Abstract
Background
Specific IgE (sIgE) against the peanut component Arachis hypogaea (Ara h) 2 has been shown to be the most important allergen to discriminate between peanut allergy and peanut ...tolerance. Several studies determined sIgE cut off values for Ara h 2, determined by singleplex measurements. However, cut off values for Ara h 2 from multiplex arrays are less well defined. The aim of this study was to evaluate the correlation between Ara h 2 sIgE determined by singleplex versus multiplex measurements and to assess the diagnostic value of the different peanut components included in Immuno Solid-phase Allergen Chip (ISAC) multiplex analysis in children with a suspected peanut allergy.
Methods
In this retrospective study we analyzed Ara h 2 sIgE values with singleplex Fluorescence Enzyme Immunoassay (FEIA, ImmunoCap) and multiplex microarray (ISAC) measurements in 117 children with a suspected peanut allergy. Also, other peanut components measured by ISAC were analyzed. Double blinded placebo controlled oral food challenges were used as golden standard.
Results
Among all studied peanut components FEIA Ara h 2 sIgE showed the highest area under the curve (AUC, 0.922), followed by ISAC Ara h 6 and Ara h 2 sIgE with AUCs of respectively 0.906 and 0.902. Best cut off values to diagnose peanut allergy were 4.40 kU/l for FEIA Ara h 2 sIgE and, 7.43 ISU and 8.13 ISU for respectively Ara h 2 and Ara h 6 sIgE in ISAC microarray. Ara h 2 sIgE determined in FEIA and ISAC showed a good correlation (r = 0.88; p < 0.01).
Conclusion
Ara h 6 and Ara h 2 sIgE in multiplex ISAC are both good predictors of clinical peanut allergy in Dutch children, and their performance is comparable to the use of Ara h 2 in singleplex FEIA. The simultaneous measurement of different peanut components using ISAC is an advantage and clinically useful to detect peanut allergic children that are Ara h 2 negative but sensitized to other peanut proteins such as Ara h 6.
Despite the critical role of soluble IgE in the pathology of IgE‐mediated allergic disease, little is known about abnormalities in the memory B cells and plasma cells that produce IgE in allergic ...patients. We here applied a flow cytometric approach to cross‐sectionally study blood IgE+ memory B cells and plasmablasts in 149 children with atopic dermatitis, food allergy, and/or asthma and correlated these to helper T(h)2 cells and eosinophils. Children with allergic disease had increased numbers of IgE+CD27‐ and IgE+CD27+ memory B cells and IgE+ plasmablasts, as well as increased numbers of eosinophils and Th2 cells. IgE+ plasmablast numbers correlated positively with Th2 cell numbers. These findings open new possibilities for diagnosis and monitoring of treatment in patients with allergic diseases.
Several mixed microbial communities have been reported to show robust bioelectrocatalysis of oxygen reduction over time at applicable operation conditions. However, clarification of electron transfer ...mechanism(s) and identification of essential micro-organisms have not been realised. Therefore, the objective of this study was to shape oxygen reducing biocathodes with different microbial communities by means of surface modification using the electrochemical reduction of two different diazonium salts in order to discuss the relation of microbial composition and performance. The resulting oxygen reducing mixed culture biocathodes had complex bacterial biofilms variable in size and shape as observed by confocal and electron microscopy. Sequence analysis of ribosomal 16S rDNA revealed a putative correlation between the abundance of certain microbiota and biocathode performance. The best performing biocathode developed on the unmodified graphite electrode and reached a high current density for oxygen reducing biocathodes at neutral pH (0.9A/m2). This correlated with the highest domination (60.7%) of a monophyletic group of unclassified γ-Proteobacteria. These results corroborate earlier reports by other groups, however, higher current densities and higher presence of these unclassified bacteria were observed in this work. Therefore, members of this group are likely key-players for highly performing oxygen reducing biocathodes.
•Best oxygen reducing biocathode reached high current density (0.9A/m2).•Sequencing revealed relationship between microbiota and biocathode performance.•Domination of so far unclassified γ-Proteobacteria in best biocathode (60.7%)•This bacterial group was a key-player for high performing oxygen reducing biocathode.
Here, we summarise the current clinical knowledge on Ara h 6 sensitisation and clinical relevance of this sensitisation pattern using five illustrative clinical cases. The literature search yielded a ...total of 166 papers, and an additional relevant article was found by ‘snowballing’. A total of ten articles were considered relevant for this review. Most studies included patients with a sensitisation to Ara h 6 and cosensitisation to Ara h 2. Only three studies showed patients with a mono-sensitisation to Ara h 6. This illustrates that Ara h 6 mono-sensitisation has been neglected in literature. We present a case series of five children with sensitisation to peanut component Ara h 6. Only one of these five patients showed Ara h 8 cosensitivity. Three out of the five children had a positive double-blind placebo-controlled food challenge (DBPCFC), with moderate to strong reactions.
Conclusion
: A mono-sensitisation to peanut component Ara h 6 is uncommon but can cause severe allergic reactions. Therefore, the determination of sIgE to Ara h 6 is warranted in patients with a suspected peanut allergy, especially in the absence of sensitisation to Ara h 1, 2, 3 and 9.
What is known
:
•
Peanut allergy is common and can cause severe allergic reactions
.
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The diagnostics of peanut allergy has recently improved with the use of component resolved diagnosis
What is new
:
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A mono
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sensitisation to peanut component Ara h 6 is uncommon
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but can cause severe allergic reactions
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Determination of sIgE to Ara h 6 is warranted in patients with a suspected peanut allergy
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especially in the absence of sensitisation to Ara h 1
,
2
,
3 and 9
Summary
Background Epidemiological studies have shown that the metabolic syndrome, a combination of type 2 diabetes mellitus, hypertension, dyslipidaemia and a high body mass index (BMI), occurs ...more frequently among adults who were born with a low birth weight. Because insulin is thought to play a key role in the pathogenesis of this syndrome we investigated insulin sensitivity and risk factors for cardiovascular disease in short prepubertal children born small for gestational age (SGA).
Patients and Methods Frequently sampled intravenous glucose tolerance tests (FSIGT) were performed in 28 short prepubertal children born SGA. Short stature was defined as a height < –2SD. SGA was defined as a birth length and/or a birth weight for gestational age < –2SD. Twelve short children born appropriate for gestational age (AGA) were used as controls for the FSIGT's results only. AGA was defined as a birth weight and/or birth length for gestational age > –2SD. In short SGA children, blood pressure (BP), fasting levels of serum free fatty acids (FFA), triglycerides (TG), total cholesterol (TC), high‐density lipoprotein (HDL) cholesterol and low‐density lipoprotein (LDL) were measured and compared to reference values.
Results Mean insulin sensitivity (Si) level in short SGA children was significantly reduced to 38% of the mean Si level measured in short AGA controls (P = 0·004). Mean acute insulin response (AIR) was significantly higher in SGA children compared to short AGA controls (P < 0·001). Differences in Si and AIR between the two groups remained significant after adjusting for age and BMI (P < 0·001 and P = 0·003, respectively). The mean (SD) systolic BP SDS was 1·3 (1,1), being significantly higher than zero. Mean fasting serum levels of FFA, TC, TG, HDL and LDL were all within the normal range. However, 6 of the 28 SGA children had serum FFA levels above the normal range. Cardiovascular risk factors could statistically be represented in two clusters. Both clusters played a significant role in the development of insulin insensitivity (1/Si).
Conclusion Although the metabolic syndrome has been described in adulthood, our study showed that risk factors for the development of type 2 diabetes mellitus and cardiovascular disease are already present during childhood in short prepubertal children born SGA, suggesting a pretype 2 diabetes mellitus phenotype.
Background
Allergic rhinitis and asthma are common and closely related diseases. Recently, a Portuguese questionnaire has been developed ‘The Control of Allergic Rhinitis and Asthma Test’ (CARATkids) ...that measures disease control of both diseases in children. This study aims to validate the CARATkids in Dutch children and for the first time in adolescents and, in addition, to calculate the minimal clinically important difference (MCID).
Methods
A prospective observational study was conducted in an outpatient clinic. After translation of the CARATkids from Portuguese to Dutch, patients (6–18 years) with asthma or asthma and allergic rhinitis completed the CARATkids, Asthma Control Test, and visual analog scale questionnaire three times. Baseline characteristics, mean scores, internal consistency, test–retest reliability, cross‐sectional and longitudinal validity, discriminative properties, responsiveness, and MCID of the CARATkids were assessed.
Results
A total of 111 patients were included. In total, 86% and 79%, respectively, completed the questionnaires at the second and third visits. All children had asthma, and 85% had concomitant allergic rhinitis. The internal consistency was good with all expected a priori correlations met. CARATkids scores were higher in patients with uncontrolled asthma and patients with moderate–severe rhinitis compared to better controlled subjects. Patients with a variable asthma control had significantly higher scores during periods of uncontrolled asthma. Also the Guyatt's responsiveness index was good. The MCID was 2.8.
Conclusions
The CARATkids questionnaire is a reliable and valid tool to assess allergic rhinitis and asthma control among Dutch children. The tool can be used in adolescents.
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•Discovery of a novel class of thyrotropin receptor antagonists.•A highly potent compound with oral efficacy was identified.•Risk of mutagenicity of compounds strongly ...reduced.•Efficacy correlates with exposure after oral dosing.
The thyrotropin receptor (TSH-R) regulates the thyroid gland and is normally activated by thyrotropin. In patients with Graves’ disease, TSH-R is also stimulated by stimulatory TSH-R autoantibodies leading to hyperthyroidism. In this paper, we describe the discovery of SYD5115 (67), a novel small molecule TSH-R antagonist with nanomolar potency. SYD5115 also blocks stimulating antibody induced synthesis of the thyroid hormone thyroxine (T4) in vivo, after a single oral dose. During optimization, several issues had to be addressed such as the low metabolic stability and the potential mutagenicity of our first series of compounds.
Researchers worldwide with information about the Kirsten ras (Ki-ras) tumour genotype and outcome of patients with colorectal cancer were invited to provide that data in a schematized format for ...inclusion in a collaborative database called RASCAL (The Kirsten ras in-colorectal-cancer collaborative group). Our results from 2721 such patients have been presented previously and for the first time in any common cancer, showed conclusively that different gene mutations have different impacts on outcome, even when the mutations occur at the same site on the genome. To explore the effect of Ki-ras mutations at different stages of colorectal cancer, more patients were recruited to the database, which was reanalysed when information on 4268 patients from 42 centres in 21 countries had been entered. After predetermined exclusion criteria were applied, data on 3439 patients were entered into a multivariate analysis. This found that of the 12 possible mutations on codons 12 and 13 of Kirsten ras, only one mutation on codon 12, glycine to valine, found in 8.6% of all patients, had a statistically significant impact on failure-free survival (P = 0.004, HR 1.3) and overall survival (P = 0.008, HR 1.29). This mutation appeared to have a greater impact on outcome in Dukes' C cancers (failure-free survival, P = 0.008, HR 1.5; overall survival P = 0.02, HR 1.45) than in Dukes' B tumours (failure-free survival, P = 0.46, HR 1.12; overall survival P = 0.36, HR 1.15). Ki-ras mutations may occur early in the development of pre-cancerous adenomas in the colon and rectum. However, this collaborative study suggests that not only is the presence of a codon 12 glycine to valine mutation important for cancer progression but also that it may predispose to more aggressive biological behaviour in patients with advanced colorectal cancer.
Background
Risk indicators of indolent systemic mastocytosis (ISM) in adults with clinical suspicion of ISM without accompanying skin lesions urticaria pigmentosa (UP) are lacking. This study aimed ...at creating a decision tree using clinical characteristics, serum tryptase, and the urinary histamine metabolites methylimidazole acetic acid (MIMA) and methylhistamine (MH) to select patients for bone marrow investigations to diagnose ISM.
Methods
Retrospective data analysis of all adults, in whom bone marrow investigations were performed to diagnose ISM, was carried out.
Results
In total, 142 patients were included. SM was absent in all 44 patients with tryptase <10 μg/l, in 45 of 98 (46%) patients with tryptase ≥10 μg/l and in 18 of 52 patients (35%) with tryptase >20 μg/l. Above 43 μg/l, all patients had ISM (n = 11). Male gender, insect venom anaphylaxis as presenting symptom, tryptase, MIMA, and MH were independent ISM predictors. If tryptase was ≥10 μg/l, the diagnostic accuracy of MIMA and MH was high (areas under the ROC curve 0.92).
Conclusions
In suspected patients without UP, the ISM risk is very low (if present at all) if tryptase is <10 μg/l. If tryptase is ≥10 μg/l, this risk depends on MIMA and MH, being low if these are normal, but high if these are elevated. Male gender and insect venom anaphylaxis are additional risk indicators. We recommend refraining from bone marrow examinations in suspected patients without UP if tryptase is <10 μg/l. Our results question the reliability of the minor diagnostic World Health Organization criterion of tryptase >20 μg/l.
Summary
background To investigate in a group of short children born small for gestational age (SGA), the effects of 3 years of GH treatment vs. no treatment on bone age (BA), height and bone mineral ...density (BMD). Also, to evaluate the influence of the severity of growth retardation at start and the GH dose on the gain in height.
patients and methods The study design was an open‐labelled, controlled multicentre GH study for 3 years. Non‐GH‐deficient (GHD) children (n = 87) were randomized to either a GH group (n = 61) or an untreated control group (n = 26). In addition, 12 SGA children had GHD (GHD group) and were treated in parallel. Both the GH and the GHD group were treated with a GH dose of 33 µg/kg/day. BMD was evaluated using dual energy X‐ray absorptiometry (DEXA). In addition, data of our first GH trial in which short SGA children were treated with a GH dose of 66 µg/kg/day (n = 24) were used for comparison of height gain.
results In contrast to the control group, the GH group showed a significant increase in height (P < 0·001), as did the parallel GHD group. Bone maturation Δ bone age (BA)/Δ calendar age (CA) increased significantly during the first 2 years of GH treatment but slowed‐down thereafter. The 3‐year ΔBA/ΔCA ratio correlated significantly with the gain in height (r = 0·6, P < 0·001). At start, mean BMD SDS and mean BMAD SDS were significantly lower than zero. During GH treatment both increased impressively (P < 0·001). The gain in height of children with severe short stature at start (≤ −3·00 SDS), did not differ between those receiving either a GH dose of 33 or 66 µg/kg/day.
conclusion Three years of GH treatment in short children born SGA results in a normalization of height during childhood. Also, bone maturation increased proportionately to the height gain. At start, mean values of BMD and BMAD were significantly reduced but normalized during GH treatment. We did not find an indication to treat very short SGA children (H SDS ≤−3·00) with a higher GH dose. We rather suggest to start GH treatment at an early age in order to achieve a normal height before puberty starts.
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