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PKU-related dysgammaglobulinaemia: the effect of diet therapy on IgE and allergic sensitization.

The effect of diet on the development of immunoallergic signs and symptoms in children with phenylketonuria (PKU) was evaluated. Immunological indices of 58 children with PKU treated with diets were compared to the immunological indices of 58 healthy (non-PKU) children. In the PKU group, 39 children had been placed on diet therapy within the first month of life; 19 children had been placed on diet therapy after 6 months of age. Total circulating lymphocytes; CD3+, CD4+, CD8+ circulating lymphocytes; and serum IgA, IgM, IgG and total IgE levels were measured for each child. Skin prick tests were performed for common inhalant and food allergens. Every 3 months over the 2-year period of this study, the signs and symptoms of eczema, allergic rhinitis and asthma were recorded. The PKU group had lower IgG levels (p = 0.004) and higher total IgE levels (p = 0.0001) than the control group. Significantly lower IgE levels were found in children started on diet therapy within the first month of life compared with those started on diet therapy after 6 months of age (p = 0.0001). Allergic sensitization was significantly more frequent in the PKU group (24/58 vs 13/58, z = 2.00, p < 0.05), but no significant difference in the incidence of eczema and allergic rhinitis was found. Asthma was less frequent in the PKU group than in the control group (5/58 vs 14/58, z = 2.09, p < 0.05). Thus, diet appeared to prevent the development of immunoallergic signs and symptoms.

Adolescent↗

Usefulness of specific immunotherapy in patients with atopic dermatitis and allergic sensitization to house dust mites: a multi-centre, randomized, dose-response study.

BACKGROUND: The effect of specific immunotherapy (SIT) on eczema in atopic dermatitis is not known. Therefore, a multi-centre, randomized dose-response trial, double-blind with respect to the efficacy of a biologically standardized depot house dust mite preparation was performed. METHODS: Eighty-nine adults with a chronic course of atopic dermatitis, SCORAD >or=40 and allergic sensitization to house dust mites [CAP-FEIA >or=3] were included, of whom 51 completed the study. Subcutaneous SIT with a house dust mite preparation (Dermatophagoides pteronyssinus/D. farinae) applying maintenance doses of 20, 2,000 and 20,000 SQ-U in weekly intervals for 1 year. The main outcome measures addressed the change of the SCORAD as average of the values after 9 and 12 months of SIT in comparison with the value at baseline. RESULTS: The SCORAD declined in the three dose groups in a dose-dependent manner (P = 0.0368, Jonckheere-Terpstra test) and was significantly lower in the two high-dose groups (2,000, 20,000 SQ-U) compared with the low-dose group of 20 SQ-U (P = 0.0379, U-test) after 1 year of SIT. The use of topical corticosteroids was significantly reduced with higher doses (P = 0.0007, Mantel-Haenszel chi-square test). CONCLUSIONS: Allergen-SIT for 1 year with a house dust mite preparation is able to improve the eczema in patients with atopic dermatitis who are sensitized to house dust mite allergens and reduces the need for topical corticosteroids. SIT may be valuable in the treatment of this chronic skin disease.

Adolescent↗

Allergic sensitization owing to 'second-hand' cat exposure in schools.

BACKGROUND: Environmental allergen loads play an important role in triggering symptoms in atopic individuals. While a number of previous studies have shown that cat allergens (Fel d 1) can be found in school dust samples, no study has provided evidence that public places contribute to increased atopic sensitization rates in children. METHODS: We employed data collected in a health survey of school children living in Germany in order to examine the association between the proportion of class- and schoolmates reporting cat contact and sensitization rates in children. RESULTS: Among 1893 children, 8.7% were sensitized to cats. Those sensitized were 5-7 times more likely to have received an asthma diagnosis or to have reported wheezing. Pupils without regular contact with cats were twice as likely to test positive for major cat allergen when the proportion of schoolmates with cat contact was high. No such relation was observed amongst children reporting regular cat contact. CONCLUSIONS: Our study suggests that allergens in school environments contribute to allergic sensitization and atopic diseases such as asthma. Thus, methods to reduce the allergen load in classrooms should be considered.

Adolescent↗

The effect of diesel exhaust particles (DEP) and carbon black (CB) on thiol changes in pulmonary ovalbumin allergic sensitized Brown Norway rats.

Brown Norway rats were exposed by intratracheal instillation of saline, carbon black (CB), or diesel exhaust particles (DEP) (5 mg/kg) on day 1, followed by exposure to ovalbumin (OVA, 90 mg/m(3)) or saline for 30 minutes on days 1, 8, 15, and 29. Animals were sacrificed on day 30. The DEP, CB, or OVA exposure alone did not result in abnormal levels of inflammatory cells, lactate dehydrogenase (LDH), or total protein in the lavage fluid. In combined OVA-DEP or OVA-CB exposure, however, these markers were significantly increased. The adjuvant effect of CB and DEP on OVA sensitization was evidenced by the marked increases in serum OVA-specific IgG (5.6-fold) and IgE (3.5-4 fold) levels, and the increase in interleukin-4 (IL-4) mRNA levels in lung tissue. The OVA exposure markedly reduced glutathione (GSH) levels in both cell types. In combined DEP-OVA exposure, the level of GSH in lymphocytes was further decreased, indicating a possible interactive effect between DEP and OVA exposures. These results show that both DEP and CB augmented OVA-induced allergic sensitization, and that particle composition of DEP may not be a critical factor for the adjuvant effect. OVA exposure causes significant depletion of intracellular GSH in lymphocytes, which may play a key role in OVA-mediated immune responses.

Animals↗

Prenatal allergic sensitization to helminth antigens in offspring of parasite-infected mothers.

Total and filaria-specific immunoglobulin E (IgE) levels were studied in cord blood from infants born in Madras, India, where filariasis and intestinal helminth infections are highly endemic. Increased total IgE levels were observed in 82% of 57 cord sera tested (geometric mean 12.6 ng/ml; range 1-1,900 ng/ml). 33 of these sera also contained IgE antibodies specific for filarial antigens as determined by solid-phase radioimmunoassay. Comparison of ratios of filaria-specific IgE to total IgE in paired maternal and cord sera suggested that cord blood IgE was derived from the fetus in most cases and not from transplacental antibody transfer. Our results suggest that prenatal allergic sensitization to helminth parasites occurs in the tropics. Such sensitization may contribute to the heterogeneity in host immune response and disease expression noted in filariasis and other helminth infections.

Antigens↗

Allergic sensitization and clinical reactions to latex, food and pollen in adult patients.

BACKGROUND: Many latex-allergic patients are sensitized to one or more foods. Patients allergic to tree and/or grass pollens are also often sensitized to plant-derived foods. Atopy, defined in most studies as sensitivity to an aeroallergen, is a risk factor for latex allergy. The relative importance of pollen sensitivity, a sign of atopy, as a risk factor for food allergy in latex-allergic patients has not, however, been examined. OBJECTIVE: To investigate the relationship between pollen sensitivity and sensitivity to food in latex-allergic patients. METHODS: Forty-four latex-allergic patients (Groups 1 and 2), 24 of whom were also allergic to tree and/or grass pollen (Group 1) and 25 pollinosis patients who were not allergic to latex (Group 3) were studied. We obtained a history of reactions to food and skin tested them with 12 fresh-frozen fruits. RESULTS: All 12 foods induced a skin test reaction in at least one patient in each of the three Groups. There were, however, twice as many positive skin test reactions to food in patients with pollinosis, whether or not they were allergic to latex, as there were in patients allergic to latex but not to pollen. Latex-allergic patients were most likely to have a positive skin test and a history of a reaction to avocado or banana whereas patients with pollinosis only were most likely to have a positive skin test and a history of a reaction to apple, peach or celery. CONCLUSIONS: These results suggest that concomitant allergy to pollen is an important risk factor in determining which plant-derived foods sensitize latex-allergic patients.

Adolescent↗

Effects of SO2 exposure on allergic sensitization in the guinea pig.

The effect of sulfur dioxide (SO2) exposure on local bronchial sensitization to inhaled antigen was studied in the guinea pig. Exposure to SO2 (0.1 to 16.6 ppm) was performed in a 20 L exposure chamber for 8 hours on 5 consecutive days, while temperature, moisture, and concentration of SO2 were monitored and kept constant. SO2 concentrations were measured hourly by Schiff's reaction. On the last 3 days, SO2 exposure was followed by inhalation of nebulized ovalbumin (OA) for 45 minutes. One week later, specific bronchial provocation with inhaled OA (0.1%) followed by plethysmographic measurements of airway obstruction were performed every 2 days during a 2-week period. Specific antibodies against OA were measured in serum and bronchoalveolar fluid by a direct enzyme immunoassay. The SO2-exposed group (N = 17) demonstrated 67% to 100% positive bronchial reactions to inhaled OA, depending on the concentration of SO2, whereas the control group without previous SO2 exposure (N = 14) demonstrated bronchial reactions in only one animal (7%: p less than 0.05). The degree of bronchial obstruction was significantly higher in the exposed group, compared to the control group, for all SO2 concentrations (p less than 0.05). OA-specific antibodies in serum and bronchoalveolar fluid increased in SO2-exposed groups significantly, compared to the control group (p less than 0.05). It is concluded from these results that exposure to SO2 in low and medium concentrations can facilitate local allergic sensitization in the guinea pig.

Aerosols↗

Glycosylation-inhibiting factor from human T cell hybridomas constructed from peripheral blood lymphocytes of a bee venom-sensitive allergic patient.

Human T cell hybridomas, which constitutively secrete glycosylation inhibiting factor (GIF), were constructed from PBL of an allergic individual who was sensitive to honey bee venom. PBMC of the patient were stimulated with either denatured or cyanogen bromide-treated bee venom phospholipase A2 (PLA2), and Ag-activated cells were propagated by IL-2 in the presence of human recombinant lipocortin I. T cells obtained in the cultures were fused with a HAT-sensitive mutant of the human lymphoblastoid cell line CEM. Approximately one-third of hybridoma clones constitutively secreted GIF. The GIF-producing hybridomas were CD3+ and bore TCR-alpha beta. GIF formed by unstimulated hybridomas lacked affinity for bee venom PLA2. Upon cross-linking of CD3, however, a majority of the GIF-producing hybridomas formed IgE-binding factors and GIF, the latter of which had affinity for bee venom PLA2. Both nonspecific GIF and Ag-binding GIF from the hybridomas bound to an immunosorbent coupled with the anti-lipomodulin mAb 141-B9. Using an affinity-purified GIF as an immunogen, we established mouse B cell hybridomas that secreted monoclonal anti-human GIF. In order to characterize human nonspecific GIF, one of the GIF-producing hybridomas was adapted to a serum-free medium, and culture supernatant was fractionated by DEAE-Sepharose column chromatography and by gel filtration. The majority of nonspecific GIF in the culture supernatant was recovered from DEAE-Sepharose by elution of the column with 10 mM Tris-HCl buffer, pH 8.0, containing 50 mM NaCl. Affinity-purification of GIF in the DEAE Sepharose fraction by using anti-GIF-coupled Affigel, and analysis of the purified GIF by SDS-PAGE revealed that human GIF is a single polypeptide chain of 14 to 15 kDa. Gel filtration of both crude and affinity-purified GIF preparations confirmed the molecular size of the cytokine.

Antibodies, Monoclonal↗

Allergic sensitization to a non-bisphenol A epoxy of the cycloaliphatic class.

This is the first report of sensitization to a cycloaliphatic epoxy. Allergic contact dermatitis occurred in an electron microscopist after exposure to the cycloaliphatic epoxy, vinyl cyclohexene diepoxide. Cycloaliphatic epoxies are not based on the diglycidyl ether of bisphenol A (DGEBA), presently the epoxy of greatest commercial usage. However, non-DGEBA epoxies are finding new applications in the semiconductor and aerospace industries and will likely gain in importance as a cause of occupational allergic dermatitis. Latex or polyvinyl chloride gloves did not protect the reported patient from percutaneous absorption and elicitation of allergic dermatitis.

Cyclohexanes↗

House dust mite Dermatophagoides farinae augments proinflammatory mediator productions and accessory function of alveolar macrophages: implications for allergic sensitization and inflammation.

In this study, we examine the effects of Dermatophagoides farinae (Der f), a major source of airborne allergens, on alveolar macrophages (AMs), and we also test its contribution to allergic responses in mice. Der f activated NF-kappaB of AMs and, unlike OVA or LPS stimulation, up-regulated IL-6, TNF-alpha, and NO. In addition, it down-regulated antioxidants, but affected neither the expression nor production of IL-12. Der f-stimulated AMs expressed enhanced levels of costimulatory B7 molecules, supported T cell proliferation, and promoted Th2 cell development. The enhanced accessory function was suppressed by blockade mAbs to B7.2, IL-6, and TNF-alpha and by N-monomethyl-L-arginine, an NO synthase inhibitor, and N-acetylcysteine, a thiol antioxidant, whereas it was augmented by (+/-)-S-nitroso-N-acetylpenicillamine, an NO donor. Arg-Gly-Asp-Ser peptide and neo-glycoproteins galactose-BSA and mannose-BSA inhibited the Der f-induced IL-6 and TNF-alpha productions and enhanced accessory function of AMs. Der f was more potent than OVA for inducing pulmonary eosinophilic inflammation, NO, and serum allergen-specific IgG1 Ab production in mice. AMs from Der f-challenged mice expressed enhanced levels of B7 and augmented T cell proliferation ex vivo. In Der f-challenged mice, respiratory syncytial virus infection (5 x 10(5) pfu; 3 days before Der f instillation) augmented Der f-specific Ab production, whereas dexamethasone (50 mg/kg; 1 h before Der f instillation) diminished the allergic airway inflammation and Ab response. We conclude that AMs are sensitive targets for Der f and that the Der f-induced proinflammatory responses may represent an important mechanism in mediating the development of allergic sensitization and inflammation.

Adjuvants, Immunologic↗

Biology of common beta receptor-signaling cytokines: IL-3, IL-5, and GM-CSF.

IL-3, IL-5, and GM-CSF are related hematopoietic cytoines that are important for allergic inflammation. The receptors for human IL-5, IL-3, and GM-CSF are members of the hematopoietin receptor superfamily and are comprised of a cytokine-specific alpha chain and the common beta chain that is shared among these cytokines for signaling. Each of these cytokines contributes to the differentiation and function of leukocyte subpopulations and have clinical importance in protective immunity and in the pathophysiology of a spectrum of immunologic diseases that are as diverse as allergy and asthma, pulmonary alveolar proteinosis, neurodegenerative diseases, and malignancies. Delineating the biology of these cytokines is enabling the development of new strategies for diagnosing and treating these diseases and modulating immune responses.

Animals↗

Hyperpolarized 3He MRI in asthma measurements of regional ventilation following allergic sensitization and challenge in mice--preliminary results.

RATIONALE AND OBJECTIVES: Quantitative regional measurement of physiological parameters of lung may improve both early detection of asthma and its response to treatment by elucidating the characteristics of airway obstruction. Recent emergence of hyperpolarized helium-3 magnetic resonance imaging as a sensitive pulmonary imaging tool has shown great potential in capturing important structural and functional aspects of normal and diseased lungs. The objective of this study was to investigate regional ventilation changes in the mouse lung following allergen sensitization and challenge. MATERIALS AND METHODS: A murine model of allergic airway inflammation was created in mice following allergen challenge using Af and IgE-mediated asthma. The creation of model was verified using pulmonary function test and histology. Regional fractional ventilation was then measured in the animals using hyperpolarized 3He MRI on a pixel-by-pixel basis with a planar resolution of 0.24 mm. The sensitized and healthy animals were then compared statistically to assess the potential sensitivity of this technique in detection of such pulmonary abnormalities. RESULTS: In this work, we have demonstrated for the first time the quantitative measurement of regional ventilation in normal and asthmatic mice. Results of this study show significant changes in regional ventilation in murine model of allergic airway sensitization compared with that in normal control animals. CONCLUSION: Further development of this technique can potentially serve as a quantitative marker to investigate the physiology of allergen-induced airway hyperresponsiveness and to assist in disease treatment and prevention.

Animals↗

IL-10- and IL-12-independent down-regulation of allergic sensitization by stimulation of CD40 signaling.

Interaction between CD154 (CD40 ligand) on activated T lymphocytes and its receptor CD40 has been shown to be critically involved in the generation of cell-mediated as well as humoral immunity. CD40 triggering activates dendritic cells (DC), enhances their cytokine production, up-regulates the expression of costimulatory molecules, and induces their maturation. It is unknown how stimulation of CD40 during sensitization to an airborne allergen may affect the outcome of allergic airway inflammation. We took advantage of a mouse model of allergic asthma and a stimulatory mAb to CD40 (FGK45) to study the effects of CD40-mediated DC activation on sensitization to OVA and subsequent development of OVA-induced airway inflammation. Agonistic anti-CD40 mAb (FGK45) injected during sensitization with OVA abrogated the development of allergic airway inflammation upon repeated airway challenges with OVA. Inhibition of bronchial eosinophilia corresponded with reduced Th2 cytokine production and was independent of IL-12, as evidenced by a similar down-regulatory effect of anti-CD40 mAb in IL-12 p40-deficient mice. In addition, FGK45 equally down-regulated allergic airway inflammation in IL-10-deficient mice, indicating an IL-10-independent mechanism of action of FGK45. In conclusion, our results show that CD40 signaling during sensitization shifts the immune response away from Th2 cytokine production and suppresses allergic airway inflammation in an IL-12- and IL-10-independent way, presumably resulting from enhanced DC activation during sensitization.

Animals↗

Characterization of exposure to low levels of viable Penicillium chrysogenum conidia and allergic sensitization induced by a protease allergen extract from viable P. Chrysogenum conidia in mice.

BACKGROUND: Previous evidence by our laboratory has shown that mice inoculated with viable Penicillium Chrysogenum conidia or spores at levels comparable to those found in contaminated buildings induced spore antigen-specific allergic responses. We proposed that mice exposed to low levels of viable P. Chrysogenum conidia would not develop allergic symptoms. We also hypothesized that the symptoms induced by high numbers of conidia were the result of sensitization to allergens released by the conidia. METHODS: C57BL/6 and BALB/c mice were exposed to 1 x 10(2) viable P. Chrysogenum conidia by intranasal instillation weekly for a period of 11 weeks. C57BL/6 mice were also sensitized to a viable P. Chrysogenum conidia protease extract by intraperitoneal injections for a period of 6 weeks followed by intranasal challenge with protease extract, viable, or nonviable P. Chrysogenum conidia for 2 weeks. RESULTS: C57BL/6 mice inoculated with low numbers of conidia developed no significant lung inflammation or increased serum immunoglobulins. Mice sensitized to the protease extract and challenged with both protease extract and viable conidia produced significant increases in serum IgE and IgG1. Mice sensitized to and challenged with the protease extract developed significant eosinophilia and mucus hyperproduction as determined by bronchoalveolar lavage and histopathological examination of lung tissue. CONCLUSIONS: Mice did not develop allergic symptoms in response to challenge with low levels of P. Chrysogenum conidia. Protease allergens from viable conidia induced specific allergic responses in mice, indicating the importance of P. Chrysogenum conidia in allergic sensitization to the organism.

Allergens↗

Allergic sensitization increases airway reactivity in guinea pigs with respiratory syncytial virus bronchiolitis.

BACKGROUND: Respiratory syncytial virus (RSV) causes acute bronchiolitis in children and has been implicated in the pathogenesis of recurrent wheezing and asthma. However, few children exposed to RSV experience acute bronchiolitis or its sequelae, suggesting a subgroup of susceptible children. An allergic diathesis may predispose children to subsequent airway disease. OBJECTIVE: This study was carried out to determine whether a preexisting allergic state, induced by repeated inhalational exposures to ovalbumin, potentiates nonspecific airway responsiveness to acetylcholine and increases airway inflammation during acute RSV bronchiolitis in guinea pigs. METHODS: Forty guinea pigs were randomized into four groups: nonsensitized, noninfected (ovalbumin-, RSV-); sensitized, noninfected (ovalbumin+, RSV-); nonsensitized, infected (ovalbumin-, RSV+); sensitized, infected (ovalbumin+, RSV+). Depending on grouping, animals were exposed to either repeated aerosols of ovalbumin or saline solution and were subsequently inoculated with either human RSV or uninfected culture medium. Six days after inoculation, animals underwent acetylcholine challenge, and lung specimens were prepared for histologic scoring of airway inflammation. RESULTS: Maximal increases in pulmonary resistance (centimeters of water per milliliter per second) to acetylcholine were greater for RSV alone (12.4 +/- 3.9) and ovalbumin alone (13.7 +/- 3.9) compared with controls (4.3 +/- 1.1), but significantly greater increases occurred in ovalbumin+, RSV+ animals (34.0 +/- 11.0). These ovalbumin+, RSV+ animals demonstrated the combined histologic changes noted with RSV alone and ovalbumin alone including airway epithelial necrosis, mononuclear and granulocyte infiltrates, airway wall edema, hyperplasia of bronchus-associated lymphoid tissue, and goblet cell metaplasia. CONCLUSION: Prior allergic sensitization potentiates the physiologic and structural changes induced by acute RSV bronchiolitis. These results suggest that an allergic diathesis may increase the severity of RSV infections in children.

Acetylcholine↗

Relationship between number of allergic sensitizations and immunity impairment: anything new in immunotherapy for allergies and vaccines planning?

To 106 14-56 year-old allergic people (30 monosensitized, 24 sensitized to 2 pollens, 52 polysensitized) we have evaluated the Global Immune Competence Status (GICS). That's a compound score, made of ten parameters, six regarding cell-mediated immunity (WBC/mmc, Gr/mmc, Ly/mmc, Ly CD3+/mmc, Ly CD4+/mmc, CD4/CD8 Ratio), four regarding nutritional status and humoral immunity (Tot. Protein mg/dl, Albumin mg/dl, Gammaglobulins mg/dl, IgG mg/dl). Each parameter is brought on a grid including 4 worth scores worsening from 4 to 1, related to different ranges of values; this way quickly leads to characterize type and grade of immune deficiency. So doing we found that in 30 monosensitized people 27 (90%) show a complete immune competence, while just 3 people (10%) have impaired GICS: in these 1 (3%) regards cell-mediated immunity, while 2 (7%) regard humoral immunity. In 24 patients sensitized to 2 allergenes, 18 (75%) showed complete immune competence, while 6 (25%) a GICS impairment regarding cell-mediated immunity. In leaving 52 polysensitized patients, 30 people showed complete immune competence (58%), while 20 (38%) showed a GICS impairment regarding cell-mediated immunity and 2 (4%) impaired humoral immunity. This work shows that the higher the number of sensitizations is, the stronger the cell-mediated immunity impairment in allergic people become.

Adolescent↗

Cytokines and regulation of allergic sensitization to chemicals.

Sensitization to chemicals and the elicitation of allergic reactions results from the stimulation of specific immune responses. Adaptive immunity is orchestrated by cytokines, a family of inducible glycoproteins that influence in many ways the behaviour of, and interaction between, cells which mediate immune and inflammatory responses. In this article the role of cytokines in the development of cutaneous immune responses to chemical allergens and in directing the quality of immune responses provoked by such materials is discussed.

Animals↗

Skin reactivity and specific IgE levels in the evaluation of allergic sensitivity to common allergens for epidemiological purposes.

An investigation was conducted to test the validity of the skin-prick test (SPT) with eleven common allergens (Lofarma series proposed by Italian National Research Council for epidemiological studies) as a method for predicting the presence of specific antibodies in serum. The relationship between SPT, evaluated by two different methods (MWD = mean weal diameter, AHWR = allergen histamine weal ratio), and specific IgE levels (RAST) has been investigated in 101 patients tested consecutively for suspected allergic disease. Sensitivity, specificity and overall efficiency were assessed for different criteria of SPT positivity (greater than or equal to 4 mm or greater than or equal to 5 mm using MWD; ++ or using AHWR). For pollens and moulds, a weal diameter greater than or equal to 5 mm gave better results than 4 mm, whereas for mites a MWD greater than or equal to 4 mm showed a better sensitivity and overall efficiency than 5 mm. Danders showed low sensitivity when either 5 or 4 mm criterion was considered. AHWR evaluation gave no better results, except for animal danders. Correlation coefficients between weal size and RAST class showed a good relationship for mites and pollens using both methods of SPT evaluation; a moderate relationship was observed with MWD criterion for moulds and with AHWR for danders. We conclude that a weal diameter greater than or equal to 5 mm can be assumed to to predict RAST positivity for pollens and moulds, and for mites, a weal greater than or equal to 4 mm can be a more accurate criterion.(ABSTRACT TRUNCATED AT 250 WORDS)

Allergens↗