Specific IgE Responses Research Articles

Depletion of CD4+CD25+ T cells switches the whey‐allergic response from immunoglobulin E‐ to immunoglobulin free light chain‐dependent

Symptoms of allergy are largely attributed to an IgE-mediated hypersensitivity response. However, a considerable number of patients also exhibit clinical features of allergy without detectable systemic IgE. Previous work showed that Ig-free light chains (IgLC) may act as an alternate mechanism to induce allergic responses. CD4+CD25+ T cells are crucial in the initiation and regulation of allergic responses and compromised function might affect the response to allergens. To examine the contribution of CD4+CD25+ T cells and IgLC towards the whey-allergic response. Mice were sensitized orally with whey using cholera toxin as an adjuvant. CD25+ T cells were depleted in vivo using a CD25 mAb. The acute allergic skin response to whey and ex vivo colon reactivity was measured in the presence or absence of F991, a specific inhibitor of IgLC. Serum whey-specific antibodies and IgLC in serum and mesenteric lymph node (MLN) supernatants were measured. Depletion of CD4+CD25+ T cells was confirmed in the spleen. Anti-CD25 treatment strongly reduced whey-specific antibody levels and resulted in a partial depletion of effector T cells and a major depletion of Foxp3(+) regulatory T cells. Surprisingly, despite the abolished specific IgE response, the acute allergic skin response to whey was not affected. IgLC levels were enhanced in the serum and MLN supernatants of CD25-depleted sensitized mice. F991 inhibited the acute skin response and colon hyperreactivity in anti-CD25-treated mice, indicating that these responses were mainly IgLC dependent. Depletion of CD4+CD25+ T cells resulted in a switch from an IgE- to an IgLC-dependent acute skin response and functional hyperresponsiveness of the colon. Our data suggest that CD25+ T cells play a crucial role in balancing cow's milk allergy between IgE and IgE-independent responses and both mechanisms might play a role in allergic responses to the same allergen.

Recombinant Allergens Combined with Biological Markers in the Diagnosis of Allergic Bronchopulmonary Aspergillosis in Cystic Fibrosis Patients

Allergic bronchopulmonary aspergillosis (ABPA) is a frequent complication in cystic fibrosis patients. The diagnosis remains difficult and requires a combination of clinical, radiological, biological, and mycological criteria. The aim of this study was to analyze the added value of two recombinant antigens, rAspf4 and rAspf6, associated with the detection of specific IgG; precipitins; total IgE; and Aspergillus fumigatus in sputum for the diagnosis of ABPA. In a retrospective study, we determined the specific IgE responses to these recombinants in 133 sera of 65 cystic fibrosis patients. We selected an average of five serum samples from each of the 17 patients with ABPA (13 proven and 4 probable ABPA) and from 3 patients with Aspergillus bronchitis and rhinosinusitis. One serum sample for the 45 patients without ABPA was tested. The sensitivity of specific IgE detection against rAspf4 calculated per patient (92.3%) was significantly higher (P < 0.05) than that of rAspf6 (53.8%). When rAspf4 IgE detection was associated with anti-Aspergillus IgG enzyme-linked immunosorbent assay (ELISA) and precipitin detection, the sensitivity rose to 100%. The specificities of rAspf4 and rAspf6 IgE detection were 93.7% and 91.6%, respectively. Other diagnostic criteria had slightly lower specificities (87.5% for anti-Aspergillus IgG ELISA, 89.6% for precipitins, 84.4% for total IgE, and 85.0% for positive A. fumigatus culture in sputum). In conclusion, this retrospective study showed the relevance of rAspf4 IgE detection, in combination with other biological markers (Aspergillus IgG ELISA, precipitins, and total IgE), for improving the biological diagnosis of ABPA.

Association of allergic sensitization with infectious diseases burden in Roma and non-Roma children

The hypothesis whether exposure to certain infections protects from atopy remains equivocal. To further investigate this, we compared serologic markers of infection and allergic sensitization prevalence in Roma children, who live under unfavorable hygienic conditions that facilitate the spread of infections, and non-Roma children who live in the same area. Analyses included 98 Roma and 118 non-Roma children. Serum IgG antibodies for 13 foodborne- airborne- and bloodborne infectious agents were determined, and a cumulative index of exposure was calculated by adding one point for each positive infection. Specific serum IgE to certain common food- and aero-allergens was also tested. and positivity to any of them was defined as indication of atopy. Roma children were found significantly more seropositive for T. gondii, Hepatitis A, H. pylori, HSV-1, CMV, and Hepatitis B (p < 0.0001). Non-Roma children were found more seropositive for RSV and M. pneumonia (p < 0.0001). Regarding the overall prevalence of atopy or the specific IgE responses to the allergens tested, no statistically significant differences were found between Roma and non-Roma children. A positive association of the cumulative index of exposure to infections with atopy was found in the non-Roma children (OR: 1.38, 95% CI: 1.08-1.75, p = 0.01) and in the total population (OR: 1.42, 95% CI: 1.11-1.83, p = 0.01). Regarding the specific infectious agents tested, a statistically significant positive association of atopy with seropositivity was found for M. pneumoniae in the non-Roma children (OR: 3.93, 95% CI: 1.39) as well as in the total population studied (OR: 2.83, 95% CI: 1.32-6.07, p = 0.01). Despite the higher burden of exposure to the battery of the infectious agents tested among Roma children, no protective effect for allergic disease development was evident. On the contrary, a positive association of exposure to infections with evidence of atopy was found, especially evident in the non-Roma children.

Obesity, insulin resistance and the prevalence of atopy and asthma in US adults

The roles of obesity and insulin resistance in asthma and atopy are not well understood. We investigated whether there is an association of obesity and insulin resistance with asthma and atopy prevalence in US adults. Data from the 2005-2006 National Health and Nutrition Examination Survey were analyzed by multivariate logistic regression, controlling for sex, age, ethnicity, income, and smoking status. Obesity was measured by body mass index (BMI) and waist circumference, and insulin resistance by the homeostasis model assessment. Asthma was defined by self-report of ever receiving a diagnosis and still having asthma currently, and atopy by any positive specific serum IgE responses to a panel of aeroallergens. Neither obesity measure nor insulin resistance was associated with atopy. Obesity was positively associated with asthma overall (odds ratio [OR] for obese vs normal BMI = 2.28, 95% CI: 1.76, 2.96; OR for obese vs normal waist circumference = 1.75; 95% CI: 1.22, 2.51) but insulin resistance was not (OR = 1.26; 95% CI: 0.80, 1.98). Obesity was also associated with nonatopic asthma (OR for obese vs normal BMI = 2.5; 95% CI: 1.2, 5.2; OR for obese vs normal waist circumference = 2.07, 95% CI: 1.21, 3.54), while obese BMI was also associated with atopic asthma (OR = 2.04, 95% CI: 1.37, 3.03). Obesity remained independently associated with all asthma outcomes after controlling for insulin resistance. Obesity was independently associated with asthma, and atopic and nonatopic asthma, after controlling for insulin resistance and socio-demographic factors. There was no evidence that insulin resistance was associated with atopy or asthma.

Enteric reovirus infection stimulates peanut-specific IgG2a responses in a mouse food allergy model

IgE-mediated food allergies are an important cause of life-threatening hypersensitivity reactions. Orally administered peanut antigens mixed with the mucosal adjuvant cholera toxin (CT) induce a strong peanut extract (PE)-specific serum IgE response that is correlated with T-helper type 1 (Th1) and type 2 (Th2)-like T-cell responses. This study was conducted to determine if respiratory enteric orphan virus (reovirus), a non-pathogenic virus that induces robust Th1-mediated mucosal and systemic responses could modulate induction of PE-specific allergic responses when co-administered with PE. Young mice were orally exposed to PE mixed with CT, reovirus, or both CT and reovirus. As expected, CT promoted PE-specific serum IgE, IgG1, and IgG2a and intestinal IgA production as well as splenic Th1- and Th2-associated cytokine recall responses. Reovirus did not alter PE-specific serum IgE and IgG1 levels, but substantially increased the PE-specific IgG2a response when co-administered with PE with or without CT. Additionally, reovirus significantly decreased the percentage of the Peyer’s patch CD8 + T-cells and Foxp3 +CD4 + T-regulatory cells when co-administered with PE. These results demonstrate that an acute mucosal reovirus infection and subsequent Th1 immune response is capable of modulating the Th1/Th2 controlled humoral response to PE. The reovirus-mediated increase in the PE-specific IgG2a antibody response may have therapeutic implications as increased levels of non-allergenic PE-specific IgG2a could block PE antigens from binding to IgE-sensitized mast cells.

FcγRIIb Inhibits Allergic Lung Inflammation in a Murine Model of Allergic Asthma

Allergic asthma is characterized by airway eosinophilia, increased mucin production and allergen-specific IgE. Fc gamma receptor IIb (FcγRIIb), an inhibitory IgG receptor, has recently emerged as a negative regulator of allergic diseases like anaphylaxis and allergic rhinitis. However, no studies to date have evaluated its role in allergic asthma. Our main objective was to study the role of FcγRIIb in allergic lung inflammation. We used a murine model of allergic airway inflammation. Inflammation was quantified by BAL inflammatory cells and airway mucin production. FcγRIIb expression was measured by qPCR and flow cytometry and the cytokines were quantified by ELISA. Compared to wild type animals, FcγRIIb deficient mice mount a vigorous allergic lung inflammation characterized by increased bronchoalveolar lavage fluid cellularity, eosinophilia and mucin content upon ragweed extract (RWE) challenge. RWE challenge in sensitized mice upregulated FcγRIIb in the lungs. Disruption of IFN-γ gene abrogated this upregulation. Treatment of naïve mice with the Th1-inducing agent CpG DNA increased FcγRIIb expression in the lungs. Furthermore, treatment of sensitized mice with CpG DNA prior to RWE challenge induced greater upregulation of FcγRIIb than RWE challenge alone. These observations indicated that RWE challenge upregulated FcγRIIb in the lungs by IFN-γ- and Th1-dependent mechanisms. RWE challenge upregulated FcγRIIb on pulmonary CD14+/MHC II+ mononuclear cells and CD11c+ cells. FcγRIIb deficient mice also exhibited an exaggerated RWE-specific IgE response upon sensitization when compared to wild type mice. We propose that FcγRIIb physiologically regulates allergic airway inflammation by two mechanisms: 1) allergen challenge mediates upregulation of FcγRIIb on pulmonary CD14+/MHC II+ mononuclear cells and CD11c+ cells by an IFN-γ dependent mechanism; and 2) by attenuating the allergen specific IgE response during sensitization. Thus, stimulating FcγRIIb may be a therapeutic strategy in allergic airway disorders.

Changes in asthma‐like responses after extended removal from exposure to trimellitic anhydride in the Brown Norway rat model

Organic acid anhydride-induced occupational asthma is considered to be IgE-mediated. Airway and skin exposure are the two main routes of sensitization in the work place. Recently we developed an allergic asthmatic Brown Norway rat model sensitized by dermal exposure to trimellitic anhydride (TMA) using an occlusion patch application. The objectives of this study were (1) to develop a model of non-occluded dermal exposure leading to allergic sensitization and (2) to examine the effect of extended removal from exposure on persistence of both specific IgE and TMA aerosol-induced airway responses in this model. TMA powder (4 or 40 mg) was applied, unoccluded, to the skin of rats for 4 h, once/week for 4 weeks. Rats were given a 10-min aerosol challenge to 40 mg/m(3) TMA 2 weeks after the last dermal exposure (day 35). Another group was challenged on day 35 and again 18-24 months later. Respiratory enhanced pause (Penh), pulmonary histopathology and inflammation and specific IgE titres were measured. Rats produced dose-dependent specific IgE titres after exposure and developed early-phase (EAR) and late-phase airway responses (LAR) after airway challenge to TMA aerosol as well as airway eosinophilic inflammation. Specific airway responses were still manifested after a second TMA airway challenge given 18-24 months following the initial airway challenge. While persistent, airway inflammation, specific IgE and EAR were significantly attenuated following the second TMA challenge. LAR remained robust at 18-24 months and was not significantly different from the response on day 35. These results demonstrate the persistence of chemical sensitization and further suggest that IgE is not essential for LAR.

Associations between decay‐accelerating factor polymorphisms and allergic respiratory diseases

Allergic diseases such as asthma and allergic rhinitis are major causes of morbidity in developed countries. The pathology underlying allergic respiratory diseases is considered to be IgE-mediated type I allergy characterized by mucosal inflammation that occurs in response to allergen exposure. They are common diseases involving a complex inheritance. Complement systems are known to play an important role in allergic diseases. Decay-accelerating factor (DAF) is important for the regulation of the complement system and is a good candidate for determining the susceptibility to allergic diseases. The present study aimed to investigate whether polymorphisms in the DAF gene are associated with allergic respiratory diseases in the Japanese population. We performed mutation screenings of DAF and conducted a tag single-nucleotide polymorphisms (SNP) association analysis for 684 unrelated adult individuals with seasonal allergic rhinitis (SAR) with Japanese ceder pollen, 188 mite-sensitive adults with asthma, and 346 unrelated non-allergic healthy controls. DAF is located in the tight linkage disequilibrium (LD) block spanning 62 kb. The tag SNP analysis revealed that rs10746463 was significantly associated with SAR (P=0.00033) and mite-sensitive adult asthma (P=0.044). The rs2564978 and rs3841376 haplotypes, which are located in the promoter region of DAF, were in complete LD with rs10746463 (r2=1). Luciferase reporter assays with constructs containing the 5' flanking regions of DAF showed that the plasmid with rs2564978 C/rs3841376 deletion (the risk haplotype) had a statistically significantly lower transcriptional activity than that containing the rs2564978 T/rs3841376 insertion. Our results suggest that DAF is one of the genes involved in conferring susceptibility to allergic respiratory diseases and show that decreased levels of DAF may be associated with the enhanced specific IgE responses occurring in allergic diseases in the Japanese population.

The HLA DRB1*1501-DQB1*0602-DPB1*0501 Haplotype Is a Risk Factor for Toluene Diisocyanate-Induced Occupational Asthma

Background: Although the pathogenesis of toluene diisocyanate (TDI)-induced occupational asthma (TDI-OA) is incompletely understood, several studies have suggested immunologic mechanisms, including specific IgE responses. A few studies have suggested human leukocyte antigen (HLA) associations with TDI-induced asthma in Western countries, but this is the first investigation of associations between HLA class I and II alleles and TDI-induced asthma patients in Asia, using high-resolution analysis. Methods: Patients with TDI-OA (n = 84), asymptomatic exposed controls (AECs, n = 47) and unexposed normal controls (NCs, n = 127) were enrolled. HLA class I and II genotyping was performed by the direct DNA sequencing analysis. Specific serum IgE antibodies to the vapor type TDI-albumin conjugate were measured by ELISA. Results: There was no significant association between the allele frequencies and the phenotype of TDI-OA. However, the frequency of the HLA DRB1*1501-DQB1*0602-DPB1*0501 haplotype was significantly higher in TDI-OA patients (19%) than in AEC (2.1%, p = 0.007, OR 4.429, CI 1.497–13.103) or NC (3.1%, p < 0.001, OR 7.235, CI 2.236–22.510) subjects, with statistical significance persisting after correction for multiple comparisons. DQB1*0402 was significantly associated with the presence of specific IgE to TDI-albumin conjugates in serum (p = 0.006, OR 4.552, CI 1.540–13.449). This p value remained significant after correction for multiple comparison. Conclusion: The HLA DRB1*1501-DQB1*0602-DPB1*0501 haplotype may be a genetic marker for the development of TDI-induced asthma in Koreans. Several HLA alleles that enhance specific IgE sensitization in exposed subjects are indicated.

Specific IgE and IgG Responses and Cytokine Profile in Subjects with Allergic Reactions to Biting Midge Forcipomyia taiwana

Background:Forcipomyia taiwana is a tiny blood-sucking midge whose habitat covers large parts of Taiwan and southern China. Female midges bite during the day, causing intense pruritis and swelling in allergic individuals. In this study, we investigated the immune responses of different allergic reactions to midge bites. Methods:F. taiwana (midge)-specific IgE, -IgG and -IgG subclasses were examined by ELISA in 62 human subjects. Peripheral blood mononuclear cells (PBMC) from 6 subjects with solely delayed reactions (SDR) to midge bites and 6 nonallergic controls (NAC) were cultured with midge extract at various time points and assayed. Proliferation of PBMC was measured by MTT assay. Expression of cytokine mRNA was measured by real-time PCR and protein levels by cytometric bead immunoassay or ELISA. Protease activity in midge extract was determined by the Azocoll method. Results: Midge-specific IgE among subjects with an immediate reaction were significantly elevated compared to SDR and NAC subjects. There were no differences in the level of midge-specific-IgG, -IgG₁, -IgG₂, -IgG₃ and -IgG₄ among subjects with different biting reactions. Midge extract elicited significantly more PBMC proliferation, higher expression of IFN-γ, IL-10, IL-6 and TNF-α in SDR subjects than in NAC. Protease activity was detected in midge extract. Protease inhibitors E64 and pepstatin suppressed midge-extract-induced IL-8 production. Conclusions: Our results suggest that an immediate reaction to midge bites is IgE-mediated. IFN-γ, IL-6 and TNF-α are involved in delayed reactions to midge bites. A protease-activated pathway may also be involved in the intense, itchy reactions to midge bites.

Bronchiolitis

: Diagnostic criteria for bronchiolitis are variable. : To study how the risk factors for recurrent wheezing and asthma vary by different definitions of bronchiolitis. : Viral etiology and atopic characteristics were studied in 259 hospitalized wheezing children (median age, 14 months; range, 0-36 months). The data were analyzed according to age (<6, <12, <24 and <36 months) and whether they had a history or no history of a previous wheezing episode. Sixteen viruses were detected by conventional and molecular methods. Atopic characteristics included the presence of eczema, specific and total IgE responses, blood eosinophil count, and modified asthma predictive index. : Evidence of respiratory virus infection was found in 93% of the cases and allergic sensitization in 26% of the cases. Rhinovirus infections and atopic characteristics (sensitization, blood eosinophil count, and modified asthma predictive index) increased by age and were significantly more common in children with recurrent wheezing episodes than in first-time wheezers in age categories of <24 and <36 months (P < 0.05 for all). : In children with bronchiolitis, 2 clinical factors, age and number of previous wheezing episodes, are linked to inflammatory (atopy-related factors) and virologic risk factors of asthma (rhinovirus-associated disease). According to current US and UK guidelines, bronchiolitis includes wheezing children <24 months of age. Our observations suggest that the clinical definition should include only children with their first episode of wheezing.

Specific IgE Response to Trichophyton and Asthma Severity

Sensitization to Trichophyton, a major dermatophyte, has been associated with asthma. Whether such sensitization is generally associated with the severity of asthma, like other molds such as Alternaria, is unknown. We compared 258 patients with asthma, which was classified by severity as mild (n = 123), moderate (101), or severe (34), and 114 healthy control subjects, with regard to specific IgE titers against Trichophyton rubrum and other common allergens such as mixed molds, house-dust mite, cat dander, dog dander, Japanese cedar pollen, mixed Graminea pollens and mixed weed pollens. Positive rate of Trichophyton-specific IgE was higher in the patients with moderate asthma (15.8%) than in the control subjects (7.0%, p = 0.04) and patients with mild asthma (4.9%, p < 0.006), and it was also higher in the patients with severe asthma (32.4%) than in control subjects (p = 0.0001), and patients with mild asthma (p < 0.0001) and moderate asthma (p = 0.04), but it did not differ between the control subjects and patients with mild asthma. The positive rates of mixed molds, cat dander, and dog dander were almost invariably higher in patients in all asthma subgroups than in the control subjects but did not differ among patients in the three asthma subgroups. The positive rates of other allergens were not different in all groups. Reanalysis of positive rate of Trichophyton-specific IgE after excluding 52 subjects with positive results for mixed molds showed a similar statistical trend to that of the original cohort. This may negate the potential effect of cross-reactivity to these molds. Multivariate analysis of asthma subgroups identified positive IgE results for Trichophyton as an independent determinant of asthma severity. Specific IgE response to Trichophyton may be associated with more severe asthma.

Induction of Th1-Type Immune Response by Chitosan Nanoparticles Containing Plasmid DNA Encoding House Dust Mite Allergen Der p 2 for Oral Vaccination in Mice

This study was to prepare the chitosan-pDer p 2 nanoparticles and to investigate the effect of chitosan-DNA nanoparticles on immune response in mice by oral delivery of chitosan-DNA nanoparticles. The nanoparticles were synthesized by complexing chitosan with plasmid DNA. The DNA was fully complexed into chitosan-DNA nanoparticles, suggesting a 100% encapsulation efficiency. Chitosan-DNA complex renders a significant protection of the plasmid. No effect on cell viability was observed in both cell types and average cell viability over 100% was obtained. Oral gene delivery with chitosan-DNA nanoparticles can generate a higher level expression of gene in vivo. Oral chitosan-pDer p 2 nanoparticles in BALB/c mice can induce IFN-gamma in serum and prevent subsequent sensitization of Th2 cell-regulated specific IgE responses. The data indicate that the oral administration of chitosan-pDer p 2 nanoparticles results in the expression of Der p 2 in the epithelial cells of both stomach and small intestine and the induction of Th1-type immune response.

Modulation of Antigen-Induced Anaphylaxis in Mice by a Traditional Chinese Medicine Formula, Guo Min Kang

A traditional Chinese Medicine (TCM) formula, Guo Min Kang (GMK), has been used in clinics in China for allergic diseases, including type I immediate hypersensitivity, a potentially fatal disease, but its modulatory mechanism remains elusive. The aim of this study was to investigate the modulatory mechanisms of GMK in a mouse model of Ag-induced anaphylaxis. Ag (conalbumin) sensitized mice were treated with either PBS (sham) or GMK before (schedule A) or during (schedule B) sensitization, and various anaphylactic parameters were measured following Ag challenge, including symptom score, cutaneous hypersensitivity response, mast cell degranulation, plasma histamine levels and the levels of specific IgE and T-cell responses. Systemic anaphylaxis was investigated in mice immediately following Ag challenge, and the results showed that GMK-treated mice from both treatment schedules A and B showed significantly reduced symptom scores when compared with the sham-treated group. The reduction in symptom score was associated with a significant reduction in the level of Ag-induced cutaneous immediate hypersensitivity. Also, GMK was able to suppress Ag-induced IgE production and T-cell responses, while it spares mitogen (Con A)-induced T-cell response. Further, treatment of mice with GMK abrogated the levels of Ag-induced histamine release and significantly reduced the number of degranulated mast cells. No effect of GMK was observed on the levels of total IgE and plasma histamine in naive mice. These results provide a basis for the modulation effect of GMK and suggest a potential utility of GMK as a prophylactic and therapeutic agent.

Characteristics of Nonallergic Vasomotor Rhinitis

Nonallergic rhinitis (NAR) conditions are currently considered diagnoses by exclusion. A diagnosis of NAR requires negative specific IgE responses by skin or serologic testing and more recently testing to exclude localized production of specific IgE in the nose. Symptoms are classically aggravated by irritant triggers such as tobacco smoke, perfumes/fragrances, and temperature or barometric pressure changes. A previously developed questionnaire survey designed to help physicians recognize differences between allergic rhinitis and nonallergic rhinitis subtypes found that patients with symptom onset later in life (> 35 years), no family history of allergies, no seasonality or cat-induced symptoms, and symptoms induced by perfumes and fragrances had > 95% likelihood of having a physician diagnosis of NAR. Of note, clinical symptoms were not generally useful for differentiating chronic rhinitis subtypes which has also been confirmed in a more recent study investigating the relationship between headaches and chronic rhinitis subtypes (Table 1). In subsequent studies it was found that a significant percentage of NAR patients did not experience irritant-induced symptoms, suggesting that these triggers are not a clinical characteristic that can be uniformly used for all NAR patients. However, a newly developed Irritant Index Scale can be used to reliably differentiate pure allergic rhinitis from nonallergic rhinitis with trigger phenotypes. The use of standardized and validated questionnaires allows objective characterization of chronic rhinitis subtypes that appears to improve the accuracy of clinically diagnosing these patients.

Genetic Impact of a Butyrophilin-like 2 (BTNL2) Gene Variation on Specific IgE Responsiveness to Dermatophagoides farinae (Der f) in Japanese

Dermatophagoides farinae (Der f) is one of the most frequently implicated allergens in several allergic diseases. Several genome-wide screens have identified a linkage between chromosome 6p21 and mite-specific IgE responsiveness. Butyrophilin-like 2 (BTNL2) is a member of the immunoglobulin superfamily and, on the basis of its homology to B7-1, has been implicated as a costimulatory molecule involved in T-cell activation. BTNL2 resides in the HLA region on chromosome 6p21, and significant associations between BTNL2 gene polymorphisms and several inflammatory diseases have been reported. The aim of this study was to examine whether BTNL2 gene polymorphisms are associated with specific IgE responses to Der f. Three single nucleotide polymorphisms (SNPs), including 2 coding SNPs and 1 intron SNP, were studied. One of the coding SNPs was the rs2076530 A > G, which has a functional consequence. A total of 863 unrelated Japanese subjects (447 positive and 416 negative for IgE to Der f) were recruited for a case-control study. Controlling for gender, age, smoking, and the presence of asthma, multiple logistic regression analyses showed that homozygosity of the rs2076530 A allele, which has been reported to be a risk allele for sarcoidosis, was associated with a risk of sensitization towards Der f (Odds ratio; 1.55, p = 0.0060). Although an association which may be due to the linkage disequilibrium with other genes in 6p21 needs to be ruled out, the present findings suggest that the BTNL2 gene might be one of the candidate genes that is responsible for the pathogenesis of Der f-specific IgE responsiveness.

IgE response to staphylococcal enterotoxins in adenoid tissues from atopic children

To evaluate local production of staphylococcal superantigen (SAg)-specific IgE in adenoid tissue and to compare its prevalence with that in the tonsil and serum, as well as its relationship with markers of allergic inflammation within adenoid tissue. Prospective randomized study. We recruited 18 atopic children who had rhinitis symptoms and were sensitized to more than one common aeroallergen, and 22 nonatopic children undergoing adenotonsillectomy. Immunoassays were performed using adenoid tissue homogenate to quantify the levels of three staphylococcal SAg-specific IgE (SEA, SEB, and TSST-1), total IgE, eosinophil cationic protein (ECP), mast cell tryptase, and soluble CD23. Three kinds of SAg-specific IgE were detected in the adenoid and tonsil tissues of atopic patients, but not in those of nonatopic patients. In atopic children, the prevalence of SEA-, SEB-, and TSST-1-specific IgE in adenoid tissues (61.1%, 27.8%, 33.3%, respectively) were higher than those in tonsil tissues (38.9%, 5.6%, 11.1%, respectively) and in sera (11.1%, 27.8%, 16.7%, respectively). Subjects with high SEA levels showed significantly higher serum and adenoid total IgE, with higher eosinophilia. Significant correlations were noted between SAg-specific IgE levels and tryptase levels in adenoid tissue. Local specific IgE response to staphylococcal SAgs, especially SEA may contribute to ongoing allergic inflammation in adenoid tissue from atopic children.

Food Allergy: From the of Loss of Tolerance Induced by Exclusion Diets to Specific Oral Tolerance Induction

The prevalence of food allergy and anaphylaxis in children is reported to be increasing in recent years. Evidence suggests that exposure to large doses of antigen might produce a suppression of the specific IgE response, so that the continuous contact with high doses of antigens favours the maintenance of tolerance In the same way loss of contact with allergen in children with specific IgE reactivity may favour a loss of tolerance with development of systemic reactions, while a progressive new contact with allergen may favour a specific tolerance induction. We hypothesize that widespread and uncontrolled use of elimination diets for atopic dermatitis may have played a role in the increase of allergy and anaphylaxis. Specific oral tolerance induction may be a possible therapeutic strategy. The article review food allergies caused by exclusion diet and also discuss recent patents related to the field.

Galectin and aldolase‐like molecules are responsible for the specific IgE response in humans exposed to Dirofilaria immitis

Dirofilaria immitis is the agent of the heartworm disease in canids and felids, and of pulmonary dirofilariosis in man. Like other filariae, D. immitis harbours endosymbion Wolbachia bacteriae. In this work we analyse the response of specific IgE antibodies against both D. immitis antigens and the Wolbachia surface protein (WSP) in two groups of persons living in an area of canine endemia, one presenting high levels of total IgE (group 1) and other with normal levels (group 2). Infections with D. immitis were demonstrated by the presence of specific IgG in 228 individuals(48.8%) of the group 1 and only in one of the group 2. Specific IgE antibody response against D. immitis antigens was detected only in individuals of the group 1. IgE response against WSP was not detected in any group. The IgE response was directed mainly against two molecules of 33 and 42 kDa of the antigenic extract of D. immitis. These molecules were identified by mass spectrometry as a galectin and an aldolase, respectively. Their possible role in the survival mechanisms of the parasite and their contribution to development of allergic reactions in individuals resident in areas with heartworm disease are discussed.

Ascaris lumbricoides-induced suppression of total and specific IgE responses in atopic subjects is interleukin 10-independent and associated with an increase of CD25 + cells

Ascaris presence in humans has been associated with high levels of blood eosinophils and serum IgE. This study was designed to address the influence of Ascaris infection on allergic and inflammatory parameters of atopic subjects. A cross-sectional design was used, and atopic individuals to be assessed were divided into 3 groups including Ascaris-infected, anti- Ascaris IgG-positive (seropositive), and control subjects. All subjects enrolled had positive skin test reactivity to at least 1 perennial or seasonal allergen; however, levels of C-reactive protein, C 3, and C 4 were within normal range values. Eosinophil percentage was not significantly different among the groups studied. Total IgE and specific anti- Ascaris IgE levels in the seropositive group were significantly higher than concentrations found in both control and infected groups. Interleukin (IL)-4 release in Ascaris-infected patients was significantly increased versus seropositives, who were able to produce more IL-4 than controls. The levels of IL-10 were lower in the seropositives as well as infected subjects in comparison with controls. CD25 + lymphocyte populations were significantly increased in the infected group versus the seropositives as well as the controls. Lung function tests of some selected seropositive subjects were significantly impaired. The same parameters of a representative infected patient were not different from controls. Our data on T helper type 2 cells (Th2) and regulatory T cells (Treg) features, as well as CD25 + lymphocyte increase, suggest an Ascaris-induced mechanism leading to parasite survival. Moreover, the stable control of both T helper type 1 cells (Th1) and Th2 immunity cascades, paralleled by the absence of overwhelming inflammatory systemic reactions and lack of allergic syndromes, may result in a favorable host condition.