect of environmental endotoxin on asthma and atopic phenotypes. Our objective was to determine the single ...nucleotide polymorphisms (SNPs) in the endotoxin signaling pathway that may influence in vitro IgE synthesis and to investigate the relationship between these variants and endotoxin exposure in relation to the development of asthma and atopy in a birth cohort.
Methods
Peripheral blood mononuclear cells from 45 children with asthma were stimulated with 2 and 200 ng/ml lipopolysaccharide in vitro and IgE was measured in the culture supernatants. Children were genotyped for 121 SNPs from 30 genes in the endotoxin signaling pathway. Variants with a dose–response IgE production in relation to lipopolysaccharide (LPS) were selected for replication in a population‐based birth cohort, in which we investigated the interaction between these SNPs and endotoxin exposure in relation to airway hyper‐responsiveness, wheeze, and atopic sensitization.
Results
Twenty‐one SNPs in nine genes (CD14, TLR4, IRF3, TRAF‐6, TIRAP, TRIF, IKK‐1, ST‐2, SOCS1) were found to modulate the effect of endotoxin on in vitro IgE synthesis, with six displaying high linkage disequilibrium. Of the remaining 15 SNPs, for seven we found significant relationships between genotype and endotoxin exposure in the genetic association study in relation to symptomatic airway hyper‐responsiveness (CD14‐rs2915863 and rs2569191, TRIF‐rs4807000), current wheeze (ST‐2‐rs17639215, IKK‐1‐rs2230804, and TRIF‐rs4807000), and atopy (CD14‐rs2915863 and rs2569192, TRAF‐6‐rs5030411, and IKK‐1‐rs2230804).
Conclusions
Variants in the endotoxin signaling pathway are important determinants of asthma and atopy. The genotype effect is a function of the environmental endotoxin exposure.
Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN) are diseases within the spectrum of severe cutaneous adverse reactions affecting skin and mucous membranes. Antiepileptic drugs ...(AEDs) are used in combination, leading to potential pharmacokinetic or pharmacodynamic interactions, causing more adverse effects than might occur when the AED is taken as monotherapy. Here, we report a rare case of SJS triggered by a combination of clobazam, lamotrigine and valproic acid in a 7-year-old boy. Because of inadequate seizure control, lorazepam was replaced with clobazam. Four weeks after the addition of clobazam, the patient developed SJS with a generalized rash, fever, with liver and kidney involvement, and eosinophilia one week after the initiation of treatment. All antiepileptic drugs were discontinued, and intravenous methylprednisolone, prophylactic systemic antibiotics, intravenous fluid supplement, antipyretic, special wound care, and supportive medical care for SJS were administered. He was discharged in a stable condition on the 18th day. Our case suggests that a drug-drug interaction between valproate, lamotrigine and clobazam contributed to the development of SJS. When the clobazam was added to valproic acid and lamotrigine co-medication, the lamotrigine dose should have been decreased.
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