Regulation of immune responses to Strongyloides venezuelensis challenge after primary infection with different larvae doses

Nematode infections are generally followed by high rates of reinfection, leading to elevated prevalence in endemic areas. Therefore, the effective control of nematode infections depends on understanding the induction and regulation of protective mechanisms. However, most experimental models for protective immune response against nematodes use high parasite exposure, not always reflecting what occurs naturally in human populations. In this study, we tested whether infecting mice with different Strongyloides venezuelensis larvae loads would affect protective responses against reinfection. Interestingly, we found that a previous infection with 10–500 larvae conferred high rate of protection against reinfection with S. venezuelensis in mice, by destroying large numbers of migrating larvae. However, low‐dose priming did not abolish adult worm maturation, as detected in high‐dose primed group. Results also indicated that a previous low‐dose infection delayed the development of cellular infiltrate, while a high inoculum rapidly induced these inflammatory features. Cytokine production by splenocyte cultures of challenge infected mice demonstrated that low‐dose priming had increased production of IL‐4 and IFN‐γ, while high‐dose induced IL‐4 production but not IFN‐γ. Our data support the hypothesis that low‐dose nematode infection does not induce a polarized type‐2 immune response, allowing adult worm survival.     

Sesame food allergy and sensitization in children: the natural history and long-term follow-up

Sesame food allergy (SFA) in children is an increasingly recognized one in many countries. Our objective was to describe the course and natural history of SFA. Seventy-four patients sensitized to sesame were evaluated using clinical records, questionnaires, skin prick tests (SPT), in vitro specific immunoglobulin (sIg) E, and oral challenges (OC) and categorized into three groups: group A: patients who experienced allergic reaction after ingestion of sesame-containing food (n = 45); group B: patients evaluated for atopic dermatitis and found to be sesame SPT-positive (n = 11); group C: patients with sensitization to sesame allergen (n = 18). Group A patients were followed for an average of 6.7 yr. Analysis of our results revealed that 76% of patients in group A developed the allergy by the age of 2. The median age at onset of allergy in these patients was 1 yr. Immediate reaction to a minimal amount of sesame was characteristic. Skin was the most common site of involvement, followed by respiratory and gastrointestinal systems. Tolerance developed in only 20% of the patients. High sIgE (>0.15 IU) was demonstrated only in 75% of those in which it was examined. Sixteen patients performed oral sesame food challenge which was found positive in 88%. No correlation was found between the size of SPT and the level of in vitro sesame IgE antibodies, the outcome of OC results, and the development of tolerance to sesame. In conclusion, SFA tends to appear early in life, but unlike cow's milk and egg allergy, persists in 80% of the cases. Typical reactions combined with positive sesame SPT are reliable for diagnosis.     

Psychosocial maternal stress during pregnancy affects serum corticosterone, blood immune parameters and anxiety behaviour in adult male rat offspring

Exposure to prenatal stress can impair the behavioural and hormonal development in mammals. However, the consequences for the immune system are rarely investigated and there is only limited evidence that naturalistic prenatal stressors do also have the potential to affect the offspring. Thus, by using a social conflict model in female Long-Evans rats, we investigated the effects of prenatal social stress on several behavioural, hormonal and immunological parameters. Offspring from stressed and non-stressed pregnant females were housed in pairs after weaning, and tested at an age of 4-6 months. Prenatally stressed (PS) males were more active in the elevated plus-maze test as indicated by significantly more frequent entries into the open arms compared to prenatal control males (PC). In addition, PS males had significantly lower serum corticosterone concentrations under basal conditions as well as after ACTH-challenge. The basal number of total leukocytes was significantly lower in the PS group due to significantly lower lymphocyte counts. In particular, the CD4+ T-helper cell subset was affected. The lymphocyte proliferation to pokeweed mitogen was lower in PS males. Because some of the present findings do not correspond to previous studies using conventional stressors, we assume that the nature of the stressor plays an important role for pregnancy outcome and behaviour and physiology of the offspring in later life.     

儿童先天性蔗糖酶-异麦芽糖酶缺乏症3例

目的:探讨儿童先天性蔗糖酶-异麦芽糖酶缺乏症（CSID）的诊断与治疗。方法:总结3例诊断为CSID患儿的临床特点、诊断和治疗结果。结果:3例患儿年龄1岁4个月至1岁7 个月,单纯母乳喂养期间大便正常,断母乳改奶粉喂养、添加米糊、粥后开始腹泻,粪便为黄色稀水样、稀糊样,每天7～10次。入院查体均有蛋白质-热能营养不良。3例蔗糖激发试验结果显示,同餐前血糖相比,餐后血糖最大升高值(％)分别为0.1(2.0%)、0.1（2.6%）和0.9（19.1%） mmol·L-1,并出现排黄色稀水样粪便;葡萄糖激发试验结果显示,同餐前血糖相比,餐后血糖最大升高值（％）分别为1.5（30.6%）、2.3（65.7%）和4.4（107%）mmol·L-1,均未出现腹泻。3例患儿诊断CSID后停用蔗糖和淀粉类食物,1～2 d后粪便性状和次数恢复正常。结论:临床上疑诊CSID患儿,可根据典型的病史特点（断母乳后出现腹泻）,回避蔗糖和淀粉类饮食后腹泻迅速缓解,蔗糖激发试验阳性可作出临床诊断。     

The predictive value of skin prick testing for challenge-proven food allergy: a systematic review

Immunoglobulin E-mediated (IgE) food allergy affects 6-8% of children, and the prevalence is believed to be increasing. The gold standard of food allergy diagnosis is oral food challenges (OFCs); however, they are resource-consuming and potentially dangerous. Skin prick tests (SPTs) are able to detect the presence of allergen-specific IgE antibodies (sensitization), but they have low specificity for clinically significant food allergy. To reduce the need for OFCs, it has been suggested that children forgo an OFC if their SPT wheal size exceeds a cutoff that has a high predictability for food allergy. Although data for these studies are almost always gathered from high-risk populations, the 95% positive predictive values (PPVs) vary substantially between studies. SPT thresholds with a high probability of food allergy generated from these studies may not be generalizable to other populations, because of highly selective samples and variability in participant's age, test allergens, and food challenge protocol. Standardization of SPT devices and allergens, OFC protocols including standardized cessation criteria, and population-based samples would all help to improve generalizability of PPVs of SPTs.     

Treatment with inhaled formulation of angiotensin-(1-7) reverses inflammation and pulmonary remodeling in a model of chronic asthma

Asthma is characterized by inflammation, pulmonary remodeling and bronchial hyperresponsiveness. We have previously shown that treatment with angiotensin-(1-7) [Ang-(1-7)] promotes resolution of eosinophilic inflammation and prevents chronic allergic lung inflammation. Here, we evaluated the effect of treatment with the inclusion compound of Ang-(1-7) in hydroxypropyl β-cyclodextrin (HPβCD) given by inhalation on pulmonary remodeling in an ovalbumin (OVA)-induced chronic allergic lung inflammation. Mice were sensitized to ovalbumin (OVA; 4 injections over 42 days, 14 days apart) and were challenged 3 times per week, for 4 weeks (days 21–46). After the 2nd week of challenge, mice were treated with Ang-(1-7) by inhalation (4.5 μg of Ang-(1-7) included in 6.9 μg of HPβCD for 14 days, i.e. days 35–48). Mice were killed 72 h after the last challenge and blood, bronchoalveolar lavage fluid (BALF) and lungs were collected. Histology and morphometric analysis were performed in the lung. Metalloproteinase (MMP)-9 and MMP-12 expression and activity, IL-5, CCL11 in the lung and plasma IgE were measured. After 2 weeks of OVA challenge there was an increase in plasma IgE and in inflammatory cells infiltration in the lung of asthmatic mice. Treatment with inhaled administration of Ang-(1-7)/HPβCD for 14 days reduced eosinophils, IL5, CCL11 in the lung and plasma IgE. Treatment of asthmatic mice with Ang-(1-7)/HPβCD by inhalation reversed pulmonary remodeling by reducing collagen deposition and MMP-9 and MMP-12 expression and activity. These results show for the first time that treatment by inhalation with Ang-(1-7) can reverse an installed asthma, inhibiting pulmonary inflammation and remodeling.     

Sensitivity and specificity of specific IgE,skin prick test and atopy patch test in examination of food allergy

The aim of this study is the evaluation of the specificity and sensitivity of the skin prick tests (SPTs), specific IgE and atopy patch tests (APTs) in atopic dermatitis patients suffering from food allergy. A total of 301 patients were examined, complete dermatological and allergological examination was performed in all patients. The food allergy was confirmed to peanuts in 62 patients (20%), to egg in 16 patients (5%), to soy in 9 patients (3%), to wheat in 12 patients (4%) and to cow milk in 6 patients (2%). The specificity of SPT, specific IgE and APT is considered as good; the sensitivity of APT is low. The positive results in isolation cannot confirm the food allergy; however, together with other diagnostic methods, such as clinical history and open exposure test, these tests are valuable tool in examination of food allergy.     

Lower airway inflammatory responses to repeated very-low-dose allergen challenge in allergic rhinitis and asthma

BACKGROUND: Low-dose allergen challenge (LDAC) may be a useful tool for studying the capacity of allergens to induce airway inflammation in atopic subjects. OBJECTIVE: To evaluate lower airway inflammatory changes following repeated inhalation of very low doses of allergen (VLDAC) in non-asthmatic subjects with allergic rhinitis (NAAR) compared with mild allergic asthmatic subjects (AA). METHODS: Fourteen NAAR and 11 AA were seen out of the pollen season and had skin prick tests with common aeroallergens. Baseline spirometry (S) and methacholine challenge (MC) were done and blood and induced sputum (IS) differential cell counts were obtained. Each subject underwent VLDAC on four consecutive mornings with a relevant allergen. S, MC, and blood and IS samplings were repeated 6 h after the second and fourth VLDAC and one week later. RESULTS: Although there were, as expected, no changes in FEV1 or PC20 in either group, mean percentage eosinophils on IS were significantly increased in NAAR on day 2 of VLDAC and decreased in all but one subject on day 4, with a tendency to return to baseline levels one week later. In AA, there was a non-significant trend for sputum eosinophils to increase on day 2; four subjects showed a decrease of eosinophils on day 4 of VLDAC. There was a correlation between eosinophil cationic protein (ECP) levels and eosinophil counts in NAAR throughout the study. There were no variations in other sputum cells or blood inflammatory cells. CONCLUSION: VLDAC can increase the percentage of eosinophils in IS of NAAR subjects without associated respiratory symptoms nor physiological modifications. A reduction in eosinophilic response despite repeated exposure, more common in NAAR subjects, suggests an adaptation process that needs to be further evaluated.     

Utility of the ratio of food-specific IgE/total IgE in predicting symptomatic food allergy in children

BACKGROUND: Double-blind, placebo-controlled food challenges are time-consuming, expensive and not without risk to patients. Therefore, an in vitro test that could accurately diagnose food allergy would be of great value. OBJECTIVE: To evaluate the utility of the ratio of specific immunoglobulin E (IgE)/total IgE compared with specific IgE (sIgE) alone in predicting symptomatic food allergy. METHODS: We retrospectively analysed 992 controlled oral food challenges performed in 501 children (median age 13 months). The ratio of sIgE/total IgE was calculated and tested for correlation with the outcome of food challenges. Receiver operator characteristics (ROC)-curves were performed; predicted probabilities and predictive decision points were calculated. RESULTS: A significant correlation was found between the ratio and the outcome of food challenges for cow's milk (CM), hen's egg (HE), and wheat, but not for soy. The ROC and predicted probability curves as well as sensitivity and specificity of the decision points of the ratio were similar to those of sIgE levels for CM, HE and wheat. CONCLUSION: In view of the greater effort needed to determine the ratio, without benefit compared with the sIgE alone, the calculation of the ratio of sIgE/total IgE for diagnosing symptomatic food allergy offers no advantage for CM, HE, wheat or soy. For the majority of cases controlled oral food challenges still remain the method of choice.