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A 20-year-old woman with a proven allergy to camomile suffered from short-lasting rhinitis when using a camomile-scented toilet paper. The prick-by-prick test performed with the toilet paper was positive. Diagnosis was confirmed by a challenge test that also resulted positive. This is the first reported case of toilet-paper-induced acute rhinitis. The removal of the toilet paper from the bathroom was sufficient to obtain the disappearance of symptoms. Patients allergic to camomile should avoid a camomile-scented toilet paper. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Long-term birth cohort studies are essential to understanding the life course and childhood predictors of allergy and the complex interplay between genes and the environment (including lifestyle and socioeconomic determinants). Over 100 cohorts focusing on asthma and allergy have been initiated in the world over the past 30 years. Since 2004, several research initiatives funded under the EU Framework Program for Research and Technological Development FP6-FP7 have attempted to identify, compare, and evaluate pooling data from existing European birth cohorts (GA2LEN: Global Allergy and European Network, FP6; ENRIECO: Environmental Health Risks in European Birth Cohorts, FP7; CHICOS: Developing a Child Cohort Research Strategy for Europe, FP7; MeDALL: Mechanisms of the Development of ALLergy, FP7). However, there is a general lack of knowledge about these initiatives and their potentials. The aim of this paper is to review current and past EU-funded projects in order to make a summary of their goals and achievements and to suggest future research needs of these European birth cohort networks. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Concepts of disease severity, activity, control and responsiveness to treatment are linked but different. Severity refers to the loss of function of the organs induced by the disease process or to the occurrence of severe acute exacerbations. Severity may vary over time and needs regular follow-up. Control is the degree to which therapy goals are currently met. These concepts have evolved over time for asthma in guidelines, task forces or consensus meetings. The aim of this paper is to generalize the approach of the uniform definition of severe asthma presented to WHO for chronic allergic and associated diseases (rhinitis, chronic rhinosinusitis, chronic urticaria and atopic dermatitis) in order to have a uniform definition of severity, control and risk, usable in most situations. It is based on the appropriate diagnosis, availability and accessibility of treatments, treatment responsiveness and associated factors such as comorbidities and risk factors. This uniform definition will allow a better definition of the phenotypes of severe allergic (and related) diseases for clinical practice, research (including epidemiology), public health purposes, education and the discovery of novel therapies. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Examines the immunological properties of Antigen (Ag) 5 allergens by preparing hybrids containing different segments of these two vespid Ag allergens. Way in which the structure of Vespula vulgaris 5 was solved; Details of the preparation and characterization of hybrid Ag 5 allergens; Antigenicity of hybrids in mice.

Background: Venom sac extract of yellow jackets Vespula vulgaris was toxic in mice when injected intraperitoneally but not toxic when injected subcutaneously. Necropsy showed the toxicity to be an inflammatory response. Methods: Venom peptide and protein fractions were tested to identify the inflammatory components. The active components were tested to establish whether they might function as adjuvant for venom protein-specific antibody response. Results: Venom toxicity required the synergistic action of two venom components, a mast cell degranulating peptide mastoparan and phospholipase A1. Both components stimulated prostaglandin E[sub 2] release from murine peritoneal cells and macrophages. Mastoparan showed a weak activity to enhance IgE and IgG1 responses to a yellow jacket venom protein Ves v 5 in BALB/c mice. It was not possible to assess the adjuvant activity of phospholipase A1 because of its suppression of Ves v 5-specific response. Melittin, a mast cell degranulating peptide from bee venom, was inactive as an adjuvant for Ves v 5-specific response. Conclusion: Yellow jacket venom contains two inflammatory components, mastoparan and phospholipase A1. Our findings suggest that mastoparan can function as a weak adjuvant for TH2 cell-associated antibody response.Copyright © 2003 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Anaphylaxis represents the most severe end of the spectrum of allergic reactions. Frequent elicitors of anaphylaxis are insects, foods, and drugs. This paper summarizes recent development with regard to emerging and novel elicitors of anaphylaxis. Summary: Food allergens on the rise include pulses (like pea, chickpea), seeds (hemp, chia), nuts (cashew), pseudograins (buckwheat, quinoa), fruits, and microalgae. Novel foods are foods that were not consumed to any significant extent in the European Union before May 1997, which includes four edible insects (mealworm, migratory locust, house cricket, and buffalo worm). Recent investigations have pointed out the risk of anaphylaxis associated with the consumption of yellow mealworm for people allergic to shellfish and house dust mites. In Europe, fire ants (mostly Solenopsis invicta) and Vespa velutina nigrithorax represent invasive species, which account for increasing numbers of anaphylactic reactions. Also, several new drugs, especially biologicals, have been associated with anaphylaxis. Key Messages: Elicitors of anaphylaxis are changing as a result of (i) increase in demand for plant-based food, (ii) introduction of novel foods, (iii) spreading of allergens by climate changes and globalization, or (iv) due to exposure to newly developed drugs. [ABSTRACT FROM AUTHOR]

Background: Compared to penicillin, cephalosporin allergies are less common in children, and their diagnostic approach is less standardized. A recent European Academy of Allergy and Clinical Immunology position paper provided a risk stratification system for patients with suspected β-lactam hypersensitivity reactions. Objective: This study aimed to evaluate risk stratification and predicting factors for confirmed cephalosporin hypersensitivity. Methods: The case-controlled study included patients with confirmed cephalosporin hypersensitivity (skin tests, n = 53; drug provocation, n = 19). For each patient, 2 age- and gender-matched control subjects were included in the study. Data were retrieved from patients' records and analyzed retrospectively. Risk stratification was performed according to the severity of index reactions, which was initially divided as high and low risk and then further divided as immediate and nonimmediate. Results: According to risk stratification, the patient and control groups were divided as follows: high-risk immediate (66.7% vs. 13%, respectively), high-risk delayed (1.4% vs. 8.3%, respectively), low-risk immediate (16.7% vs. 16%, respectively), and low-risk delayed (15.3% vs. 62.9%, respectively). Immediate reactions (odds ratio [OR]: 12.1, 95% confidence interval [CI]: 9–24.8, p < 0.001) and high-risk reactions (OR: 7.8, 95% CI: 4.1–14.6, p < 0.001) were associated with confirmed cephalosporin hypersensitivity in univariate analysis. Multivariate regression analysis indicated that immediate reactions (OR: 7.5, 95% CI: 3.3–16.8, p < 0.001) and high-risk reactions (OR: 5.2, 95% CI: 2.1–12.9, p < 0.001) were significant risk factors for the prediction of cephalosporin hypersensitivity. Conclusion: This model can be applied in children with suspected cephalosporin allergy. Skin testing provides diagnostic information in high-risk patients with immediate reactions and reduces the need for drug provocation testing in these patients. It is highly likely to confirm the diagnosis of low-risk patients directly with provocation tests without skin tests. High-risk and immediate reactions were found to be predictive factors for confirmed cephalosporin allergy. [ABSTRACT FROM AUTHOR]

Introduction: circRNA played a role in a variety of diseases. This paper aimed to explore the differentially expressed circRNA in induced sputum cells of asthma patients, so as to provide new potential biomarkers and new ideas for the study of asthma. Methods: All subjects were from the First Affiliated Hospital of Sun Yat-sen University. Differentially expressed circRNAs of asthma patients were screened by high-throughput sequencing. qRT-PCR was used to verify the expression of differential circRNAs. The association between circRNA and asthma was explored by analyzing the correlation between circRNA and clinical data and some cytokines of asthma patients. The possible ceRNA network was analyzed and predicted by online software, and the expression of each molecule in the network was preliminary verified by qRT-PCR in induced sputum cells and 16HBE cell. Results: We screened a total of 49 circRNAs differentially expressed in asthma patients (including 12 circRNAs with elevated expression and 37 circRNAs with decreased expression), among which has_circSORT1 and has_circSERPINB1 were significantly elevated. Correlation analysis showed that has_circSORT1 was correlated with FeNO, EOS%, IL-17A, IFN-γ, and PC20, and has_circSERPINB1 was correlated with IL-6, IL-17A, IFN-γ, FEV1%, and FVC%. The possible existence of has_circSORT1/has-miR-185-3p/ZNFX1, a ceRNA regulatory network, in induced sputum cells of asthma patients was hypothesized by online software prediction and qRT-PCR in sputum cells and 16HBE. Conclusion: Differentially expressed circRNAs existed in induced sputum cells of asthma patients, among which has_circSORT1 and has_circSERPINB1 were significantly upregulated and may be involved in the process of asthma disease, which could be expected to be a potential biomarker for asthma diagnosis. In addition, a ceRNA regulatory network, has_circSORT1/has-miR-185-3p/ZNFX1, may exist in asthma. [ABSTRACT FROM AUTHOR]

Introduction: Allergen-specific IgE (sIgE) sensitization exists in a considerable fraction of chronic spontaneous urticaria (CSU) patients. Basophils have been implicated in the pathogenesis of CSU. This paper aimed to explore the relationship between allergic sensitization and basophil reactivity in CSU and the possible underlying mechanism. Methods: Basophil-enriched leukocytes were isolated from the peripheral blood of 76 CSU patients and 9 healthy controls. Basophil CD63 and FcεRIα (the alpha subunit of the high-affinity IgE receptor) expression in the blood samples with various house dust mite (HDM)-sIgE levels were determined by flow cytometry. Basophil reactivity and SHIP-1 (a molecule related to the IgE/FcεRI signaling pathway) expression were analyzed after stimulation with an HDM allergen or other stimuli. Results: HDM-sIgEstrong positive (≥3.5 kU/L) CSU patients had a significantly higher mean percentage of basophil CD63 and higher baseline levels of FcεRIα expressed by basophils than HDM-sIgEnormal (<0.35 kU/L) CSU patients and healthy controls; the same went for total serum IgE. After stimulation with Dermatophagoides pteronyssinus peptidase 1 (Derp1) alone or together with Derp1-sIgE, the stimulation index of CD63 and levels of FcεRIα expressed by basophils in HDM-sIgEstrong positive CSU patients were significantly higher than those in HDM-sIgEnormal CSU patients and healthy controls. Significantly more SHIP-1 mRNA expression in HDM-sIgEstrong positive CSU patients was induced after the combined stimulation in comparison to other subjects. Conclusion: CSU patients with higher HDM-sIgE levels (≥3.5 kU/L) may have higher CD63 and FcεRIα expression on peripheral blood basophils. Peripheral blood basophils in these CSU patients are more responsive to HDM allergen stimulation. Higher HDM-sIgE levels among CSU patients may implicate higher basophil reactivity. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to identify the histopathologic characteristics associated with difficult-to-treat chronic rhinosinusitis with nasal polyps (CRSwNPs), enabling physicians to predict the risk of poor outcome after endoscopic sinus surgery (ESS). Methods: A prospective cohort study performed at the First Affiliated Hospital of Sun Yat-sen University between January 2015 and December 2018 with CRSwNP patients who underwent ESS. Polyp specimens were collected during surgery and were subjected to structured histopathological evaluation. Difficult-to-treat CRSwNPs were determined at 12–15 months post-operation according to the European Position Paper. Multiple logistic regression model was used to assess the association between histopathological parameters and the difficult-to-treat CRSwNP. Results: Among 174 subjects included in the analysis, 49 (28.2%) were classified with difficult-to-treat CRSwNP, which had higher numbers of total inflammatory cells, tissue eosinophils, and percentages of eosinophil aggregates and Charcot-Leyden crystals (CLC) formation but a lower number of interstitial glands than the nondifficult-to-treat CRSwNP. Inflammatory cell infiltration (adjusted OR: 1.017), tissue eosinophilia (adjusted OR: 1.005), eosinophil aggregation (adjusted OR: 3.536), and CLC formation (adjusted OR: 6.972) were independently associated with the difficult-to-treat outcome. Furthermore, patients with tissue eosinophil aggregation and CLC formation had an increasingly higher likelihood of uncontrolled disease versus those with tissue eosinophilia. Conclusion: The difficult-to-treat CRSwNP appears to be characterized by increased total inflammatory infiltrates, tissue eosinophilia, eosinophil aggregation, and CLC formation in structured histopathology. [ABSTRACT FROM AUTHOR]

Introduction: Several statements and position papers on the management of childhood asthma and allergies during the COVID-19 pandemic have been published of late. The aim of this study was to evaluate the knowledge and awareness of pediatricians and family physicians regarding the management of asthma and allergic rhinitis during the pandemic according to recently published updated guidelines. Method: We conducted an online survey among pediatricians and family physicians in Turkey, using a questionnaire designed to evaluate 4 items: (1) the relationship between COVID-19 infection risk and pediatric asthma/allergic rhinitis and medications used in treatment; (2) the follow-up and management of asthma/allergic rhinitis according to published updated recommendations; (3) pediatricians' and family physicians' observations and perceptions of treatment compliance and the attitudes of their pediatric asthma patients; and (4) pediatricians and family physicians' attitudes to using telehealth in the follow-up and management of pediatric asthma patients during the pandemic. Results: A total of 346 participants responded to the survey. The relationship between the risk of COVID-19 and asthma was known by less than 25% of the participants. More than 33% of family physicians and 20% of pediatricians were unaware that asthma medication does not lead to a susceptibility to COVID-19 infection; 55% of family physicians and 48% of pediatricians thought that patients showed better compliance with asthma controller medication; over 33% of pediatricians and approximately 50% of family physicians stated that they could not distinguish between an asthma attack and lung involvement in COVID-19 infection; of the respondents, over 75% stated that they prefer face-to-face visits with patients, even in situations that do not require a physical examination. Conclusion: The overall knowledge and awareness of pediatricians and, especially, family physicians regarding the management of pediatric asthma/allergic rhinitis during the pandemic is not at a satisfactory level. There is an urgent need to inform them about updated recommendations appearing in recent guidelines published by allergy organizations. [ABSTRACT FROM AUTHOR]

Introduction: Chemotherapy drugs have been in our lives for a long time, and all agents have the potential to develop hypersensitivity. Rapid drug desensitization is an option when hypersensitivity develops. The aim of this study was to examine the characteristics, diagnostic processes, and treatment results of patients with chemotherapeutic agent hypersensitivity who applied to our tertiary reference center. Methods: Patients who applied to our tertiary allergy outpatient clinic between January 2016 and September 2022 due to chemotherapy-induced drug hypersensitivity were examined. Demographic data of the patients, cancer diagnoses, chemotherapy regimens, skin tests, premedication scheme, desensitization cycle were evaluated. We applied a 16-step desensitization in patients with index reaction anaphylaxis or positive skin tests. If the index reaction was not anaphylaxis or skin tests were negative, we applied a 12-step desensitization. If the prick test with chemotherapeutic drugs was negative especially with taxanes, premedication was administered. We used the montelukast, cetirizine, and methylprednisolone for premedication. Results: Fifty-one patients were evaluated; 35 (68.6%) were female. The most common malignancy was colorectal cancer in 17 (33.3%) patients. The most common agent responsible for hypersensitivity was oxaliplatin in 17 (33.3%) patients, followed by paclitaxel in 13 (25.4%). When the symptoms of immediate reaction to chemotherapeutic drugs were analyzed as described in the EAACI position paper, only skin and mucosal involvement was seen in 24 (46.8%) patients; only respiratory system involvement or back pain was seen in 3 (6.2%) patients; multisystem involvement meeting the criteria for anaphylaxis was seen in 24 (47%) patients. Skin test was positive in 17 (56.6%) of 30 patients who developed a reaction with platin. Prolonged anaphylaxis was developed in 1 patient, and desensitization was not performed again. Fifty of 51 patients were able to receive the target chemotherapy dose by desensitization. In total, a 172-step desensitization was applied to 51 patients. Conclusion: If completing the cycle is considered a treatment success, this was achieved in 98% (50/51) patients with rapid drug desensitization. This gives us the opportunity to use first-line chemotherapy agents. [ABSTRACT FROM AUTHOR]

Coronaviruses (CoVs) were first discovered in the 1960s. Severe acute respiratory syndrome CoV-2 (SARS-CoV-2) has been identified as the cause of COVID-19, which spread throughout China and subsequently, across the world. As COVID-19 causes serious public health concerns across the world, investigating the characteristics of SARS-CoV-2 and its interaction with the host immune responses may provide a clearer picture of how the pathogen causes disease in some individuals. Interestingly, SARS-CoV-2 has 80% sequence homology with SARS-CoV-1 and 96–98% homology with CoVs isolated from bats. Therefore, the experience acquired in SARS and Middle East Respiratory Syndrome (MERS) epidemics may improve our understanding of the immune response and immunopathological changes in COVID-19 patients. In the present paper, we have reviewed the immune responses (including the innate and adaptive immunities) to SARS-CoV, MERS-CoV, and SARS-CoV-2, so as to improve our understanding of the concept of the COVID-19 disease, which will be helpful in developing vaccines and medications for treating the COVID-19 patients. [ABSTRACT FROM AUTHOR]

As an ancient Gram-negative bacterium, Helicobacter pylori has settled in human stomach. Eradicating H. pylori increases the morbidities of asthma and other allergic diseases. Therefore, H. pylori might play a protective role against asthma. The "disappearing microbiota" hypothesis suggests that the absence of certain types of the ancestral microbiota could change the development of immunology, metabolism, and cognitive ability in our early life, contributing to the development of some diseases. And the Hygiene Hypothesis links early environmental and microbial exposure to the prevalence of atopic allergies and asthma. Exposure to the environment and microbes can influence the growing immune system and protect subsequent immune-mediated diseases. H. pylori can inhibit allergic asthma by regulating the ratio of helper T cells 1/2 (Th1/Th2), Th17/regulatory T cells (Tregs), etc. H. pylori can also target dendritic cells to promote immune tolerance and enhance the protective effect on allergic asthma, and this effect relies on highly suppressed Tregs. The remote regulation of lung immune function by H. pylori is consistent with the gut-lung axis theory. Perhaps, H. pylori also protects against asthma by altering levels of stomach hormones, affecting the autonomic nervous system and lowering the expression of heat shock protein 70. Therapeutic products from H. pylori may be used to prevent and treat asthma. This paper reviews the possible protective influence of H. pylori on allergic asthma and the possible application of H. pylori in treating asthma. [ABSTRACT FROM AUTHOR]

Background: Mean diameter or longest diameter are the 2 most frequently used parameters for wheal response assessment after skin prick testing (SPT). We aimed to compare these 2 parameters taking as gold standard the surface of the wheal skin response. Patients and Methods: Patients suspected of having an allergic reaction against inhalant allergens have been skin prick tested using the Pan-European GA2LEN SPT panel. Fifteen minutes later, macroscopically evident wheal and flare reactions were marked with a pen and transferred to paper with a transparent scotch tape. Each paper-transferred wheal was scanned with an ordinary scanner, and its surface-corresponding maximum perpendicular diameters and longest diameters were measured using a computer software application for image recognition, developed for this purpose. Correlation coefficients (Spearman’s ρ) between surfaces and respective mean (ρmean) or longest (ρlongest) diameters were calculated and subsequently compared. Results: 1,554 SPTs were performed in 74 patients. In 264, a macroscopically evident wheal and flare response was observed. Both mean and longest diameters correlated significantly with the wheal surfaces. However, ρlongest was statistically significantly larger than ρmean when the surface of the wheal was >17 mm2 (ρlongest > 0.860 vs. ρmean < 0.660; p < 0.05).Such a surface corresponds to a maximum diameter of approximately 7 mm and a mean diameter of approximately 6 mm. Thus, the larger the surface of the wheal, the more appropriate the usage of the longest diameter. Conclusions: The longest wheal diameter alone seems to be a better surrogate marker of the wheal surface in comparison with the mean diameter. In addition, it is easier and faster to measure. Therefore, we propose this as the optimal methodology to evaluate SPTs. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Insect venom allergy is common and greatly impairs patients’ quality of life. Additionally, low compliance with carrying emergency medication is reported. The aim of our study was to analyze the disease burden, levels of anxiety and depression, and to evaluate attitudes towards the set of emergency medication in affected patients. Methods: Between April 2016 and January 2017, patients ≥18 years visiting our department because of an insect venom allergy were asked to complete a paper-based questionnaire. The questionnaire assessed willingness to pay (WTP), the Hospital Anxiety and Depression Scale (HADS), subjective anxiety levels, willingness to carry the set of emergency medication, self-assurance in using it, compliance with carrying it, and reasons for not always carrying it. Results: 55 patients (81.8% wasp allergy) were included. On average, WTP for a complete cure was EUR 1,727 (median: 500). Using the HADS, 14.5% showed definite anxiety disorders while 5.5% had significant depression disorders. Most patients stated to carry the emergency medication “always” (25.5%) or “almost always” (47.3%). “Forgetfulness” (36.4%) was reported as the main reason for not always carrying the medication, followed by “too big” (18.2%). Conclusions: In our patient cohort, insect venom allergy was associated with a moderate disease burden and a good compliance with carrying the emergency medication. However, several of our participants demonstrated borderline or significant anxiety and/or depression disorders. In this regard, this study highlights the necessity to regularly ask the patient about the psychological well-being to identify patients needing psychological support. [ABSTRACT FROM AUTHOR]

This paper proposes that reduced allergen exposure is one of the factors underlying the higher risk of IgE-mediated allergic disease in populations with an urbanized, westernized, and affluent lifestyle. This lower allergen exposure results in the failure to induce and maintain immune tolerance to common environmental allergens. The paper summarizes different lines of evidence that may support or contradict this hypothesis and points to areas where more knowledge is needed. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Over the last 20 years, diverse outcome measures have been used to evaluate the effectiveness of therapies for eosinophilic esophagitis (EoE). This systematic review aims to identify the readouts used in observational studies of topical corticosteroids, diet, and dilation in adult EoE patients. Methods: We searched MEDLINE and Embase for prospective and retrospective studies (cohorts/case series, randomized open-label, and case-control) evaluating the use of diets, dilation, and topical corticosteroids in adults with EoE. Two authors independently assessed the articles and extracted information about histologic, endoscopic, and patient-reported outcomes and tools used to assess treatment effects. Results: We included 69 studies that met inclusion criteria. EoE-associated endoscopic findings (assessed either as absence/presence or using Endoscopic Reference Score) were evaluated in 24/35, 11/17, and 9/17 studies of topical corticosteroids, diet, and dilation, respectively. Esophageal eosinophil density was recorded in 32/35, 17/17, and 11/17 studies of topical corticosteroids, diet, and dilation, respectively. Patient-reported outcomes were not uniformly used (only in 14, 8, and 3 studies of topical corticosteroids, diet, and dilation, respectively), and most tools were not validated for use in adults with EoE. Conclusions: Despite the lack of an agreed set of core outcomes that should be recorded and reported in studies in adult EoE patients, endoscopic EoE-associated findings and esophageal eosinophil density are commonly used to assess disease activity in observational studies. Standardization of outcomes and data supporting the use of outcomes are needed to facilitate interpretation of evidence, its synthesis, and comparisons of interventions in meta-analyses of therapeutic trials in adults with EoE. [ABSTRACT FROM AUTHOR]

Background: Specific immunotherapy (SIT) is a well-documented treatment for respiratory allergy. However, the major risk of SIT is the development of systemic anaphylactic reactions. Objectives: To evaluate the safety of SIT given by subcutaneous route for 3 years to patients with seasonal allergic rhinitis (AR) with or without asthma. Methods: A prospective open-label study of immunotherapy (Chenopodium album, Bermuda grass, or both) in 181 consecutive patients with AR with or without asthma. After an initial dose-escalation phase, a maintenance dose of 0.5 ml of 100,000 PNU/ml was administered monthly for 3 years. The occurrence and severity of systemic reaction (SR) and local reaction was recorded and graded according to the WHO position paper. Results: Of 181 patients enrolled, 57 (31%) did not complete the study (53 due to poor compliance and 4 due to systemic side effects). All 4 patients who developed SR had asthma and all the SR occurred during the dose- escalation phase. Three patients had moderate SR (grade 2), while 1 patient had severe reaction (grade 3). Three of the SR occurred within the first 20 min after injection and 1 SR occurred 2 h after injection. None of the reactions were life threatening and were managed easily. Total rhinitis symptom score decreased from 11.8 at baseline to 7.46 at the end of treatment (p < 0.001). The size of the skin prick test reaction to the main sensitising allergen was reduced from 7.48 ± 2.26 mm at baseline to 5.60 ± 2.18 mm at the end of treatment, p < 001. Conclusion: If a strict protocol is used, SIT is safe in AR patients with or without mild asthma and may result in significant subjective and objective improvement.Copyright © 2003 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Bovine serum albumin (BSA) is one of the most widely studied proteins; its structure is well known and its antigenic characteristics have been described in several papers. The aim of this research was the identification of the BSA antigenic determinants. Methods: This study was performed using limited proteolysis and an immunoblotting technique, in which a commercial murine antibody and sera from children sensitized to BSA were used. Results: Findings suggest amino acids (aa) 524–598 as an epitopic area for human species. The most critical sequence seems to be aa 524–542, even if it must be included in a longer fragment to be recognized by antibodies. Murine IgG antibodies also recognize fragments contained in the first half (NH[sub 2] -terminal portion) of BSA. Conclusions: The results presented in this study indicate that the epitopic sites of an antigenic protein can be different when different species are considered, so that data obtained with antibodies from animal species cannot be directly extrapolated to the behavior of human IgEs.Copyright © 2001 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Bees, fire ants and vespids cause insect sting allergy. These insects have unique as well as common venom allergens. Vespids, including hornets, paper wasps and yellow jackets, have common allergens. Bees and vespids have one common allergen with hyaluronidase activity; they also have unique allergens with different phospholipase activities. Fire ants and vespids have one common allergen, antigen 5 of unknown biologic activity. The common venom allergens with < 70% sequence identity have barely detectable levels of antigenic cross-reactivity. Possible uses of modified allergens for immunotherapy are described.Copyright © 2000 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Immunotherapy is an established treatment of allergic diseases. The safety of this treatment, particularly when administered without direct medical surveillance, as in the case of the sublingual-swallow route needs to be established. The aim of this paper is to review the safety of the sublingual-swallow immunotherapy as reported in eight double-blind, placebo-controlled trials carried out in France, Italy and Greece. Methods: Six hundred and ninety subjects, 472 adults and 218 children, took part in trials of specific immunotherapy (SIT) for the treatment of rhinoconjunctivitis and/or asthma. Three hundred and forty-seven patients received SIT and 343 patients received placebo. Treatment with specific immunotherapy with allergen extracts or placebo was administered using the sublingual-swallow technique. The allergens administered were grass, ambrosia, parietaria and olive pollens, and mites. The daily dose taken during maintenance therapy ranged from 100 to 300 IR (index of reactivity) and cumulative doses ranged from 4,500 to 104,000 IR. Treatment duration ranged from 4 months to 2 years. Adverse events reported either spontaneously by the patient or on direct questioning by the investigator were analysed. Results: One hundred and forty-five unusual events were reported in the subjects receiving active SIT and 79 in those receiving placebo (p < 0.001). Of these 85 were children aged 15 years or less (50 received active SIT, 35 placebo) and 139 were adults (95 received SIT, 44 placebo). Unusual events involving the buccal cavity (61 SIT, 13 placebo) and the gastro-intestinal tract (47 SIT, 15 placebo) were significantly more frequent in the SIT-treated patients (p < 0.001). Wheezing (9 SIT, 21 placebo) was more frequent in the placebo-treated patients (p < 0.05). There were no differences in the frequency of unusual events between adults and children and in the frequency of events involving other body systems. No event was reported as serious. Two events reported as laryngeal oedema were not considered to be accurate descriptions. Conclusions: No serious adverse event was reported in the studies monitored, confirming the good safety profile of the sublingual-swallow method both in children and adults with rhinitis or moderate asthma.Copyright © 2000 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Allergic reactions in patients with seasonal or perennial rhinoconjunctivitis mediated by airborne allergens can be effectively assessed with the conjunctival provocation test (CPT). The CPT is a fast and easy diagnostic procedure that challenges the ocular mucosa with instillations of allergen solutions into the conjunctival region. This paper aimed to investigate the possible influence of repeated diagnostic CPT procedures on the patient's clinical presentation, i.e. to analyze desensitization effects caused by diagnostic solutions and to show the reproducibility of CPT results. Methods: Treatment progress in 120 placebo-treated patients from 2 immunotherapeutic dose-finding studies was estimated and documented, as based on the CPT which was applied at 4 visits with intervals of 4,8 and 16 weeks. High-resolution digital photos collected as part of the CPT documentation were analyzed by an external observer and by digital analysis software to determine conjunctival redness, completely independent of the subjectivity of investigators and patients. Results: Two extremal scenarios of the redness changes were considered after provocation with 10,000 standard quality units/ml. A maximal decrease of about 3% (t test: p = 0.0002; U test: p = 0.001) and a minimal decrease of about 1 % (t test: p = 0.254; U test: p = 0.431) were found. Conclusions: The observed decrease in conjunctival hyperemia can be explained by local desensitization or by placebo effect. Due to the setup of both studies considered, we could not ascertain how these factors influence the decrease in redness. In order to attribute the observed effects to local conjunctival desensitization with certainty, further pilot studies are needed. [ABSTRACT FROM AUTHOR]

Pharmacotherapy is widely used to manage allergic rhinitis (AR), but often does not adequately control symptoms. Allergy immunotherapy (AIT) should be considered for patients who are not adequately controlled on symptomatic treatment. AIT is gaining attention because of its potential to improve symptom relief and quality of life, and to provide sustained effect after the end of treatment by modifying the course of disease. However, evidence of efficacy needs to be shown for each individual AIT product, based on state-of-the-art studies. The majority of products cannot truly claim efficacy and disease-modifying potential, as evidence of such an effect from robust randomized double-blind, placebo-controlled long-term trials is lacking. The potential of a specific immunotherapy product should be evaluated against four levels of benefit defined by the European Medicines Agency (EMA) guideline on clinical development of AIT products. These clearly distinguish between efficacy of symptom relief in the first year, efficacy over 2-3 treatment years, sustained efficacy and disease modification treatment ends, and sustained absence of allergic symptoms in posttreatment years. The clinician's choice of a specific AIT product should take the level of evidence and risk/benefit into account, as the patient's quality of life and the product's potential long-term effect are important components of its overall cost-effectiveness. Without evidence of maintained clinical benefit and disease modification after the end of treatment, claims of long-term economic benefit of specific AIT products cannot be justified. This paper discusses the evidence that is essential for critical evaluation of product claims in health economic analysis comparing AIT products. © 2016 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

A preface for the Volume 143, Supplement 1, 2007 of the journal "International Archive of Allergy and Immunology" is presented.

Background: Epicutaneous immunotherapy targets the network of dendritic cells in the epidermis. Allergen exposure of the dermal layers should be limited as these contain mast cells and blood vessels, which increases the risk for local and systemic allergic reactions. Methods: This intraindividually controlled trial included 20 subjects with birch pollen allergy. Three areas of the volar forearms were treated by repeated adhesive-tape stripping, single-prick lancet piercing and microneedle array application. Four 10-fold dilutions of allergen extract were applied to each area and the IgE-mediated immediate-phase reactions and cell-mediated eczema were assessed. Results: Allergen application after tape stripping led to an immediate-phase reaction in 2 subjects (10%) at the highest allergen concentration of 10 HEP/ml. Both prick needle and microneedle pretreatment resulted in immediate-phase reactions in all subjects (100%). The reactivity pattern, however, differed significantly: 95% of the reactions after pricking occurred at concentrations of ≤0.1 HEP/ml, whereas 50% of the reactions after microneedle preparation were noted at ≥1 HEP/ml. In 3 subjects (15%), eczema was observed on the microneedle-treated skin area. No serious adverse events occurred. Conclusions: Microneedles enhance stratum corneum penetration when compared to tape stripping. However, they do not resolve the problem of mast cell-mediated local reactions, possibly due to diffusion into the dermis. The occurrence of eczema after the microneedle treatment suggests induction of dendritic cell-mediated T cell responses. Therefore, skin preparation with microneedles may be a promising method for epicutaneous allergen immunotherapy. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: The allergen dose-response curve is flat; thus, small changes in wheal size reflect large differences in skin sensitivity. The sensitivity as measured by provocation tests is given by the threshold concentration that causes symptoms and/or objective signs. The threshold concentrations differ by several magnitudes between the most and the least sensitive individuals clinically allergic to the same allergen. Variation in technique can be minimized by relating allergen responses to that to histamine. The aim here is to present and validate simple methods for estimation of the skin sensitivity given as the concentration inducing a wheal of the same size as that with the positive reference, 10 mg/ml of histamine HCl, in the same patient. Methods: Data from previously reported trials on the biological equilibration of allergen extracts were used to document a method to calculate the concentration of allergen required to induce a wheal of the same size as that with 10 mg/ml of histamine dihydrochloride in the same patient, and to validate the methods using the parallel line bioassay as the gold standard. Results: The validated methods correlated well with the results obtained using the gold standard method and provide results of skin prick testing based on threshold concentrations of allergen. Conclusions: The validated methods reduce the error of differences in testing techniques and make it possible to report skin sensitivity at threshold concentrations. A simple method to be used in clinical practice and a method suitable to describe changes in skin reactivity over time or during treatment are proposed. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: This paper reports the case of an egg-allergic pediatric patient who, once desensitized to egg following a successful rush oral immunotherapy protocol, could also tolerate Lizipaina®, a drug containing lysozyme (LYS) and papain, which had previously caused him a severe allergic reaction. Because the LYS amount that elicited the anaphylactic reaction (5 mg) was much lower than that tolerated during a double-blind placebo-controlled food challenge (corresponding to approximately 60 mg of LYS), the possibility that the presence of papain could increase the allergenic potential of LYS was investigated. Methods: Lizipaina, LYS and LYS hydrolyzed with papain were analyzed by SDS-PAGE under reducing and nonreducing conditions, and Western blotting of sera from egg-allergic patients was performed in order to detect IgE-binding fragments. Finally, sequence identification of the IgE-reactive bands was carried out by MALDI-TOF/TOF. Results: The SDS-PAGE pattern of LYS treated with papain under nonreducing conditions showed the presence of intact LYS that partially disappeared following reduction with β-mercaptoethanol, releasing IgE-reactive fragments as determined by Western blotting. MALDI-TOF/TOF revealed that papain degraded LYS, giving rise to three IgE-binding fragments: LYS (22-129), LYS (34-96) and LYS (62-128) that likely remained linked through the disulfide bonds present in the LYS molecule. Conclusion: The combined administration of LYS with proteolytic enzymes such as papain may have developed a severe allergic reaction in the patient studied, underlining the importance of considering all the components and their interactions when drugs are to be consumed by allergic persons. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: In 2003, this laboratory published an account of the human mast cell line LAD2 (Laboratory of Allergic Diseases 2) that expressed FcεRI, responded to recombinant human stem cell factor (rhSCF) and resembled CD34+-derived human mast cells. LAD2 cells have now been distributed worldwide. To study the impact of this transfer, we analyzed the number of investigators receiving LAD2 cells and resulting publications. Methods: Records maintained in our laboratory, the Technology Transfer and Intellectual Property Office and Office of Technology Transfer, were reviewed for material transfer agreements (MTAs) and licensing agreements (LAs). Journals and impact factors were obtained from PubMed.gov by cross-referencing LAD2 and human mast cells from 2003 through November 2013. Results: Over 300 MTAs and 40 LAs were approved. LAD2 cells were shipped to over 30 countries. More than 80 papers have been published in journals with impact factors from 1.31 to 13.21. Intended uses include the study of receptors, degranulation, and cell signaling. LAD2 cells continue to express described markers and have consistent FcεR1-mediated degranulation. Conclusions: Success of the LAD2 line reflects the demand for a human mast cell line in research, the uniqueness of this cell line, and that it continues to exhibit minimal variation from its original description. We hope that the awareness of the impact of this cell line on mast cell research will encourage others to develop and distribute other similar cell lines with additional characteristics so as to address the limitations of depending on the study of cultured human mast cells from tissues. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

We wish to retract the paper entitled "BIOBRAD Study: The Search for Biomarkers of Bradykinin-Mediated Angio-Oedema Attacks" [Int Arch Allergy Immunol. 2016;170(2):108-14, DOI: 10.1159/000446959] by Deroux et al. At the beginning of the study, some procedural irregularities occurred during a quality approach, and this forces us, according to the French authority ANSM (Agence Nationale de Sécurité du Médicament et des Produits de Santé), to retract this article from the journal I International Archives of Allergy and Immunology i . According to the promotor of the study, data from these patients must not be used and published anymore. [Extracted from the article]

Background: Patients with allergic rhinoconjunctivitis are susceptible to both nasal and ocular symptoms. The conjunctival provocation test (CPT) is an established diagnostic procedure used in allergic rhinoconjunctivitis, particularly to document a patient's current reactivity to allergens. To date, there are no international guidelines defining the CPT. No approved evaluation method exists for interpreting CPT results. This paper aims to establish the digital analysis of macroimages as an objective, validated and standardized method for interpreting CPT results. Methods: In a clinical immunotherapy trial with 155 patients, treatment progress was documented based on the CPT. Local investigators used a symptom score to grade tearing, reddening and the patients' subjective perception of symptoms (mucosal irritation). A central observer rated conjunctival hyperemia via digital photography. Digital image analysis software was utilized to determine conjunctival hyperemia. Results: Spearman's correlation between the local investigators' and the central observer's ratings was r = 0.729 (p < 0.001); the percentage of total agreement was 48% (based on 739 photos). Digital image analysis (based on 48 photos) had a high percentage of total agreement with the central observer's ratings (69%) but a low percentage of total agreement with the investigators' ratings (38%). The corresponding correlations were r = 0.264 and 0.064, respectively. Conclusion: Photography-based rating by a central observer may represent a valuable supplement to the local investigator's assessment for making an objective evaluation of CPT results. Digital image analysis possesses the potential of being an objective evaluation method compared to the wide-spread subjective evaluation by the investigators. © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Because of changing world demographics, the elderly population is steadily increasing. Few studies have assessed the prevalence of atopy and allergic diseases in elderly persons with objective measures. The aim of this paper is to describe the prevalence of atopy, self-reported allergic rhinitis and doctor's diagnosed asthma in persons over the age of 60 in Switzerland. Methods: The cross-sectional examination of the Swiss Study on Air Pollution and Health in Adults (SAPALDIA 1), performed in 1991, included 9,651 adults aged 18-60 years. In 2001-2002 the same subjects were invited for a follow-up examination (SAPALDIA 2). Serum samples collected at baseline and follow-up were tested for specific IgE sensitization with the Phadiatop® (Phadia, Uppsala, Sweden, now Thermo Fisher Scientific) assay containing a mixture of common respiratory allergens (grass, birch, mugwort, Parietaria and olive pollen, dog, cat, horse, Cladosporium herbarum, house dust mite and flour mite). Atopy was defined as a positive result in the Phadiatop test according to guidelines by the manufacturer. The prevalence rates of atopy, self-reported allergic rhinitis and doctor's diagnosed asthma were evaluated by sex and age group (≤60 or >60 years). Results: 7,667 subjects (men = 3,692/women = 3,975) participated in the follow-up by responding to a detailed questionnaire (80% of SAPALDIA 1 participants). Phadiatop results were available for 5,835 participants (men = 2,839/women = 2,996). Prevalence rates of atopy (Phadiatop positive) were 36.4% in men aged ≤60 years versus 26.2% in men aged >60 years and 30.6 and 18.1% in women, respectively (both p < 0.001). Prevalence rates of self-reported allergic rhinitis in subjects >60 years old were 13.0% for men and 15.4% for women (p = 0.12), and for doctor's diagnosed asthma 6.6% versus 7.6%, respectively (p = 0.40). Both rhinitis and asthma prevalences were higher in persons <60 years. The results were not sensitive to potential bias from nonparticipation at follow-up as demonstrated by imputation of sex- and age-specific allergic rhinitis and asthma among nonparticipants. Conclusions: According to our estimates, the prevalence of allergic rhinitis among persons aged between 60 and 70 years in Switzerland in the present cohort is of the order of 13-15% and should not be underestimated, although it is lower than in age groups ≤60 years. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Although some authors have already evaluated the predictive value of various parameters regarding the duration of chronic spontaneous urticaria (CSU), it remains uncertain which ones have importance in clinical practice as prognostic factors that indeed enable prediction. Similarly, some authors have investigated parameters that might be related to severe cases of CSU. However, the results of studies evaluating several parameters as markers of disease severity are fragmented. Thus, we performed a systematic review to summarize the findings of studies investigating the parameters associated with CSU duration and severity. Methods: Two authors independently searched PubMed until June 2012 for observational retrospective or prospective studies addressing clinical or laboratory parameters associated with disease duration or severity in CSU patients. Results: We found 1,136 potentially relevant published papers related to the subject, 34 of which were included in the systematic review. A total of 16, 6 and 12 articles evaluated CSU parameters on severity, duration or both, respectively. Conclusions: Our findings suggest that disease severity might predict CSU duration. Similarly, evidence suggests that plasma levels of prothrombin fragment 1 + 2, D-dimer and C-reactive protein may function as markers of CSU severity. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Nonallergic drug hypersensitivities, also referred to as pseudoallergic or anaphylactoid reactions, have clinical manifestations that are often indistinguishable from allergic reactions. Methods: We performed a PubMed search using the terms 'drug allergy, drug hypersensitivity, pseudoallergies, anaphylaxis and nonallergic drug reactions' and reviewed 511 publications dated between 1970 and 2012. A total of 160 papers that were relevant to the most common nonallergic drug hypersensitivity reactions were selected for discussion. Results: Nonallergic drug hypersensitivities do not involve either IgE-mediated (type 1) or delayed (type 4) hypersensitivity. Nonallergic hypersensitivities are commonly referred to as pseudoallergic or idiosyncratic reactions. The common nonallergic drug hypersensitivities are secondary to chemotherapeutic drugs, radiocontrast agents, vancomycin, nonsteroidal anti-inflammatory agents, local anesthetic reactions and opiates. Protocols for skin testing of radiocontrast, nonsteroidal anti-inflammatory agents, local anesthetics and chemotherapeutic agents have been developed, though most have not been validated or standardized. Other diagnostic tests include in vitro-specific IgE tests, and the current 'gold' standard is usually an oral challenge or bronchoprovocation test. In the case of aspirin, even though it is not believed to be IgE-mediated, a 'desensitization' protocol has been developed and utilized successfully, although the mechanism of this desensitization is unclear. Conclusions: Diagnostic methods exist to distinguish allergic from nonallergic drug hypersensitivity reactions. The best option in nonallergic drug hypersensitivity is avoidance. If that is not possible, premedication protocols have been developed, although the success of premedication varies amongst drugs and patients. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Insect venoms contain an allergen hyaluronidase that catalyzes the hydrolysis of hyaluronan (HA), a polymer of disaccharide GlcUA-GlcNAc in skin. HAs depending on their size have variable function in inflammation and immunity. This paper reports on whether hyaluronidase, HA polymers and oligomers can promote antibody response in mice. Methods: HA oligomers (8- to 50-mer; 3-20 kDa) were obtained by bee venom hyaluronidase digestion of HA polymers (750- to 5,000-mer; 300-2,000 kDa). Antibody responses in mice were compared following 3 biweekly subcutaneous injection of ovalbumin (OVA) with or without test adjuvant. Results: OVA-specific IgG1 levels were approximately 2 times higher in BALB/c and C3H/HeJ mice receiving OVA and HA oligomer or polymer than those treated with OVA alone, and no increase in total IgE level was observed. In C57Bl/6 mice, observed increases in IgG1 and IgE were 3.5- and 1.7-fold, respectively, for the oligomer and 16- and 5-fold (p < 0.05), respectively, for the polymer. Conclusion: Hyaluronidase by its action on HA in skin can function indirectly as adjuvant to promote IgE and IgG1 response in mice. Insect venoms also have cytolytic peptides and phospholipases with inflammatory roles. These activities found in mice may contribute to venom allergenicity in susceptible people. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Over the last decade, a number of clinical practice guidelines that include guidance for the management of pediatric asthma have been introduced. The consistency across pediatric asthma guidelines is unknown and the emphasis on establishing asthma control may vary. The objective of this paper was to depict the evolution of guidelines for pediatric asthma and to compare current international guidelines in terms of their organization, presentation of evidence and consideration of children, with special emphasis on definitions of asthma control and severity. Methods: A systematic search to identify asthma guidelines was conducted, and guidelines were searched for pediatric terms. The approaches used by guidelines to define assessments of asthma severity and control were compared between the United States, the Global Initiative for Asthma, Canada, the United Kingdom and Australia. Results: Pediatric considerations in the management of asthma have been integrated into the various guidelines to different degrees and through varied strategies. There were differences in the conceptual and operational approach used to assess asthma which emphasized either asthma severity or control. Conclusions: It will be important for future guidelines to clearly define whether the primary assessment parameter is asthma severity or control. Delineating the guideline development process and supporting evidence may improve transparency, consistency and guideline adherence. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

For the diagnosis of allergy, cellular basophil activation tests (BAT), e.g. histamine or sulfidoleukotriene release tests, have long been introduced, but the expression of basophil activation markers such as CD63 and CD203c detected by flow cytometry has attracted more recent attention. A recent opinion paper in this Journal has stressed not only the potential but also the possible pitfalls of flow-cytometric BAT. We have applied clinical validation of various BAT in various ways for several years, and our experience shows that these new technologies have more potentials and perspectives than pitfalls. A comprehensive review of clinically validated studies on allergy to aeroallergens, insect venoms, latex, food allergens and drugs, e.g. myorelaxants, β-lactams, pyrazolones and non-steroidal anti-inflammatory drugs, as well as chronic urticaria shows clearly that even with different protocols, reproducible and meaningful results can be obtained. Although the available technologies may still be optimized and better standardized, there are no serious reasons to deprive allergic patients of clinically indicated BAT, which can be performed reliably by any laboratory with allergy and flow-cytometric capacity and expertise. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: The digestive system of Dermatophagoides farinae remains poorly documented. Methods: In this study, a three-dimensional (3-D) model of the alimentary canal of D. farinae was built for the first time based on hematoxylin-eosin staining, 76 cross-sections of the adult mite and 3-D reconstruction technology. Results: Spatially, the system included the prebuccal cavity, foregut, midgut, hindgut, anus and salivary gland. The prebuccal cavity was surrounded by gnathosoma; the foregut was composed of a muscular pharynx and an esophagus passing through the brain; the midgut was divided into an anterior midgut with a pair of ceca and a posterior midgut; the hindgut consisted of a relatively broad colon and a narrow rectum, and the salivary gland was irregular in shape and located in front of the brain. The 3-D images of the individual external surfaces of the reconstructed alimentary canal were displayed and the human-computer interaction was realized by performing arbitrary rotation and random sectioning. Conclusions: The 3-D model of the alimentary canal of D. farinae presented in this paper provides a stereoscopic view to study the adjacent relationship and arrangement of respective gut sections in the intact mite. This study has implicit impact on morphology studies, immunohistochemistry, as well as in situ PCR and localization of the allergen in dust mites. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Acquired angioedema (AAE) due to the functional deficiency of the C1 inhibitor (C1-INH) is a rare disease characterized by recurrent bouts of edema that involve subcutaneous tissues, the larynx or the gastrointestinal tract. In the present paper, we report the case of a male patient with symptoms of AAE and recurrent deep venous and arterial thrombosis. As a trigger of AAE in the present patient, we revealed primary antiphospholipid syndrome accompanied by antithrombin III deficiency, along with malignancy in the history, and angiotensin-converting enzyme inhibitor therapy. Although anti-C1-INH titers (type I AAE) were normal initially, we observed a sharp increase in anti-C1-INH titers (suggestive of type II AAE) during follow-up. It seems that thrombosis might worsen angioedematous attacks in functional C1-INH deficiency. Thrombophilia should be considered a provoking factor of AAE and should be carefully sought for in these patients, as the key to successful management of AAE is the effective treatment of the underlying disease. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Previous studies have shown a negative association between ACP1 *B/*C genotype and total IgE level. ACP1 (acid phospatase locus 1) is a polymorphic phosphotyrosine phosphatase that interacts with IL4-RA and is involved in T cell receptor signaling. Methods: In the present paper, we have studied the relationship between *B/*C genotype which shows high ACP1 activity and skin testing in 300 adult subjects referred for allergic manifestations. ACP1 genotypes were determined by DNA analysis. Results: There is a significant negative correlation between the intensity of skin test reaction and *B/*C genotype (p = 0.01). The proportion of *B/*C genotype is lower in allergic subjects with intense skin reaction than in allergic subjects with moderate skin reaction and in healthy controls. Conclusions: This new observation confirms by a different approach the relationship between ACP1 polymorphism and allergic manifestations, suggesting that high ACP1 activity protects against these manifestations. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: There has been an increasing prevalence of allergic diseases in the Western world over the last decades. The hygiene hypothesis has been proposed as a possible explanation for this epidemical trend in allergy. A key role in this theory is assigned to the reduced microbial stimulation of the Toll-like receptors (TLRs) in early life, which could lead to a weaker Th1 response and a stronger Th2 response to allergens. The individual immunological response is determined by the interplay between the dose and timing of exposure to endotoxins, other environmental factors and genetic predisposition. In the development and progression of allergic disorders, the innate immune system plays an important role. Objective: In this review, we discuss the paradoxical effects that may appear when the innate immune components are triggered. We review the influence of changes in the gene sequence and TLR expression in relation to the overall pattern of commensals and pathogens. We explored the possibility of alternative stimulations of the immune system by CpG oligodeoxynucleotides and probiotics as therapeutic devices against this endemic disease in Western society. Methods: Selection of papers was based on the importance of their contribution to the understanding of innate immunity and its implications. Results and Conclusion: The innate immune system plays an important role in both the protection against and the enhancement of allergic disorders, but the mechanisms are still unclear. Nevertheless, gene polymorphisms and triggers of the innate immune system provide therapeutic targets for protection against and treatment of allergic disorders. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Over the last decade several papers have dealt with the possible interference of allergies in both the infectious disease incidence and tumour development. In the light of all these observations we analysed several tumour patients for a possible interaction between a state of allergy and tumour development and progression after primary cancer therapy. Methods: This study included 1,055 patients with different types of solid tumours admitted consecutively between 1994 and 2002 to the Cagliari University Polyclinic. After primary surgery or medical therapy (or both), 92 allergic subjects and 182 non-allergic patients were studied over a follow-up period of 6–96 months (median 23). Results: Among 1,055 tumour-bearing patients, the prevalence of allergy was found to be about 8% versus 16–37% in a population of non-tumour-bearing subjects. After primary cancer therapy, allergic patients turned out to have a 20% higher probability of being cured and about a 50% lower risk of tumour progression as compared to non-allergic ones. The observed differences were statistically significant (p = 0.013). Conclusions: On the basis of our findings, we suggest that allergic subjects seem to have a better prognosis than non-allergic ones for disease outcome after cancer therapy. Copyright © 2004 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

In recent years, there has been growing interest in the application of immunotherapy as an alternative to chemotherapy and radiotherapy for the treatment of malignant diseases. This interest is due to a variety of factors, including revival of the immunosurveillance theory, availability of well-defined and structurally characterized human tumor-associated antigens (TAAs), progress in our understanding of the molecular pathways required for induction and maintenance of an immune response, and advances in methodologies to generate TAA-specific cytotoxic T lymphocytes (CTLs) and monoclonal antibodies (mAbs) as immunological probes. However, contrary to the positive results obtained with TAA-specific immunotherapy in animal model systems, the clinical response in patients has been disappointing. Frequently, the immune responses do not correlate with the clinical responses. Analysis of the underlying mechanisms of this dichotomy have identified the low immunogenicity of TAAs, the lack of immunological markers to predict clinical outcomes, and the ability of tumors to escape immune recognition and destruction as challenges to the development and application of immunotherapy. In this paper, we have reviewed the mechanisms underlying immune unresponsiveness to TAAs and strategies to overcome this unresponsiveness in the humoral and cellular immune responses, highlighting findings from different antigenic systems to prove the validity of these strategies. Additionally, we have addressed limitations to TAA-targeting immunotherapy as a result of the genetic instability of tumor cells, and have discussed strategies to overcome this limitation by targeting immunotherapy to molecules implicated in tumor-associated angiogenesis. Lastly, we have concluded by indicating the need to refine the implementation of clinical trials of immunotherapy, and to emphasize combination therapies to counteract the multiple tumor escape mechanisms. Copyright © 2003 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]