Background: DNA vaccines encoding allergens have been developed to prevent or to treat specific IgE responses. Objective: To evaluate the potential preventive and therapeutic effect of DNA vaccines encoding Cyn d 1 alone or combined with different adjuvants on specific allergies. Methods: Recombinant plasmid Cyn d 1 (pCyn d 1) was constructed by insertion of Cyn d 1 cDNA into the vector pcDNA3. BALB/c mice were injected with pCyn d 1 alone or plus adjuvants such as bupivacaine, bestatin, liposome, or CpG. Control mice were treated with pcDNA3 or PBS. They were boosted 3 weeks later and then sensitized twice with recombinant Cyn d 1 and alum. Their serum antibody responses and cytokine profiles of spleen cells were studied. Adoptive transfer of spleen cells of pCyn d 1-vaccinated mice was also performed. Results: Vaccination of mice with pCyn d 1 induced Th1 responses characterized by IgG2a responses and spleen cell secretion of interferon-γ. Vaccination with pCyn d 1 not only prevented the induction of specific IgE responses but also suppressed ongoing IgE responses. The mice receiving untreated, CD4+- or CD8+-depleted spleen cells from pCyn d 1-vaccinated mice all had suppression of IgE responses. Conclusion: This study confirms the prophylactic and therapeutic effects of DNA vaccines encoding Bermuda grass pollen allergen Cyn d 1 on specific IgE responses. Both CD4+ and CD8+ T cells are crucial for the immunomodulatory effect of pCyn d 1 on specific IgE responses.
PMID: 22286313 [PubMed - as supplied by publisher]
Higher Frequencies of CD161 Circulating T Lymphocytes in Allergic Rhinitis Patients Compared to Healthy Donors.
Int Arch Allergy Immunol. 2012 Jan 25;158(2):151-156
Authors: Poggi A, Canevali P, Contatore M, Ciprandi G
Abstract
Background:Th17 is a subset of T-helper lymphocytes that produce proinflammatory cytokines, mainly IL-17. Serum IL-17 is increased in allergic patients and relates to clinical severity. Recently, it has been reported that CD161 is a highly upregulated gene in Th17 clones and all IL-17-producing cells are contained in CD161(+) T cells. This study aimed at comparing the frequency of peripheral CD161(+) T cells in patients with allergic rhinitis (AR) and in healthy controls and at relating CD161 expression with symptom severity. Methods: Forty-four patients with AR and 29 healthy non-allergic subjects were evaluated. CD161 expression was evaluated on CD3(+), CD4(+) and CD8(+) cells by double immunofluorescence staining and fluorescence activated cell sorter analysis. Symptom severity was assessed by the Visual Analogue Scale. Results: Allergic patients showed a significantly higher frequency of CD3(+)CD161(+), CD4(+)CD161(+) and CD8(+)CD161(+) cells than healthy non-allergic subjects (p < 0.0001). Moreover, the expression of CD161 cells was significantly related to clinical severity. Conclusions: This study provides evidence that a higher frequency of CD161(+) T cells is present in the peripheral blood of AR patients.
PMID: 22286340 [PubMed - as supplied by publisher]
Expression and Characterization of Natural-Like Recombinant Der p 2 for Sublingual Immunotherapy.
Int Arch Allergy Immunol. 2012 Jan 25;158(2):157-167
Authors: Bordas-Le Floch V, Bussières L, Airouche S, Lautrette A, Bouley J, Berjont N, Horiot S, Huet A, Jain K, Lemoine P, Chabre H, Batard T, Mascarell L, Baron-Bodo V, Tourdot S, Nony E, Moingeon P
Abstract
Background: Recombinant allergens with a native conformation represent an alternative to natural extracts for immunotherapy and diagnostic purposes. Methods: We produced the Der p 2 mite allergen in Pichia pastoris and Escherichia coli. After purification by cation exchange chromatography, recombinant molecules were compared to their natural counterpart based upon structural (disulfide bonds, secondary structure, thermal stability) and immunological properties (antibody reactivity, basophil and T cell activation, tolerance induction in a murine sublingual immunotherapy model). Results: The Der p 2.0101 isoform was confirmed to be prevalent in Dermatophagoides pteronyssinus extracts. It was then produced as a secreted molecule in P. pastoris or refolded from E. coli inclusion bodies. The yeast-expressed rDer p 2 molecule exhibits a natural-like disulfide bridge distribution and secondary structure, whereas the E. coli-derived rDer p 2 presents some heterogeneity in cysteine bonds and a lower stability following thermal stress. The two recombinant as well as natural Der p 2 molecules exhibit comparable IgE recognition and activate basophil and CD4+ T cells. Sublingual immunotherapy of nDer p 2- sensitized mice using either one of the rDer p 2 molecules efficiently decreases airway hyperresponsiveness as well as Th2 responses. Conclusions: Natural and recombinant Der p 2 molecules produced in P. pastoris and E. coli exhibit comparable immunological properties despite distinct structural features. Natural-like cysteine pairing is a critical parameter to identify stable, well-folded and homogenous proteins appropriate for immunotherapy and diagnostic purposes.
PMID: 22286395 [PubMed - as supplied by publisher]
Prevalence of Atopy and Allergic Diseases in Korean Children: Associations with a Farming Environment and Rural Lifestyle.
Int Arch Allergy Immunol. 2012 Jan 25;158(2):168-174
Authors: Lee SY, Kwon JW, Seo JH, Song YH, Kim BJ, Yu J, Park KS, Kim H, Kim EJ, Lee JS, Hong SJ
Abstract
Background: The results of recent studies suggest that factors in rural environments may protect against the development of allergic diseases, but the underlying mechanisms are not well understood. The aim of this study was to investigate the prevalence of allergic diseases, to establish if this prevalence is influenced by migration from rural to urban areas and to identify environmental risk factors associated with these diseases. Methods: A cross-sectional study of children aged 9-12 years from a rural village, a rural town and an urban city in Korea was conducted. Demographic and disease-related information was obtained via a detailed questionnaire, and skin prick tests were performed. Results: There were significant differences in lifestyle and environmental factors between children from the rural village, the rural town and the urban children. The prevalence of allergic diseases and atopy was higher in urban children. A lower prevalence of allergic diseases and atopy was associated with farming parents, contact with farm animals during pregnancy, owning pets or a stable, breast-feeding and having older siblings. A comparison of rural village and rural town children revealed no evidence of an association of allergic diseases and atopy with farming parents, contact with farm animals during pregnancy or owning a stable. On the other hand, having older siblings and antibiotic use during infancy were significantly associated with allergic diseases and atopy in these children. Conclusions: Protective factors associated with a farming environment and/or rural lifestyle may influence the prevalence of allergic diseases and atopy in Korean children.
PMID: 22286539 [PubMed - as supplied by publisher]
The Impact of Cigarette Smoking on Asthma: A Population-Based International Cohort Study.
Int Arch Allergy Immunol. 2012 Jan 26;158(2):175-183
Authors: Cerveri I, Cazzoletti L, Corsico AG, Marcon A, Niniano R, Grosso A, Ronzoni V, Accordini S, Janson C, Pin I, Siroux V, de Marco R
Abstract
Background: The prevalence rates of smoking in subjects with asthma have frequently been reported as similar to those in the general population; however, available data are not up-to-date. There is only limited and somewhat conflicting information on the long-term effects of smoking on health outcomes among population-based cohorts of subjects with asthma. We aimed to investigate changes in smoking habits and their effects on forced expiratory volume in 1 s (FEV(1)) in subjects with asthma in comparison with the rest of the population, focusing on the healthy smoker effect. Methods: We studied 9,092 subjects without asthma and 1,045 with asthma at baseline who participated in both the European Community Respiratory Health Survey I (20-44 years old in 1991-1993) and II (1999-2002). Results: At follow-up, smoking was significantly less frequent among subjects with asthma than in the rest of the population (26 vs. 31%; p < 0.001). Subjects with asthma who were already ex-smokers at the beginning of the follow-up in the 1990s had the highest mean asthma score (number of reported asthma-like symptoms, range 0-5), probably as a result of the healthy smoker effect (2.80 vs. 2.44 in never smokers, 2.19 in quitters and 2.24 in smokers; p < 0.001). The influence of smoking on FEV(1) decline did not depend on asthma status. Smokers had the highest proportion of subjects with chronic cough/phlegm (p < 0.01). Conclusion: One out of 4 subjects with asthma continues smoking and reports significantly more chronic cough and phlegm than never smokers and ex-smokers. This stresses the importance of smoking cessation in all patients with asthma, even in those with less severe asthma.
PMID: 22286571 [PubMed - as supplied by publisher]
The Loss of Smell in Persistent Allergic Rhinitis Is Improved by Levocetirizine due to Reduction of Nasal Inflammation but Not Nasal Congestion (the CIRANO Study).
Int Arch Allergy Immunol. 2012 Jan 26;158(2):184-190
Authors: Guilemany JM, García-Piñero A, Alobid I, Centellas S, Mariño FS, Valero A, Bernal-Sprekelsen M, Picado C, Mullol J
Abstract
Background: Persistent allergic rhinitis (PER) has a moderate impact on the sense of smell, but no controlled study has reported the effect of antihistamines on the loss of smell in patients with PER. Methods: Patients with PER and subjective loss of the sense of smell (n = 27) were included in this pilot randomised, double-blind, placebo-controlled study. Nasal symptoms, nasal endoscopy, skin prick test, acoustic rhinometry, peak nasal inspiratory flow, nasal nitric oxide (nNO), and olfactometry (Barcelona Smell Test-24; BAST-24) were performed and evaluated in all PER patients at baseline and after 7 and 30 days of treatment with levocetirizine 5 mg or placebo. Results: The study population was randomized into two homogeneous groups: levocetirizine (n = 14) and placebo groups (n = 13). The evolution of symptoms reflected the therapeutic effect of levocetirizine treatment on rhinorrhea, nasal itching, eye itching, sneezing, and the total symptoms score after 7 and 30 days. Significant improvement in loss of smell by a visual analog scale (VAS) was observed after 7 days of levocetirizine treatment (7.2 ± 4.3; p < 0.05) compared to placebo (-9.4 ± 6.2). Improvement in smell identification by BAST-24 was strongly correlated (r = 0.72; p < 0.05) with smell improvement by VAS after 30 days. After 7 days of treatment with levocetirizine, the nNO values decreased (-494 ± 188) compared to placebo (155 ± 284 ppb; p < 0.05). Conclusions: The CIRANO study suggests that levocetirizine is effective on PER symptoms, including a transient improvement in loss of smell, and that this improvement concurs more with reduction of nasal inflammation than of nasal patency.
PMID: 22286639 [PubMed - as supplied by publisher]
Effects of Bepotastine and Fexofenadine on Histamine-Induced Flare, Wheal and Itch.
Int Arch Allergy Immunol. 2012 Jan 26;158(2):191-195
Authors: Tanizaki H, Ikoma A, Fukuoka M, Miyachi Y, Kabashima K
Abstract
Background: Urticaria is mainly caused by mast cell-derived histamine through the histamine H(1) receptor. Antihistamines are occasionally used on demand upon a recurrence of urticaria; therefore, rapidly acting agents should be explored. The onset of action is assumed to depend on time to maximum concentration (T(max)), but the speed of action needs to be evaluated not only through blood concentration analysis but also by measuring in vivo effectiveness. Methods: In this study, we chose two representative second-generation antihistamines (bepotastine and fexofenadine) with relatively short T(max) values and evaluated their effects on histamine-induced skin responses using both visual and laser Doppler imaging scales. Results: Suppression of histamine-induced flare and itch was observed 3 and 6 h after administration of both antihistamines. Attenuation of itch was seen 30 min after the administration of each drug and thereafter until 6 h. In addition, bepotastine suppressed flare formation after only 30 min following application. Conclusion: These results suggest that antihistamines suppress histamine-induced itch and flare, followed by wheal formation, and that bepotastine suppresses skin symptoms sooner after administration than fexofenadine does, which is relatively consistent with the T(max) results.
PMID: 22286689 [PubMed - as supplied by publisher]
Susceptibility to Vaccinia Virus Infection and Spread in Mice Is Determined by Age at Infection, Allergen Sensitization and Mast Cell Status.
Int Arch Allergy Immunol. 2012 Jan 26;158(2):196-205
Authors: Domenico J, Lucas JJ, Fujita M, Gelfand EW
Abstract
Background: Patients, especially young children, with atopic dermatitis are at an increased risk of developing eczema vaccinatum, a severe reaction to the smallpox vaccine, either through direct vaccination or indirect contact with a person recently vaccinated. Methods: Using a mouse model of infection, the severity of vaccinia-induced lesions was assessed from their appearance and viral DNA content. The response to vaccinia inoculation was assessed in young and adult mice, allergen-sensitized mice, and in mast cell-deficient mice. Results: Young age, sensitization to an allergen prior to infection, and a mast cell deficit, accomplished by using mast cell-deficient mice, resulted in more severe viral lesions at the site of inoculation, according to lesion appearance and viral DNA content. All three factors combined demonstrated maximal susceptibility, characterized by the severity of primary lesions and the development of secondary (satellite) lesions, as occurs in eczema vaccinatum in humans. Resistance to the appearance of satellite lesions could be restored by adoptive transfer of bone marrow-derived mast cells from either wild-type or cathelicidin-related antimicrobial peptide-deficient mice. Primary lesions were more severe following the latter transfer, indicating that cathelicidin-related antimicrobial peptide does contribute to the protective activity of mast cells against infection. Conclusions: The combination of young age, allergen sensitization and a mast cell deficit resulted in the most severe lesions, including satellite lesions. Understanding the factors determining the relative resistance/sensitivity to vaccinia virus will aid in the development of strategies for preventing and treating adverse reactions which can occur after smallpox vaccination.
PMID: 22286752 [PubMed - as supplied by publisher]
Multiorgan Infiltration by CD8+ T Cells and 1p;16p Translocation in a Patient with Hypogammaglobulinemia and a Reduced Number of B Cells.
Int Arch Allergy Immunol. 2012 Jan 26;158(2):206-210
Authors: Vultaggio A, Matucci A, D’Elios MM, Andreucci E, Giglio S, Annunziato F, Zupo S, Maggi E
Abstract
Common variable immunodeficiency (CVID) disorders are the most common form of clinically significant primary immunodeficiencies found in adults. There is now clear evidence that CVID includes a group of clinically and genetically heterogenous conditions. In addition to recurrent infections, some patients are highly prone to granulomatous lesions. Rarely, CVID may be characterized by an increased number of circulating CD8+ T cells with tissue infiltration. We report a unique case of CVID associated with a sarcoidosis-like disease and polyclonal CD8+ T cell expansion with multiple tissue infiltration occurring in a subject with the chromosome translocation t(1;16). No sequence variant in TACI, APRIL, BAFF, ICOS or BTK genes was discovered. Cytometric analysis showed that the chemokine receptors expressed on peripheral and tissue CD8+ T cells are responsible for the tissue homing of the cells. Moreover, CD8+ T cells produced high amounts of IFN-γ, but not IL-4 and IL-17, with regular expression of the transcription factor Vav1. Genes coding for IL-32 and FRAP1, both involved in the regulation of memory T cell differentiation, are located in the translocation breakpoint. This suggests that a chromosomal abnormality plays a role in the clinical features of this phenotypic variant of CVID.
PMID: 22286841 [PubMed - as supplied by publisher]
Basophil Activation Test in Allergy: Time for an Update?
Int Arch Allergy Immunol. 2012 Jan 20;158(2):99-114
Authors: Chirumbolo S
Abstract
A wide range of reported evidence in the literature has shown that the quantification of basophil activation by flow cytometry (basophil activation test, BAT) has proven to be a useful tool for the assessment of immediate-type responses to allergens mediated by IgE or other mechanisms in allergic patients. The usefulness of BAT in anaphylactic adverse reactions, late-onset allergy and immunotherapy follow-up has also been demonstrated. To date, most BAT studies reported in the literature involved the capture of basophils only with a fluorochrome-labeled anti-IgE antibody and application of CD63 upregulation in order to evaluate the basophil response to allergens. Many issues need to be addressed, such as optimizing the analytical performance of the test, checking preanalytical conditions, the selection of the flow cytometry best gating protocol, the introduction of new algorithms and parameters, the search for new activation markers and the introduction of anti-IgE controls. BAT is certainly a useful technique, also for isolated cases of hypersensitivity to various other compounds and drugs, and an update of its application is certainly an interesting topic to expand the debate on allergy diagnosis.
PMID: 22269476 [PubMed - as supplied by publisher]
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