A further evaluation of the clinical use of specific IgE antibody testing in allergic diseases

BACKGROUND: The evaluation and interpretation of the results from blood tests measuring specific immunoglobulin E (IgE) antibody concentration is currently made using the dichotomized result from the test despite a quantitative result is obtained. It has been shown that different levels of IgE antibodies, assessed by blood test and skin prick test, may have a relation to presence of symptoms, implying that there is more information in a quantitative result than in the dichotomous--positive or negative. OBJECTIVE: To investigate the clinical utility of quantification of IgE antibodies in the diagnosis of allergic patients and whether such procedure has any advantage to the presently dichotomously used sensitivity and specificity at a fixed cut-off. METHODS: Data from a previously published study (R. Paganelli, I.J. Ansoteugi, J. Sastre, C.-E. Lange, M.H.W.M. Roovers, H. de Groot, N.B. Lindholm, P.W. Ewan, Allergy, 1998; 53) analysing diagnosis of allergic patients in four different clinics were re-evaluated. In the original study consecutive patients with suspected IgE-mediated allergy had been examined and evaluated according to the clinical routine at each clinic, using case history, physical examination, skin tests and laboratory tests, except the test to be evaluated, and given a "doctors' allergen-specific diagnosis" as positive or negative. In the present study the relation between "doctors' allergen-specific diagnosis", expressed as pos/neg, and the quantitative levels of specific IgE antibody concentration was analysed using a logistic regression model. This presentation of results was also compared with the more common characteristics of sensitivity and specificity, and also with Receiver-operator characteristics (ROC) curves. RESULTS: The used logistic model described the relationship between allergen-specific diagnosis in each study and the levels of IgE antibodies. The shape of the curve illustrated the physicians' disposition for a positive diagnose in the study, in relation to the specific IgE antibody level. Differences in the shape of the curve was found both between allergens within clinics and between clinics for the same allergen. No association could be demonstrated between prevalence and shape of the curve. CONCLUSIONS: Conventional sensitivity/specificity figures or ROC concepts only use the qualitative statement of whether IgE is present or not. A risk assessment using the quantitative level of IgE antibody to an allergen increases the utility of the information in clinical context compared with a qualitative statement of whether IgE is present or not. The quantification demonstrated the link between specific IgE antibodies and allergic reactions. The use of objective, well performing quantitative tests should help improve diagnostic accuracy and might provide a way for the patient to understand and manage his or her daily situation and risk for reactions.     

Monocyte and neutrophil recruitment during oral Salmonella infection is driven by MyD88‐derived chemokines

Oral Salmonella infection recruits phagocytes to Peyer's patches (PP) and MLN. The chemokines induced in infected PP and MLN, the cellular sources during infection and the TLR signaling pathways involved in vivo are not known. Here, we show that CCL2, CXCL9 and CXCL2 mRNA are up‐regulated in PP and MLN coincident with the first arrival of monocytes and neutrophils. Laser capture microdissection microscopy revealed that chemokine mRNA up‐regulation was differently distributed in PP. Despite this, recruited monocytes and neutrophils formed inflammatory cell clusters throughout PP. Monocytes and neutrophils purified from infected mice preferentially produced CXCL2 and small amounts of CCL2, and neutrophils from infected mice migrated towards CXCL2 and CCL3. Furthermore, phagocyte recruitment to PP and MLN was intact in mice lacking TLR4 alone and when signaling through TLR4 and TLR5 was simultaneously absent; however, recruitment was compromised in MyD88^?/? and more so in MyD88^?/?TLR4^?/? double knockout mice. Phagocyte release into the blood, however, was only marginally reduced in MyD88^?/?TLR4^?/? mice. Defective phagocyte recruitment to PP and MLN of MyD88^?/?TLR4^?/? mice was paralleled by low chemokine induction. These data provide insight into the chemokines and TLR signaling pathways that orchestrate the early phagocyte response to oral Salmonella infection.     

Micro‐arrayed wheat seed and grass pollen allergens for component‐resolved diagnosis

Background: Wheat is a potent allergen source and can cause baker’s asthma, food and pollen allergy. The aim of the study was to develop an allergen micro‐array for differential diagnosis of baker’s asthma, wheat‐induced food allergy and grass pollen allergy. Methods: We analysed the immunoglobulin‐E reactivity profiles of patients suffering from baker’s asthma, wheat‐induced food allergy and grass pollen allergy to micro‐arrayed recombinant wheat flour allergens and grass pollen allergens and compared these results with clinical results and diagnostic tests based on crude wheat flour, wheat pollen and grass pollen allergen extracts. Results: We identified recombinant wheat flour allergens, which are specifically recognized by patients suffering from baker’s asthma, but not from patients with food allergy to wheat or pollen allergy. rPhl p 1 and rPhl p 5 were identified as marker allergens specific for grass pollen allergy. They can be used to replace grass pollen extracts for allergy diagnosis and to identify grass pollen allergic patients among patients suffering from baker’s asthma and wheat‐induced food allergy. Profilin was identified as a cross‐reactive allergen recognized by patients suffering from baker’s asthma, food and pollen allergy. Conclusions: Our results indicate that it will be possible to design serological tests based on micro‐arrayed recombinant wheat seed and grass pollen allergens for the discrimination of baker’s asthma, wheat‐induced food allergy and grass pollen allergy.     

Evaluation of fetal serum thiol/disulphide homeostasis in deliveries complicated by nuchal cord

Aim: To investigate the serum thiol/disulphide homeostasis in deliveries complicated by nuchal cord (NC) and to compare the results with healthy deliveries (without NC).

Methods: This prospective controlled study included 48 pregnant women complicated by NC and 48 similar gestational aged healthy pregnant women during labor. Fetal umbilical cord serum samples were collected during labor and the thiol/disulphide homeostasis was measured by using an automated assay method. The patients were followed up until end of the delivery and perinatal outcomes were recorded.

Results: Fetal umbilical cord native thiol, total thiol, and disulphide levels as well as disulphide/native thiol and disulphide/total thiol ratios are impaired in labor with the presence of NC. There were no statistically significant differences in terms of maternal and gestational age at delivery and maternal number of gravida and parity, fetal gender, fifth Apgar scores <7, mode of delivery and fetal birth weight between groups. The group of patients with NC had higher emergency C/S numbers indicated for fetal distress and lower first Apgar scores <7. There were no neonatal intensive care unit admissions among these babies.

Conclusions: Maternal serum thiol/disulphide homeostasis reflect transient effects of NC during labor regardless of labor type. Vaginal delivery can be safely and successfully performed in pregnancies complicated with NC.     

Inflammatory marker YKL-40 levels in intrahepatic cholestasis of pregnancy

Intrahepatic cholestasis of pregnancy is a diagnosis of exclusion and presents with unexplained pruritus, abnormal liver function tests, and increased serum bile acid levels, particularly in the third trimester of pregnancy. Serum YKL-40 levels are increased in liver diseases and our aim was to investigate YKL-40 levels in pregnant women with ICP. 40 women with intrahepatic cholestasis of pregnancy and 40 healthy pregnant women were included in this cross-sectional study. Serum YKL-40 levels were measured in both groups and correlation analysis were performed between the YKL-40 and other liver function tests. Serum YKL-40 concentrations were higher in the intrahepatic cholestasis of pregnancy group than in the control group (103.46?±?53.03 vs. 57.60?±?30.30?ng/ml, p?=?.002). The cutoff YKL-40 serum concentration was 84.80?ng/ml for the diagnosis of intrahepatic cholestasis of pregnancy. There was no correlation between fasting bile acids and YKL-40 levels. However, there was a significant positive correlation between the YKL-40 levels and aspartate aminotransferase (r?=?0.22, p?=?.04) and alanine aminotransferase (r?=?0.24, p?=?.02). Raised YKL-40 levels might support the evidence on inflammatory processes in intrahepatic cholestasis of pregnancy.     

Epigenetic modulation at birth – altered DNA-methylation in white blood cells after Caesarean section

Aim:  Delivery by C-section (CS) has been associated with increased risk for allergy, diabetes and leukaemia. Whereas the underlying cause is unknown, epigenetic change of the genome has been suggested as a candidate molecular mechanism for perinatal contributions to later disease risk. We hypothesized that mode of delivery affects epigenetic activity in newborn infants.
Methods:  A total of 37 newborn infants were included. Spontaneous vaginal delivery (VD) occurred in 21, and 16 infants were delivered by elective CS. Blood was sampled from the umbilical cord and 3–5 days after birth. DNA-methylation was analyzed in leucocytes.
Results:  Infants born by CS exhibited higher DNA-methylation in leucocytes compared with that of those born by VD (p < 0.001). After VD, newborn infants exhibited stable levels of DNA-methylation, as evidenced by comparing cord blood values with those 3–5 days after birth (p = 0.55). On postnatal days 3–5, DNA-methylation had decreased in the CS group (p = 0.01) and was no longer significantly different from that of VD (p = 0.10).
Conclusion:  DNA-methylation is higher in infants delivered by CS than in infants vaginally born. Although currently unknown how gene expression is affected, or whether epigenetic differences related to mode of delivery are long-lasting, our findings open a new area of clinical research with potentially important public health implications.     

A randomized intervention since infancy to reduce intake of saturated fat: calorie (energy) and nutrient intakes up to the age of 10 years in the Special Turku Coronary Risk Factor Intervention Project

OBJECTIVE: To evaluate the longitudinal impact of dietary counseling on children's nutrient intake. DESIGN: A prospective, randomized, clinical trial. PARTICIPANTS: Children were recruited to the study between December 1, 1989, and May 30, 1992. At the age of 7 months, children were randomized to the intervention group (n = 540) or the control group (n = 522) and were followed up until the age of 10 years.Intervention Families in the intervention group have, since randomization, received regularly individualized counseling about how to modify the quality and quantity of fat in the child's diet, the goal being an unsaturated-saturated fat ratio of 2:1. MAIN OUTCOME MEASURES: Nutrient intakes between the ages of 4 and 10 years based on annual 4-day food records. RESULTS: The fat intake of the intervention children was constantly around 30% of the calorie (energy) intake, while that of the control children was 2 to 3 calorie percentage units higher (P<.001). The intervention children received 2 to 3 calorie percentage units less saturated fats and 0.5 to 1.0 calorie percentage unit more polyunsaturated fats than the control children (P<.001 for both). However, neither group reached the 2:1 goal set for the unsaturated-saturated fatty acid ratio. The vitamin and mineral intakes of the intervention and control children closely resembled each other despite the marked differences in fat intake. CONCLUSION: Individualized, biannually given, fat intake-focused dietary counseling that began at the child's age of 8 months continued to influence favorably the diet of 4- to 10-year-old intervention children without disadvantageous dietary effects, but the 2:1 goal for unsaturated-saturated fat ratio was not reached.     

Effect of physical training on mitochondrial respiration and reactive oxygen species release in skeletal muscle in patients with obesity and type 2 diabetes

Aim/hypothesis  

Studies have suggested a link between insulin resistance and mitochondrial dysfunction in skeletal muscles. Our primary aim was to investigate the effect of aerobic training on mitochondrial respiration and mitochondrial reactive oxygen species (ROS) release in skeletal muscle of obese participants with and without type 2 diabetes.     

Preparation of Multi-Walled Carbon Nanotube/Amino-Terminated Ionic Liquid Arrays and Their Electrocatalysis towards Oxygen Reduction

Arrays of aligned multi-walled carbon nanotube-ionic liquid (MIL) were assembled on silicon wafers (Si-MIL). Formation of Si-MIL was confirmed by FTIR, AFM and Raman techniques. The electrochemical measurements indicated that Si-MIL showed good electrocatalysis towards oxygen reduction compared with MIL drop-cast on a glassy carbon electrode.