Specific IgE Responses Research Articles

Suppression of dust mite allergy by mucosal delivery of a hypoallergenic derivative in a mouse model.

Allergic asthma caused by house dust mite (HDM) is becoming a public health problem. Specific immunotherapy is considered to be the only curative treatment, but it is always associated with IgE-mediated side effects in the therapy process. A few studies showed that the disruption of allergen IgE epitopes could reduce IgE reactivity and thus reduce allergenic activity. In this study, a hypoallergenic derivative of the major HDM allergen Der p2 was constructed by genetic engineering. This derivative was confirmed to have a considerably reduced IgE reactivity compared with Der p2. For its application in vivo, recombinant Lactococcus lactis (LL-DM) was engineered to deliver the Der p2 derivative to the intestinal mucosal surface. Oral administration of LL-DM significantly alleviated Der p2-induced airway inflammation, as shown by reduced inflammatory infiltration and a reduction in Th2 cytokines in bronchoalveolar lavage. This protective effect was associated with an up-regulation of specific IgG2a and a decrease in IL-4 level in the spleen which may affect specific IgE response. Moreover, the levels of regulatory T cells in the mesenteric lymph nodes and spleen were markedly increased in mice fed with LL-DM, suggesting that LL-DM can inhibit allergic responses via the induction of regulatory T cell. Our results indicate that the Der p2 derivative is a promising therapeutic molecule for specific immunotherapy and recombinant lactic acid bacteria could be developed as a promising treatment or prevention strategy for allergic diseases.

Substance P (subP) and Minocycline Suppress Induction of Human Ragweed Specific Memory IgE Responses By Different Mechanisms

RationaleWe reported that CD4+ and CD8+CD60+ T cells and 6 cytokines, including IL-4, were required for ragweed specific (RS) memory IgE responses by PBMC of ragweed sensitized humans, and that minocycline strongly suppressed T cell expression of phosphorylated p38 MAP kinase (p38MAPK) and IL-4, while preventing induction of RS memory IgE responses. Others previously reported that CD4+ T cells and IL-4 were required for human IgE responses and that p38MAPK is associated with IL-4. We hypothesize that subP, previously shown to suppress murine memory IgE responses, will prevent induction of human RS memory IgE responses.MethodsPBMC were obtained from ragweed sensitized humans (n=4-6) and CD4+IL-4+ and CD8+CD60+IL-4+ T cell numbers determined ± incubation with PMA/ionophore. The effect of subP ± PMA/ionophore on these cells, on CD4+p38MAPK+ T cells, and on RS memory IgE responses were determined (flow cytometry, ELISA).ResultsCD4+IL-4+ T cells were 5% of CD4+ T cells; CD8+CD60+IL4+ T cells were >99% of CD8+CD60+ T cells. SubP did not suppress CD4+IL-4+ or CD8+CD60+IL-4+ T cells. Nevertheless, subP suppressed T cell p38MAPK (30-70%) and induction of RS memory IgE responses. As reported, minocycline strongly suppressed IL-4, T cell p38MAPK and RS memory IgE responses.ConclusionsSubP and minocycline appear to suppress RS memory IgE responses by different mechanisms. SubP did not suppress IL-4 but minocycline did. Both suppressed IgE responses. It is possible that subP suppresses events occurring downstream of IL-4. Further, it is possible that subP suppresses other cytokines required for memory IgE responses. RationaleWe reported that CD4+ and CD8+CD60+ T cells and 6 cytokines, including IL-4, were required for ragweed specific (RS) memory IgE responses by PBMC of ragweed sensitized humans, and that minocycline strongly suppressed T cell expression of phosphorylated p38 MAP kinase (p38MAPK) and IL-4, while preventing induction of RS memory IgE responses. Others previously reported that CD4+ T cells and IL-4 were required for human IgE responses and that p38MAPK is associated with IL-4. We hypothesize that subP, previously shown to suppress murine memory IgE responses, will prevent induction of human RS memory IgE responses. We reported that CD4+ and CD8+CD60+ T cells and 6 cytokines, including IL-4, were required for ragweed specific (RS) memory IgE responses by PBMC of ragweed sensitized humans, and that minocycline strongly suppressed T cell expression of phosphorylated p38 MAP kinase (p38MAPK) and IL-4, while preventing induction of RS memory IgE responses. Others previously reported that CD4+ T cells and IL-4 were required for human IgE responses and that p38MAPK is associated with IL-4. We hypothesize that subP, previously shown to suppress murine memory IgE responses, will prevent induction of human RS memory IgE responses. MethodsPBMC were obtained from ragweed sensitized humans (n=4-6) and CD4+IL-4+ and CD8+CD60+IL-4+ T cell numbers determined ± incubation with PMA/ionophore. The effect of subP ± PMA/ionophore on these cells, on CD4+p38MAPK+ T cells, and on RS memory IgE responses were determined (flow cytometry, ELISA). PBMC were obtained from ragweed sensitized humans (n=4-6) and CD4+IL-4+ and CD8+CD60+IL-4+ T cell numbers determined ± incubation with PMA/ionophore. The effect of subP ± PMA/ionophore on these cells, on CD4+p38MAPK+ T cells, and on RS memory IgE responses were determined (flow cytometry, ELISA). ResultsCD4+IL-4+ T cells were 5% of CD4+ T cells; CD8+CD60+IL4+ T cells were >99% of CD8+CD60+ T cells. SubP did not suppress CD4+IL-4+ or CD8+CD60+IL-4+ T cells. Nevertheless, subP suppressed T cell p38MAPK (30-70%) and induction of RS memory IgE responses. As reported, minocycline strongly suppressed IL-4, T cell p38MAPK and RS memory IgE responses. CD4+IL-4+ T cells were 5% of CD4+ T cells; CD8+CD60+IL4+ T cells were >99% of CD8+CD60+ T cells. SubP did not suppress CD4+IL-4+ or CD8+CD60+IL-4+ T cells. Nevertheless, subP suppressed T cell p38MAPK (30-70%) and induction of RS memory IgE responses. As reported, minocycline strongly suppressed IL-4, T cell p38MAPK and RS memory IgE responses. ConclusionsSubP and minocycline appear to suppress RS memory IgE responses by different mechanisms. SubP did not suppress IL-4 but minocycline did. Both suppressed IgE responses. It is possible that subP suppresses events occurring downstream of IL-4. Further, it is possible that subP suppresses other cytokines required for memory IgE responses. SubP and minocycline appear to suppress RS memory IgE responses by different mechanisms. SubP did not suppress IL-4 but minocycline did. Both suppressed IgE responses. It is possible that subP suppresses events occurring downstream of IL-4. Further, it is possible that subP suppresses other cytokines required for memory IgE responses.

Peak TMA Specific IgG Responses May Predict the Likelihood of TMA Exposed Workers Developing TMA Specific IgE Responses

Workplace exposure to Trimellitic Anhydride (TMA) can elicit specific IgG and IgE antibody responses leading to occupational asthma (OA). An immuno-surveillance program to identify and remove workers with TMA-specific serum IgE, who are at risk for OA, has been previously developed. This purpose of this study was to determine whether the kinetics of specific antibody responses can differentiate workers who only develop TMA specific IgG from those that progress to specific IgE.

Allergen Specific IgE Response Is Similar in HIV-1 Seropositive and Seronegative Adults: Implications for HAART Induced Th2 to Th1 Switching

FEBRUARY 2015 AB8 Abstracts S A T U R D A Y 24 Allergen Specific IgE Response Is Similar in HIV-1 Seropositive and Seronegative Adults: Implications for HAART Induced Th2 to Th1 Switching Mili Shum, MD, Ashlei Mathew, MD, Maja Nowakowski, PhD, Hamid Moallem, MD, Tamar A. Smith-Norowitz, PhD, Helen G. Durkin, PhD, Rauno O. Joks, MD, FAAAAI; State University of New York Downstate Medical Center, Brooklyn, NY, Center for Allergy and Asthma Research, State University of New York Downstate Medical Center, Brooklyn, NY, Center for Allergy and Asthma Research at SUNY Downstate Medical Center, Brooklyn, NY, SUNY Downstate Medical Center, Brooklyn, NY, Center for Allergy and Asthma Research, SUNY Downstate, Brooklyn, NY. RATIONALE: Advanced HIV disease has been associated with Th2 mediated IgE responses, including IgE anti-HIV, and decreased atopy. The effect of HAART (highly active antiretroviral therapy) on Th2 mediated allergic IgE responses has not been determined. METHODS: Retrospective chart review was performed for adults seen in Allergy clinic at University Hospital of Brooklyn during 7/2000 to 5/2014. Subjects included HIV-1 patients on HAART and a control group consisting of HIV-1 seronegative patients (age and sex matched with a clinical visit in the samemonth). Total and allergen specific serum IgE was determined by ImmunoCAP assay; Skin prick test (SPT, Dermapik) for aeroallergens was performed using the Dermapik method. A mixed linear model was constructed for each dependent variable (IgE, no. of positive allergy results). Fixed factors were HIV status and gender; age was introduced as a linear covariate; matched pair ID was introduced as a random factor. RESULTS: Seventy-four subjects were analyzed with equal number of subjects in each group. HIV-1 seropositive subjects on HAART and controls had similar total serum IgE of 90.95 IU/ml and 144.54 IU/ml respectively (p50.23) and similar numbers of positive allergen specific IgE responses of 3.34 and 4.06, respectively (p50.28). CONCLUSIONS: These findings suggest there is limited effect of HAART on Th2 to Th1 switching.

Impact of Exposure Level and Duration on Reducing TMA Specific IgE Responses in Workers over Time

Trimellitic Acid anhydride (TMA) immunosurveillance programs in the workplace are essential for preventing occupational disease. The purpose of this study was to determine the effect of magnitude and duration of TMA exposure on persistence of TMA-specific IgE responses.

Association Between PTPN22 Polymorphisms and IgE Responses to Staphylococcal Superantigens in Chronic Urticaria.

Protein tyrosine phosphatase-22 (PTPN22) gene encodes lymphoid-specific tyrosine phosphatase (Lyp), an inhibitor of T cell activation. A polymorphism of the PTPN22 gene has been found to be associated with chronic urticaria (CU). We investigated the associations between PTPN22 gene polymorphisms and CU characteristics, including serum specific IgE antibodies response to toxic shock syndrome toxin-1 (TSST-1) and staphylococcal enterotoxin A (SEA). CU patients (n=409) and normal healthy controls (n=388) were enrolled in the present study. Serum specific IgE to TSST-1 and SEA were measured by ImmunoCAP®. Five PTPN22 single nucleotide polymorphisms, -1123G>C, 1858C>T, 13145A>G, 14943C>T, and 20628A>G, were genotyped. There were no significant differences in genotype or haplotype frequencies of these polymorphisms between the 2 groups. CU patients carrying the GG genotype at 20628A>G (P=0.035) or haplotype 3 [GGG] (P=0.047) had a significantly higher prevalence of serum specific IgE to TSST-1 compared to non-carriers. Similarly, CT/TT genotype at 14943C>T had a significantly higher prevalence of serum specific IgE to SEA (P=0.045). The findings suggest that the PTPN22 gene polymorphisms at 20628A>G and 14943C>T may enhance serum specific IgE responses to TSST-1 and SEA, which may contribute to CU pathogenesis.

Systemic and localized seminal plasma hypersensitivity patients exhibit divergent immunologic characteristics

Systemic and localized seminal plasma hypersensitivity patients exhibit divergent immunologic characteristics

Parental hay fever reinforces IgE to pollen as pre-clinical biomarker of hay fever in childhood.

An early IgE response to grass or birch pollen can anticipate seasonal allergic rhinitis to pollen later in life or remain clinically silent. To identify risk factors early in life that allow discriminating pathogenic from non-pathogenic IgE responses and contribute to the development of seasonal allergic rhinitis to grass pollen. The German Multicentre Allergy Study examined a birth cohort born in 1990. A questionnaire was yearly administered and blood samples collected at age 1,2,3,5,6,7,10,13 yr. The definition of the primary outcome grass- and birch-pollen-related seasonal allergic rhinitis (SARg, SARb) was based on nasal symptoms in June/July and April, respectively. Serum IgE antibodies to Phleum pratense and Betula verrucosae extracts were monitored with immune-enzymatic singleplex assays. Of the 820 examined children, 177 and 148 developed SARg and SARb, respectively. Among healthy children aged 3 or more years, IgE to grass pollen was the strongest risk factor of SARg (OR 10.39, 95%CI 6.1-17.6, p < 0.001), while parental hay fever was the only risk factor in early childhood independently associated with future SARg (1 parent: OR 2.56, 95%CI 1.4-4.5, p < 0.001; 2 parents: OR 4.17, 95%CI 1.7-10.1) and SARb (1 parent OR: 5.21, 95%CI 2.20-12.4, p < 0.001; 2 parents: OR 8.02, 95%CI 2.0-32.9, p < 0.001). Parental hay fever was associated with an increase of the concentration of pollen-specific IgE in seropositive subjects, after the age of 6 and was also a hallmark of molecularly more complex specific IgE responses to grass or birch pollen at age 6 or older. Parental hay fever and specific IgE to grass and/or birch pollen are strong pre-clinical determinants and potentially good predictors of seasonal allergic rhinitis.

Neonatal vaccination with plasmid DNA encoding Cyn d 1 effectively prevents allergic responses in mice.

Allergic rhinitis is one of the most common atopic disorders in children. There is no available method to prevent airway sensitization in newborns except allergen avoidance. Recombinant DNA plasmids encoding allergens have been proven to activate Th1 but attenuate Th2-deviated allergic responses in adult animal studies. However, their preventive effects are not presumptive in neonates because of their immature immune function. The aim of this study was to examine the potential preventive effect of a DNA vaccine encoding grass pollen allergen Cyn d 1 on allergic reaction to grass pollen in neonatal mice. Recombinant plasmid Cyn d 1 (pCyn d 1) vaccine was constructed by insertion of Cyn d 1 cDNA into the vector pcDNA3. Neonatal BALB/c mice received the vaccine once on the 3rd day of life or a second dose 2 days later. Control mice received PBS only. Mice were sensitized twice with recombinant Cyn d 1 and alum beginning at 7 weeks of age. Serum antibody responses and cytokine profiles of spleen cells were examined. Neonatal injection with pCyn d 1 vaccine resulted in IgG2a responses and production of interferon gamma in spleen cells. Vaccination with pCyn d 1 also reduced specific IgE responses and spleen cell secretion of IL-4. This study shows the prophylactic effects of DNA vaccine encoding Bermuda grass pollen allergen Cyn d 1 on specific IgE responses in neonatal mice.

Chimeras of Bet v 1 and Api g 1 reveal heterogeneous IgE responses in patients with birch pollen allergy

BackgroundCharacterization of IgE-binding epitopes of allergens and determination of their patient-specific relevance is crucial for the diagnosis and treatment of allergy.ObjectiveWe sought to assess the contribution of specific surface areas of the major birch pollen allergen Bet v 1.0101 to binding IgE of individual patients.MethodsFour distinct areas of Bet v 1 representing in total 81% of its surface were grafted onto the scaffold of its homolog, Api g 1.0101, to yield the chimeras Api-Bet-1 to Api-Bet-4. The chimeras were expressed in Escherichia coli and purified. IgE binding of 64 sera from Bet v 1–sensitized subjects with birch pollen allergy was determined by using direct ELISA. Specificity was assessed by means of inhibition ELISA.ResultsrApi g 1.0101, Api-Bet-1, Api-Bet-2, Api-Bet-3, and Api-Bet-4 bound IgE from 44%, 89%, 80%, 78%, and 48% of the patients, respectively. By comparing the amount of IgE binding to the chimeras and to rApi g 1.0101, 81%, 70%, 75%, and 45% of the patients showed significantly enhanced IgE binding to Api-Bet-1, Api-Bet-2, Api-Bet-3, and Api-Bet-4, respectively. The minority (8%) of the sera revealed enhanced IgE binding exclusively to a single chimera, whereas 31% showed increased IgE binding to all 4 chimeras compared with rApi g 1.0101. The chimeras inhibited up to 70% of IgE binding to rBet v 1.0101, confirming the specific IgE recognition of the grafted regions.ConclusionThe Bet v 1–specific IgE response is polyclonal, and epitopes are spread across the entire Bet v 1 surface. Furthermore, the IgE recognition profile of Bet v 1 is highly patient specific.

Novel Mechanisms Of Immune Modulation By Alpha-1-Antitrypsin

S U N D A Y 484 CD4+ and CD8+ T Cells Of Allergic Humans Express Increased Phosphorylated p38 MAP Kinase (p38MAPK), Substance P Suppresses T Cell Expression Of p38MAPK and Memory IgE Responses Bryan McCarthy, BS, Jonathan I. Silverberg, MD, PhD, MPH, Seto M. Chice, MS, Ankuri Desai, BS, Dr. Tamar A. Smith-Norowitz, PhD, Mark Stewart, MD, PhD, Dr. Rauno Joks, MD, Helen G. Durkin, PhD; Center for Allergy and Asthma Research at SUNY Downstate, Brooklyn, NY, Center for Allergy and Asthma Research, State University of New York Downstate Medical Center, Brooklyn, NY. RATIONALE: Magnetic/electrical stimulation of IgE+ human/rat left TPO cortex increases serum/blood substance P (2 hr) and CD4+/CD8+ T cell numbers (4 hr), while suppressing IgE responses (4 days). Thymus supplied T cells to blood because thymectomy or cutting of spinal cord at T2 (thymic innervation level) abrogated their appearance. Substance P suppresses specific murine IgE responses in vivo/vitro, and a relationship between p38MAPK and IL-4 has been reported. The effect of substance P on p38MAPK expression by human lymphocyte subsets and memory IgE responses has not been studied. METHODS: Distributions of p38MAPK+ lymphocytes (CD4+,CD8+,CD19+,CD16+) in PBMC obtained from ragweed sensitized IgE+ humans were determined6 15-30 min incubation with PMA6 substance P (flow cytometry). In addition, PBMC were cultured for 0-12 days 6 ragweed antigen 6 substance P and IgE levels in supernatants determined (ELISA). RESULTS: Before PMA stimulation, virtually no p38MAPK+ T cells (CD4+, CD8+), B or NK cells were detected in PBMC (<5%). After PMA, virtually all T cells, and CD4+ T cells which had been purified from PBMC, were p38MAPK+ (90-98%), with no change in p38MAPK+ B or NK cells.When PBMCor purified CD4+ T cells were incubatedwith PMA + substance P, p38MAPK+ CD4+ and CD8+ T cell numbers were suppressed (50-75%) When PBMC were cultured with ragweed antigen, peak IgE responses were induced on day 8; inclusion of substance P in culture prevented induction of these responses on all days. CONCLUSIONS: Taken together, our results indicate that brain can suppress IgE responses by releasing substance P.

The impact of structural integrity and route of administration on the antibody specificity against three cow's milk allergens - a study in Brown Norway rats.

BackgroundCharacterisation of the specific antibody response, including the epitope binding pattern, is an essential task for understanding the molecular mechanisms of food allergy. Examination of antibody formation in a controlled environment requires animal models. The purpose of this study was to examine the amount and types of antibodies raised against three cow’s milk allergens; β-lactoglobulin (BLG), α-lactalbumin (ALA) and β-casein upon oral or intraperitoneal (i.p.) administration. A special focus was given to the relative amount of antibodies raised against linear versus conformational epitopes.MethodsSpecific antibodies were raised in Brown Norway (BN) rats. BN rats were dosed either (1) i.p. with the purified native cow’s milk allergens or (2) orally with skimmed milk powder (SMP) alone or together with gluten, without the use of adjuvants. The allergens were denatured by reduction and alkylation, resulting in unfolding of the primary structure and a consequential loss of conformational epitopes. The specific IgG1 and IgE responses were analysed against both the native and denatured form of the three cow’s milk allergens, thus allowing examination of the relative amount of linear versus conformational epitopes.ResultsThe inherent capacity to induce specific IgG1 and IgE antibodies were rather similar upon i.p. administration for the three cow’s milk allergens, with BLG = ALA > β-casein. Larger differences were found between the allergens upon oral administration, with BLG > ALA > β-casein. Co-administration of SMP and gluten had a great impact on the specific antibody response, resulting in a significant reduced amount of antibodies. Together results indicated that most antibodies were raised against conformational epitopes irrespectively of the administration route, though the relative proportions between linear and conformational epitopes differed remarkably between the allergens.ConclusionsThis study showed that the three-dimensional (3D) structure has a significant impact on the antibodies raised for both systemic and orally administered allergens. A remarkable difference in the antibody binding patterns against linear and conformational epitope was seen between the allergens, indicating that the structural characteristics of proteins may heavily affect the induced antibody response.

Protecting effect of Enterococcus faecium on intestinal epithelial structure in Balb/c mice immunized via intra-peritoneal way by β-lactoglobulin

Protecting effect of Enterococcus faecium on intestinal epithelial structure in Balb/c mice immunized via intra-peritoneal way by β-lactoglobulin

Mites and allergy.

Allergic diseases triggered by mite allergens include allergic rhinoconjunctivitis, asthma, atopic dermatitis and other skin diseases. Since the early discovery of the allergenic role of mites of the genus Dermatophagoides in the mid 1960s, numerous species have been described as the source of allergens capable of sensitizing and inducing allergic symptoms in sensitized and genetically predisposed individuals. The main sources of allergens in house dust worldwide are the fecal pellets of the mite species D. pteronyssinus, D. farinae, Euroglyphus maynei and the storage mites Blomia tropicalis, Lepidoglyphus destructor and Tyropahgus putrescentiae. Group 1 and 2 allergens are major house dust mite allergens. The main allergens in storage mites include fatty acid-binding proteins, tropomyosin and paramyosin homologues, apolipophorin-like proteins, α-tubulins and others, such as group 2, 5 and 7 allergens. Cross-reactivity is an important and common immunological feature among mites. Currently, purified native or recombinant allergens, epitope mapping, proteomic approaches and T cell proliferation techniques are being used to assess cross-reactivity. Mites contain potent enzymes capable of degrading a wide range of substrates. Most mite allergens are enzymes. Advances in genomics and molecular biology will improve our ability to understand the genetics of specific IgE responses to mites. Mite allergen avoidance and immunotherapy are the only two allergen-specific ways to treat mite-induced respiratory and cutaneous diseases.

IgE versus IgG4 epitopes of the peanut allergen Ara h 1 in patients with severe allergy

BackgroundDevelopment and maintenance of tolerance to food allergens appears to be associated with alterations in antigen specific IgE and IgG4 responses. Previous studies have focused only on comparing IgE and IgG4 linear epitope recognition patterns but take no account of conformational epitopes. ObjectiveThe aim of this study was to compare Ara h 1-specific IgE and IgG4 epitope recognition patterns in patients with severe peanut allergy, applying a method allowing for identification of both linear and conformational epitopes. MethodsPolyclonal sera from three individual patients, suffering from severe allergic reaction to peanuts, including anaphylaxis, were used to analyse the IgE and IgG4 epitope recognition patterns of the major peanut allergen Ara h 1. Epitope identification was conducted by competitive immuno-screening of a phage-displayed random heptamer peptide library. Resulting epitope-mimicking sequences were aligned for identification of consensus sequences and localised on the surface of the Ara h 1 molecule by a computer-based algorithm. ResultsAll epitope-mimicking sequences identified were found to correspond to conformational epitopes. Each individual patient had his/her own distinct IgE as well as IgG4 epitope recognition profile, though some important IgE epitopes were common to all patients. In general the IgG4 epitope pattern was more heterogeneous than the IgE pattern, did not coincide with IgE epitopes and had a lower affinity than IgE. ConclusionsThis study demonstrated the usefulness of the phage-display technology in distinguishing between the epitope pattern of IgE and IgG4, giving detailed information on fine specificity and affinity. Competitive immuno-screening of phage-display random peptide libraries could be a future valuable tool to study the balance and dynamics of the IgE and IgG4 epitope recognition repertoire and provide a diagnostic tool giving information on the associated allergic phenotype.

Immunogenic activity of the fish tapewormPterobothrium heteracanthum(Trypanorhyncha: Pterobothriidae) in BALB/c mice

The aim of this study was to verify the immunogenicity of Pterobothrium heteracanthum (Cestoda: Trypanorhyncha) crude protein extract (PH-CPE) in BALB/c mice. The parasites were obtained from Micropogonias furnieri (Osteichthyes: Sciaenidae). Groups of six mice were each immunized with 10, 50 or 100 μg of PH-CPE, on days 0 and 35. Both specific IgG and IgE responses were developed after immunization. The immunoblot assay revealed that specific IgG recognizes PH-CPE proteins with two molecular weight ranges, 60-75 and 30-40kDa, and that IgE recognizes larger proteins over 120kDa. This appears to be the first report on the immunogenicity of metacestodes within the Pterobothriidae and that PH-CPE is a potential inducer of a specific IgE response.

Early life IgE responses in children living in the tropics: A prospective analysis

There are few birth cohort studies analyzing IgE sensitization in the tropics. We aimed to describe the evolution of total IgE and specific IgE responses to house-dust mite (HDM) allergens and Ascaris in a birth cohort (Risk Factors for Asthma and Allergy in the Tropics, FRAAT), analyzing their relationships with wheezing. Total and specific IgE were measured by ImmunoCap in mothers and children at four different time points (S1-S4) between 0 and 42 months. Parasite infection was evaluated by stool examination. Maternal total IgE (aOR: 2.43, 95% CI: 1.09-5.43; p = 0.03) and socio-demographic factors were associated with high cord blood (CB) total IgE. High CB total IgE was positively associated with higher Blomia tropicalis and Ascaris-specific IgE values during lifetime, but protected from recurrent wheezing (aOR: 0.26, 95% CI: 0.08-0.88, p = 0.03). Prevalence rates of IgE sensitization were high; at around 3 yr old, they were 33.3, 18.6, and 26.5% for B. tropicalis, Dermatophagoides pteronyssinus, and Ascaris, respectively. Indicators of unhygienic conditions were risk factors for HDM and Ascaris sensitization in children. A weak statistical association between B. tropicalis-specific IgE and ever wheezing was found (aOR: 1.47 95% CI: 1.00-2.28, p = 0.05). In a socioeconomically deprived community from the tropics, sensitization to HDM allergens was very frequent at early life, especially to B. tropicalis. In contrast to expected according to the hygiene hypothesis, unhygienic/poverty conditions were risk factors for allergen sensitization. High CB total IgE levels were a risk factor for allergen sensitization but protected from recurrent wheezing.

IgE-Mediated Immune Responses and Airway Detection of Aspergillus and Candida in Adult Cystic Fibrosis

The recovery of Aspergillus and Candida from the respiratory secretions of patients with cystic fibrosis (CF) is common. Their relationship to the development of allergic sensitization and effect on lung function has not been established. Improved techniques to detect these organisms are needed to increase knowledge of these effects. A 2-year prospective observational cohort study was performed. Fifty-five adult patients with CF had sputum monitored for Aspergillus by culture and real-time polymerase chain reaction and Candida by CHROMagar and carbon assimilation profile (API/ID 32C). Skin prick tests and ImmunoCAP IgEs to a panel of common and fungal allergens were performed. Lung function and pulmonary exacerbation rates were monitored over 2 years. Sixty-nine percent of patient sputum samples showed chronic colonization with Candida and 60% showed colonization with Aspergillus. There was no association between the recovery of either organism and the presence of specific IgE responses. There was no difference in lung function decline for patients with Aspergillus or Candida colonization compared with those without (FEV₁ percent predicted, P = .41 and P = .90, respectively; FVC % predicted, P = .87 and P = .37, respectively). However, there was a significantly greater decline in FEV1 and increase in IV antibiotic days for those sensitized to Aspergillus (FEV₁ decline, P = .03; IV antibiotics days, P = .03). Allergic sensitization is not associated with recovery of Candida or Aspergillus from the sputum of patients with CF. Aspergillus but not Candida sensitization is associated with greater lung function decline and pulmonary exacerbations.

Significance of Ara h 2 in clinical reactivity and effect of cooking methods on allergenicity

BackgroundThe prevalence and clinical severity of peanut allergy vary between Western countries and Asia. It has been suggested that cooking methods are responsible for this discrepancy. ObjectivesTo evaluate the specific IgE responses to major peanut allergens in peanut allergic Korean children and to examine the influence of different cooking methods on peanut proteins. MethodsRaw peanut protein extracts were immunolabeled with serum samples from 42 children with a level of peanut specific IgE of 15 kUA/L or higher to detect specific binding to Ara h 1, Ara h 2, and Ara h 3. Clinical severity scores were assessed on a scale of 0 to 5. Protein extracts from boiled, roasted, fried, and pickled peanuts were analyzed by sodium dodecyl sulfate–polyacrylamide gel electrophoresis and immunoblotting with pooled serum samples from 7 patients. ResultsMost patients' serum samples reacted with Ara h 1 (76.2%) and Ara h 3 (78.6%) from raw peanuts, whereas only 53.0% of patients had specific IgE against Ara h 2. IgE binding to Ara h 2 was more prevalent in patients with more severe reaction than in those with mild reactions. IgE binding to Ara h 2 was increased by roasting, but there was significantly less IgE binding after vinegar treatment. ConclusionOur results suggest that Ara h 2 is an important allergen to predict clinical symptoms but less prevalent in Korean children than in Western children. This finding may be attributed in part to different cooking methods and dietary habits among regions.

Sublingual Immunotherapy Induces Regulatory Function of IL-10-Expressing CD4+CD25+Foxp3+T Cells of Cervical Lymph Nodes in Murine Allergic Rhinitis Model

Sublingual immunotherapy (SLIT) has been considered to be a painless and efficacious therapeutic treatment of allergic rhinitis which is known as type I allergy of nasal mucosa. Nevertheless, its mechanisms need to be further investigated. In this study, we constructed an effective murine model of sublingual immunotherapy in allergic rhinitis, in which mice were sublingually administered with ovalbumin (OVA) followed by intraperitoneal sensitization and nasal challenge of OVA. Sublingually treated mice showed significantly decreased specific IgE responses as well as suppressed Th2 immune responses. Sublingual administration of OVA did not alter the frequency of CD4+CD25+ regulatory T cells (Tregs), but led to upregulation of Foxp3- and IL-10-specific mRNAs in the Tregs of cervical lymph nodes (CLN), which strongly suppressed Th2 cytokine production from CD4+CD25− effector T cells in vitro. Furthermore, sublingual administration of plasmids encoding the lymphoid chemokines CCL19 and CCL21-Ser DNA together with OVA suppressed allergic responses. These results suggest that IL-10-expressing CD4+CD25+Foxp3+ Tregs in CLN are involved in the suppression of allergic responses and that CCL19/CCL21 may contribute to it in mice that received SLIT.