Severity Of Allergic Symptoms Research Articles

The addition of CpG to alum-adjuvanted vaccines provides a bystander effect that reduces the severity of peanut allergy in mice. (HYP7P.311)

Abstract Rationale: The “hygiene hypothesis” predicts that a “clean” environment increases the risk of developing allergic disease while endotoxin exposure is protective. The vaccine adjuvant alum may alter immune responses to enhance the induction or severity of allergic disease. A mouse model of peanut allergy was utilized to determine if endotoxin or alum exposure influence the severity of allergic disease. Methods: C3H/HeN mice were housed in high or low endotoxin environments. Mice received three biweekly ovalbumin (Ova) immunizations adjuvanted with alum or alum combined with MPL or CpG 1826. Peanut sensitization was achieved by gastric gavage of peanut and cholera toxin weekly for 4 weeks beginning one day after immunization with Ova + adjuvants. One week after the last immunization all mice were challenged with peanut and monitored for hypothermia and allergy clinical symptoms. Results: Mice immunized with Ova + Alum + CpG exhibited mild allergic symptoms after peanut challenge (-2.0°C and 1.8 score) that did not statistically differ from challenged unsensitized mice (0.68°C and 0 score). All other immunization groups exhibited severe allergic symptoms after challenge (< -2.5°C and >2.5 score) and were significantly different when compared to challenged unsensitized mice. Conclusion: Endotoxin and alum exposure did not increase the severity of peanut allergy. The addition of CpG 1826 to the Ova + Alum vaccine reduced the severity of peanut-specific allergic disease.

Relationships between IgE/IgG4 Epitopes, Structure and Function in Anisakis simplex Ani s 5, a Member of the SXP/RAL-2 Protein Family

BackgroundAnisakiasis is a re-emerging global disease caused by consumption of raw or lightly cooked fish contaminated with L3 Anisakis larvae. This zoonotic disease is characterized by severe gastrointestinal and/or allergic symptoms which may misdiagnosed as appendicitis, gastric ulcer or other food allergies.The Anisakis allergen Ani s 5 is a protein belonging to the SXP/RAL-2 family; it is detected exclusively in nematodes. Previous studies showed that SXP/RAL-2 proteins are active antigens; however, their structure and function remain unknown.The aim of this study was to elucidate the three-dimensional structure of Ani s 5 and its main IgE and IgG4 binding regions.Methodology/Principal FindingsThe tertiary structure of recombinant Ani s 5 in solution was solved by nuclear magnetic resonance. Mg2+, but not Ca2+, binding was determined by band shift using SDS-PAGE. IgE and IgG4 epitopes were elucidated by microarray immunoassay and SPOTs membranes using sera from nine Anisakis allergic patients.The tertiary structure of Ani s 5 is composed of six alpha helices (H), with a Calmodulin like fold. H3 is a long, central helix that organizes the structure, with H1 and H2 packing at its N-terminus and H4 and H5 packing at its C-terminus. The orientation of H6 is undefined. Regarding epitopes recognized by IgE and IgG4 immunoglobulins, the same eleven peptides derived from Ani s 5 were bound by both IgE and IgG4. Peptides 14 (L40-K59), 26 (A76-A95) and 35 (I103-D122) were recognized by three out of nine sera.Conclusions/SignificanceThis is the first reported 3D structure of an Anisakis allergen. Magnesium ion binding and structural resemblance to Calmodulin, suggest some putative functions for SXP/RAL-2 proteins. Furthermore, the IgE/IgG4 binding regions of Ani s 5 were identified as segments localized on its surface. These data will contribute towards a better understanding of the interactions that occur between immunoglobulins and allergens and, in turn, facilitate the design of novel diagnostic tests and immunotherapeutic strategies.

携帯用患者家族向けアレルギー症状の重症度評価と対応マニュアルの作成および評価

携帯用患者家族向けアレルギー症状の重症度評価と対応マニュアルの作成および評価

Attention deficit hyperactivity disorder like behavioral problems and parenting stress in pediatric allergic rhinitis.

ObjectivePrevious studies have reported comorbidity of attention deficit and hyperactivity disorder (ADHD) and allergic diseases. The current study investigated ADHD like behavioral symptoms and parenting stress in pediatric allergic rhinitis.MethodsEighty-seven children (6-13 years old) with allergic rhinitis and 73 age- and sex-matched children of control group were recruited. Diagnosis and severity assessments of allergic rhinitis were determined by a pediatric allergist. The Parenting Stress Index-Short Form (PSI-SF), ADHD Rating Scale (ARS), and Child Behavior Checklist (CBCL) were completed by their mothers.ResultsIn the allergic rhinitis group, the total PSI-SF score (p<0.01), ARS score (p<0.01), the subscale scores of the CBCL including somatization, attentional problems and emotional instability (p=0.01; p<0.01; p<0.01) and prevalence of ADHD (p=0.03) were significantly higher than those of the control group. Among mothers of children with allergic rhinitis, those of children with comorbid ADHD demonstrated significantly higher parenting stress than those without comorbid ADHD (p<0.01). Parenting stress was correlated with severity of child's allergic symptoms and the ARS total score (beta=0.50, p<0.01; beta=0.39, p<0.01). There was a significant correlation between allergic symptom severity and the ARS total score (B=8.4, SD=2.5, t=3.3, p<0.01).ConclusionThis study demonstrated that ADHD symptoms were common in children with allergic rhinitis, and this factor increased parenting stress and disrupted the parent-child relationship. Routine evaluation and early management of ADHD symptoms in pediatric allergic rhinitis may benefit families of children with allergic rhinitis.

Anti-rPru p 3 IgE Levels Are Inversely Related to the Age at Onset of Peach-Induced Severe Symptoms Reported by Peach-Allergic Adults

Sensitisation to peach lipid transfer protein (LTP; Pru p 3) is significantly associated with severe allergic symptoms in adults, but little is known about the age at onset of peach allergy. We investigated a possible correlation between specific IgE levels to Pru p 3 and the age at onset of peach allergy. One hundred and forty-eight patients allergic to peach were divided into 6 classes according to the age at onset. Sera were analyzed for IgE antibodies to peach, rPru p 3, rPru p 1, rPru p 4, rBet v 1, rBet v 2, total IgE titre, and tryptase; all collected data were statistically analysed. A significant inverse correlation was found between the age at onset of peach allergy and anti-rPru p 3 IgE levels at diagnosis (p < 0.0005; Spearman's ρ = -0.3833). In contrast, the age at onset was directly correlated with both anti-rPru p 1 IgE levels (p = 0.0001; Spearman's ρ = 0.3197) and anti-rBet v 1 IgE levels (p = 0.0006; Spearman's ρ = 0.2914) at diagnosis. No correlations were detected between the reported age at onset and anti-peach, anti-rPru p 4, anti-rBet v 2 IgE and total IgE values and serum tryptase levels. At diagnosis, when peach allergy starts at a younger age, it is likely associated with Pru p 3 sensitisation, and the younger the onset, the higher the IgE titres. When peach allergy starts at an older age, it is more likely the result of cross-reactivity to Bet v1.

Health sector costs of self-reported food allergy in Europe: a patient-based cost of illness study

Food allergy is a recognized health problem, but little has been reported on its cost for health services. The EuroPrevall project was a European study investigating the patterns, prevalence and socio-economic cost of food allergy. To investigate the health service cost for food-allergic Europeans and the relationship between severity and cost of illness. Participants recruited through EuroPrevall studies in a case-control study in four countries, and cases only in five countries, completed a validated economics questionnaire. Individuals with possible food allergy were identified by clinical history, and those with food-specific immunoglobulin E were defined as having probable allergy. Data on resource use were used to estimate total health care costs of illness. Mean costs were compared in the case-control cohorts. Regression analysis was conducted on cases from all 9 countries to assess impact of country, severity and age group. Food-allergic individuals had higher health care costs than controls. The mean annual cost of health care was international dollars (I$)2016 for food-allergic adults and I$1089 for controls, a difference of I$927 (95% confidence interval I$324-I$1530). A similar result was found for adults in each country, and for children, and was not sensitive to baseline demographic differences. Cost was significantly related to severity of illness in cases in nine countries. Food allergy is associated with higher health care costs. Severity of allergic symptoms is a key explanatory factor.

Novel Approaches to Food Allergy

Food allergies have increased in recent decades. However, they cannot be effectively treated by the current management, which is limited to the identification and avoidance of foods that induce allergies and to the use of medicines for symptoms relief. To meet the medical need of prevention and cure of food allergies, several therapeutic strategies are under investigation. Some newly developed biologics such as anti-IgE antibody and anti-interleukin (IL)-5 antibody directed against significant molecules in the allergic process have shown their potential for the treatment of food allergies. Allergen-specific immunotherapy is the therapy that induces immune tolerance and may reduce the need for conventional medication, severity of allergic symptoms and eliminate hypersensitivity. In this article, clinical studies of immunotherapy via subcutaneous, oral, sublingual, and epicutaneous routes are extensively reviewed for their safety and effectiveness on various food allergies. In addition, to reduce the risk of anaphylaxis and increase toleragenic immunity, many studies are focusing on the modification of traditional allergens used for immunotherapy. Moreover, a Chinese herbal formulation with potential anti-allergic effects is being evaluated for its efficacy in patients with peanut allergy. Although more studies are needed, accumulated data of current studies represent compelling evidence of curative effects of some strategies and give a hope that food allergies are likely to be successfully treated in the future.

Fennel Allergy Is a Lipid-Transfer Protein (LTP)-Related Food Hypersensitivity Associated with Peach Allergy

Fennel allergy has been rarely reported, and the association with peach allergy has never been described. Our aim was to (i) study the correlation between symptom severity of peach and fennel and (ii) identify fennel allergens and the role of rPru p 3 antibodies in severe reactions to fennel. In 148 patients with peach allergy, we investigated 58 patients with symptoms and IgE antibodies positive to fennel. IgE to rPru p 1, 3, and 4 and rBet v 1, 2, and 4 were measured by immunoblotting, and the N-terminal amino acid sequences and relevant allergens were determined. We found significant association between severe reactions to fennel and peach (p = 0.0009). A major allergen was ~9 kDa lipid-transfer protein (LTP), cross-reactive with Pru p 3, a 15 kDa protein identified as a pathogenesis-related protein 1 of the Bet v 1 family. In conclusion, peach and fennel severe allergic symptoms are significantly related, and LTP is a major fennel allergen. Fennel should be included in the LTP syndrome.

Association between allergic rhinitis and asthma in a Northern Alberta cohort

BackgroundMany published epidemiologic studies confirm a marked increase in the prevalence of asthma and allergic rhinitis. The link between allergic rhinitis and asthma has been extensively studied and approximately 75% of patients with asthma have allergic rhinitis. The proportion of patients with asthma in populations of allergic rhinitis patients has not been well studied.ObjectiveThe purpose of this study is to estimate the prevalence of undiagnosed asthma in a specific population of patients presenting to an Otolaryngologist with symptoms of allergic rhinitis.Study designProspective cohort study. Methods: Patients presenting with symptoms of allergic rhinitis to two tertiary care Rhinology practices in Northern Alberta were asked to undergo allergy skin testing, serum IgE quantification, and pulmonary functional testing. Patients with previous asthma screening or known history of reactive airway disease or asthma were excluded.Results107 patients with allergic rhinitis symptoms were recruited between September 2010 to January 2013. Patients predominantly had perennial or persistent rhinitis (64.5%) with moderate-severe symptoms (50.5%). While only 14.9% of patients had abnormal IgE levels, 68.8% had positive skin testing. Abnormal pulmonary function tests were obtained in 39.1% of patients and 26.1% of patients were diagnosed with asthma.ConclusionsThere is a high prevalence of undiagnosed asthma in patients presenting to tertiary Rhinology care with moderate to severe allergic rhinitis symptoms. Screening lung function testing should be considered in this patient population.

Health outcomes, education, healthcare delivery and quality – 3050. A survey of severe allergic symptoms among children in a disaster-hit area: A challenge of Tohoku Medical Megabank Organization

On March 11, 2011, the Tohoku region and some prefectures along the Pacific coast of Japan were hit by the Great East Japan Earthquake. Past experiences of tsunami in other countries also raised concern about the health of the local people after the disaster. To monitor the health status of people living in Miyagi prefecture and to ensure sufficient quality of healthcare for them, Tohoku University has established the Tohoku Medical Megabank Organization (ToMMo). We plan to conduct three cohort studies of schoolchildren, three-generation families and adults. Here, we report the cohort study of schoolchildren. The aim of the schoolchildren cohort study is to grasp the current status of children’s health after the disaster, focusing on allergic diseases, neuropsychiatric disorders and so on as the main outcome measures. Here we introduce the methodology of our research and its progress, focusing on allergic diseases.

Anaphylaxis from ingestion of mites: Pancake anaphylaxis

Oral mite anaphylaxis is a new syndrome characterized by severe allergic symptoms occurring immediately after eating foods made with mite-contaminated wheat flour. This syndrome, which is more prevalent in tropical environments, is triggered more often by pancakes, and for that reason, it has been designated "the pancake syndrome." Because cooked foods are able to induce the symptoms, it has been suggested that thermoresistant allergens are involved in its pathogenesis. A variety of this syndrome can occur during physical exercise (dust mite ingestion-associated exercise-induced anaphylaxis).

Old questions and novel clues: Complexity of IgE repertoires

Old questions and novel clues: Complexity of IgE repertoires

The complexity of allergic patients' IgE repertoire correlates with serum concentration of allergen-specific IgE

The governing factor of both effector-cell activation and facilitated antigen presentation is IgE-repertoire complexity (IgE-clonality, -affinity and -concentration). Yet, the compositions of individual IgE repertoires and correlation between IgE-repertoire complexity and establishment of allergic sensitization remain to be determined. In complex formation assays with recombinant IgE, allergen and CD23(+) B cells, we assess the composition of serum IgE repertoires and examine the correlation between IgE-titre and IgE-repertoire complexity. The capacity of sera, from house dust mite-sensitized individuals, to mediate IgE-Der p 2-CD23 complex formation on CD23(+) B cells was measured. In parallel experiments, the effect of supplementing each serum with one or more Der p 2-specific monoclonal recombinant IgE antibodies on complex formation was determined. Only sera with the highest concentration of Der p 2-specific IgE resulted in complex formation without supplementary recombinant IgE. Intermediately titred sera supported complex formation to various degrees when supplemented with individual recombinant IgE. The degree of complex formation depended on the affinity and epitope specificity of the recombinant IgE. Complex formation by combining serum and recombinant IgEs could not be obtained with sera of relatively low titres of specific IgE. However, these sera had the capacity to dramatically enhance the low complex formation achieved with pairs of affinity-engineered recombinant IgEs. Serum IgE complexity can be indirectly assessed by combining sera with defined monoclonal IgEs in IgE-allergen-CD23 complex assays. The observed differences in epitope-coverage of Der p 2-specific serum-IgE in sera of different specific IgE titres indicate that increased IgE titres correlate with increased complexity of the IgE-repertoire. A detailed knowledge of the composition and complexity of allergen-specific IgE repertoires (and the relation to IgE titre), particularly in the early phase of sensitization, may be used to improve the prediction of the persistence and severity of allergic symptoms, as well as the progression of the Allergic March.

GSTT1 gene abnormality in minimal change nephrotic syndrome with elevated serum immunoglobulin E

Imbalance between T-helper 1 (Th1) and 2 (Th2) lymphocytes and effects of reactive oxygen species (ROS) upon glomerular capillary walls have been implicated in minimal change nephrotic syndrome (MCNS). By polymerase chain reaction and comparative genomic hybridization, we evaluated mutations of the GSTT1 gene (GSTT1), a member of the glutathione S-transferase (GST) supergene family associated with both protection of cells from ROS and control of allergic reactions and serum immunoglobulin (Ig) E. Among 15 children with MCNS, IgE elevation (over 2,000 IU/l) and GSTT1 deletion was found in 2 who showed severe allergic symptoms. Serum ROS concentrations in these 2 patients were significantly higher than in healthy controls or other MCNS patients. In addition, a Th2 shift caused by increased serum interleukin (IL)- 4 was observed. These results suggest presence of a GSTT1 abnormality in some children with MCNS having marked serum IgE elevations and various allergic complications. Defective ROS degradation and Th1/Th2 imbalance caused by GSTT1 abnormality could initiate proteinuria leading to MCNS.

Involvement of Protein Kinase Cδ/Extracellular Signal-regulated Kinase/Poly(ADP-ribose) Polymerase-1 (PARP-1) Signaling Pathway in Histamine-induced Up-regulation of Histamine H1 Receptor Gene Expression in HeLa Cells

The histamine H(1) receptor (H1R) gene is up-regulated in patients with allergic rhinitis. However, the mechanism and reason underlying this up-regulation are still unknown. Recently, we reported that the H1R expression level is strongly correlated with the severity of allergic symptoms. Therefore, understanding the mechanism of this up-regulation will help to develop new anti-allergic drugs targeted for H1R gene expression. Here we studied the molecular mechanism of H1R up-regulation in HeLa cells that express H1R endogenously in response to histamine and phorbol 12-myristate 13-acetate (PMA). In HeLa cells, histamine stimulation caused up-regulation of H1R gene expression. Rottlerin, a PKCδ-selective inhibitor, inhibited up-regulation of H1R gene expression, but Go6976, an inhibitor of Ca(2+)-dependent PKCs, did not. Histamine or PMA stimulation resulted in PKCδ phosphorylation at Tyr(311) and Thr(505). Activation of PKCδ by H(2)O(2) resulted in H1R mRNA up-regulation. Overexpression of PKCδ enhanced up-regulation of H1R gene expression, and knockdown of the PKCδ gene suppressed this up-regulation. Histamine or PMA caused translocation PKCδ from the cytosol to the Golgi. U0126, an MEK inhibitor, and DPQ, a poly(ADP-ribose) polymerase-1 inhibitor, suppressed PMA-induced up-regulation of H1R gene expression. These results were confirmed by a luciferase assay using the H1R promoter. Phosphorylation of ERK and Raf-1 in response to PMA was also observed. However, real-time PCR analysis showed no inhibition of H1R mRNA up-regulation by a Raf-1 inhibitor. These results suggest the involvement of the PKCδ/ERK/poly(ADP-ribose) polymerase-1 signaling pathway in histamine- or PMA-induced up-regulation of H1R gene expression in HeLa cells.

Tomato hypersensitivity in peach allergic patients: rPru p3 and rPru p1 positivity is predictive of the symptom severity

Background allergy to tomato is very common in the Mediterranean area, where tomato consumption has increased in the last years: fresh in salads, cooked in household sauces or industrially processed foods. Many patients allergic to tomato present severe reactions and have symptoms also with commercial tomato products. Objective to examine the possibility of a relationship between severe allergic symptoms to tomatoes and peach; and, in the event of such a relationship, examine the correlation between severe tomato allergy and IgE positivity to peach allergens, i.e. Pru p 3 and Pru p 1. Methods within a population of patients with different grades of OAS for peach (mild-OAS, group A; and severe systemic symptoms to peach, group B) we selected patients with documented allergic reactions to tomato. We investigated the type of reaction to tomato by means of a clinical questionnaire, skin prick tests, prick + prick with fresh tomato and anti-rPru p 1, 3, 4, anti-rBet v 1, 2 and 4 IgE specific measurements. We compared the kind of clinical reactions to tomato between group A and group B patients. Statistical analyses were carried out with parametric and non parametric tests to examine the relationship between anti-rPru p 1 and 3 IgE levels and symptom severity. Results

Severe allergic symptoms to peach are a risk factor for severe symptoms to other plant food allergens

Objective A group of 148 peach allergic patients, recruited in a ongoing clinical study (Clinical Trials.gov, protocol ID NCT00715156) aimed at studying the relationship between the clinical manifestations to peach and the positivity to different peach major allergens (Pru p 3, 1 and 4), were divided into 2 groups according to peach induced symptoms: group A (mild-OAS; 76 pts) and group B (severe-OAS with systemic symptoms, 72 pts). These patients were examined to see if severe allergic symptoms to peach were a risk factor for developing severe symptoms to other plant foods allergens.

Effects of Topical Application of Ibudilast for Seasonal Allergic Conjunctivitis in Patients Wearing Soft Contact Lenses

To assess the influence of topical application of ibudilast for seasonal allergic conjunctivitis in patients wearing soft contact lenses (SCLs). There were 16 SCL wearers (32 eyes) with allergic conjunctivitis due to cedar pollen, who were studied from February to April 2007. Before enrollment, informed consent to participation in this study was obtained from all subjects. A frequent replacement SCL (2 Week Pure) was worn for 2 weeks, and ibudilast was applied topically four times daily during this period. The severity of allergic symptoms and the severity of SCL-related symptoms were assessed by scoring using two questionnaires, and before and after topical application of ibudilast results were compared. The severity of objective ocular findings was also scored and compared in the same way. After the final examination, the SCLs were collected and immersed in physiologic saline. Then morphologic changes and drug adsorption were investigated. Among the allergic symptoms, itching and a dry sensation improved after topical application of ibudilast ophthalmic solution (both P<0.05). Phlyctenular conjunctivitis was noted in one eye after topical application, but there were no significant differences of SCL-related symptoms and objective ocular findings between before and after application. There were also no morphologic changes of the contact lenses, and the ibudilast concentration in the lenses was below the detection limit. These results suggest that topical application of ibudilast while using 2 Week Pure lenses can improve subjective symptoms without influencing drug adsorption or lens morphology.

Allergic rhinitis in laboratory animal workers and its risk factors

The workers in an animal laboratory are exposed to laboratory animal allergens (LAAs). To evaluate the difference of sensitization to LAAs and the symptoms according to the exposure levels and to investigate the risk factors for sensitization to LAAs. The subjects were divided into 3 groups according to the presence or absence of exposure: 74 subjects were in the direct exposure group, 33 subjects were in the indirect exposure group, and 30 subjects were in the control group. Each group answered the questionnaire and underwent skin prick tests that included 10 common allergens and 10 LAAs. The levels of total IgE and specific IgE to mouse and rat urine allergen were measured by enzyme-linked immunosorbent assay in 2 exposure groups. Allergic symptoms, skin sensitization, and serum IgE level were compared between the study groups. Twenty-five (34%) of the 74 subjects in the direct exposure group experienced allergic symptoms since their exposure to laboratory animals. The subjects in the direct and indirect exposure groups had more sensitization to LAAs than did the control subjects. The direct exposure group had more positive results for total IgE than did the indirect exposure group. The subjects in the direct exposure group with atopy had more severe allergic symptoms than the subjects in the indirect exposure group with atopy. Atopy and total IgE level were risk factors for the sensitization to LAAs for the direct exposure group (odds ratios, 7.47 and 7.33, respectively). Indirect exposure may be as risky for sensitization to LAAs as direct exposure. More careful protection is needed for laboratory animal workers with atopy.

Regulatory Role of Lymphoid Chemokine CCL19 and CCL21 in the Control of Allergic Rhinitis

The lymphoid chemokines CCL19 and CCL21 are known to be crucial both for lymphoid cell trafficking and for the structural organization of lymphoid tissues such as nasopharynx-associated lymphoid tissue (NALT). However, their role in allergic responses remains unclear, and so our current study aims to shed light on the role of CCL19/CCL21 in the development of allergic rhinitis. After nasal challenge with OVA, OVA-sensitized plt (paucity of lymph node T cells) mice, which are deficient in CCL19/CCL21, showed more severe allergic symptoms than did identically treated wild-type mice. OVA-specific IgE production, eosinophil infiltration, and Th2 responses were enhanced in the upper airway of plt mice. Moreover, in plt mice, the number of CD4(+)CD25(+) regulatory T cells declined in the secondary lymphoid tissues, whereas the number of Th2-inducer-type CD8alpha(-)CD11b(+) myeloid dendritic cells (m-DCs) increased in cervical lymph nodes and NALT. Nasal administration of the plasmid-encoding DNA of CCL19 resulted in the reduction of m-DCs in the secondary lymphoid tissues and the suppression of allergic responses in plt mice. These results suggest that CCL19/CCL21 act as regulatory chemokines for the control of airway allergic disease and so may offer a new strategy for the control of allergic disease.