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Biomedical subjects

H Løwenstein

Publications and source records attributed to H Løwenstein.

At least 19 recordsLinked to original sources

Modified T-cell activation pattern during specific immunotherapy (SIT) in cat-allergic patients.

OBJECTIVE: The aim of the study was to analyse early effects of specific immunotherapy (SIT) on immune functions in cat-allergic patients. METHODS: Immunological responses of peripheral blood mononuclear cells from eight cat-allergic patients were analysed before and after SIT in comparison with 11 nonallergic controls. Cells were stimulated in vitro with either bacterial superantigen, mitogen, or cat allergen. Production of IL-12 and TH1/TH2 cytokines was analysed by ELISA and lymphocyte subset distribution was assessed by flow-cytometry. RESULTS: We found a significantly reduced secretion of IL-12 (P < 0.05) from cells of allergic individuals compared with the controls. This finding was associated with significantly lower IFN-gamma production after stimulation with allergen (P < 0.05) that did not increase during SIT. However, no significant differences were seen after stimulation with mitogen indicating an allergen specific IFN-gamma secretion response in allergic individuals. Prior to SIT IL-5 production was significantly higher in cells of allergic donors stimulated with allergen < 0.005 or mitogen (< 0.05). After reaching the maintenance dose for SIT, allergen-induced IL-5 production returned to normal levels, whereas it remained elevated after stimulation with mitogen. These changes were associated with a reduced frequency of CD45 RO T cells following SIT. CONCLUSION: These results suggest that SIT exerts early effects on allergen-specific T-cell responses with selective inhibition of the up-regulated TH2 immune response.

Allergens

Specific immunotherapy with Dermatophagoides pteronyssinus and D. farinae results in decreased bronchial hyperreactivity.

To evaluate the tolerability and efficacy of specific immunotherapy with mite extracts, we performed a double-blind, placebo-controlled immunotherapy study in 30 patients with proven allergy to mite allergens. The specific immunotherapy with standardized extracts of Dermatophagoides pteronyssinus and D. farinae by a clustered rush protocol was well tolerated. After 1 year of treatment, the actively treated group showed a significant improvement compared to their starting value as well as to the placebo-treated patients with regard to skin prick test, conjunctival provocation test, and subjective rhinitis score. The subjective asthma score and bronchial hyperreactivity, measured by the methacholine provocation test, was improved in comparison to the starting value, but not to the placebo group, after 12 months. However, a further, open comparison of the placebo- and verum-treated groups at 18 months revealed a significant reduction. The drug intake was not increased in the verum-treated group. Exposure to mite levels was constant throughout this time period, as revealed by antigen measurement. We conclude that specific immunotherapy in perennial, mite-allergen-induced asthma may reduce not only immediate, IgE-mediated symptoms but, after a rather long time period of 12-18 months, also the inflammatory component of bronchial asthma, thus leading to a reduction of unspecific hyperreactivity.

Adult

Comparison of concentrations of Cry j 1 and Cry j 2 in diploid and triploid Japanese cedar (Cryptomeria japonica) pollen extracts.

Japanese cedar (Cryptomeria japonica) possibilities has been a serious allergic disease in Japan. There are two kinds of Japanese cedar trees; the popular one is diploid, the less popular is triploid. These trees are not very different morphologically. However, the relative allergenicity of their pollens is unknown, although both major allergens, Cry j 1 and Cry j 22, have been purified and cloned from the diploid line. Triploid trees are sterile and the allergenicity of their pollen may differ. Using Japanese-cedar-allergic patient sera, we compared the concentration of these two major allergens in both kinds of pollen. Pollen collected from different years and regions was also studied. The results indicate that triploid tree pollen extract has lower concentrations of both major allergens; therefore, the pollen may be less allergenic.

Allergens

Immunotherapy with partially purified and standardized tree pollen extracts. IV. Results from long-term (6-year) follow-up.

The long-term effect of tree pollen extract immunotherapy was investigated 6 years after termination of the treatment. Subjective symptom evaluation of 36 patients 6 years after a 3-year period of immunotherapy showed that rhinitis and asthma symptoms remained at the improved level reached just after termination of the treatment. Some 86% of the rhinitis patients and 68% of the asthma patients maintained improvement. None of the rhinitis patients developed asthma in the study period. Skin prick tests reflected the outcome of the subjective symptom assessment. The skin sensitivity of the patients decreased significantly during immunotherapy, and the skin reactions 6 years after specific immunotherapy were still significantly lower than the pretreatment levels. Total IgE and birch-specific IgE levels were constant throughout the study period, and both the affinity and epitope specificity of the IgE antibodies of the patients were the same before, during, and 6 years after treatment. In conclusion, specific immunotherapy reduces symptoms in patients suffering from rhinitis and asthma, and the effect is maintained 6 years after termination of the treatment. Specific immunotherapy seems to prevent long-term development of asthma in rhinitis patients. IgE measurements do not reflect the overall status of the patients.

Allergens

Cow hair allergen (Bos d 2) content in house dust: correlation with sensitization in farmers with cow hair asthma.

Farmers (N = 45) suffering from occupational cow hair asthma were visited at home to evaluate the concentration of cow hair major allergen Bos d 2 in the house dust and to correlate these results with measures of avoidance, degree of sensitization, clinical symptoms, and lung function. Bos d 2 was determined by rocket immunoelectrophoresis. In dust of tiles and linoleum Bos d 2 was difficult to detect, whereas dust samples of carpets often contained high concentrations of the allergen (50-520 micrograms/g fine dust). Bos d 2 levels were significantly higher when barn and living quarters were in the same building. Concentrations of cow hair-specific IgE were correlated with concentrations of Bos d 2 in house dust samples. A concentration of 20-29 micrograms Bos d 2 per gram of house dust could be established as threshold value for relevant IgE sensitization. Avoiding the barn is not a sufficient avoidance measure for cow hair asthmatics if the partner continues cattle farming. Cessation of cattle farming and avoiding the former barn results in a marked reduction in Bos d 2 concentration in living quarters, a decreased degree of sensitization, and a reduced symptom score. Farmers with cow hair asthma should avoid cattle and thoroughly clean all carpets in the living quarters to avoid continuous cow allergen exposure.

Adult

X-ray and NMR structure of Bet v 1, the origin of birch pollen allergy.

The three-dimensional structure of the major birch pollen allergen, the 17,500 M(r) acidic protein Bet v 1 (from the birch, Betula verrucosa), is presented as determined both in the crystalline state by X-ray diffraction and in solution by nuclear magnetic resonance (NMR) spectroscopy. This is the first experimentally determined structure of a clinically important inhalant major allergen, estimated to cause allergy in 5-10 million individuals worldwide. The structure shows three regions on the molecular surface predicted to harbour cross-reactive B-cell epitopes which provide a structural basis for the allergic symptoms that birch pollen allergic patients show when they encounter pollens from related trees such as hazel, alder and hornbeam. The structure also shows an unusual feature, a 30 A-long forked cavity that penetrates the entire protein.

Allergens

[Different threshold concentrations for sensitization by cattle hair allergen Bos d 2 in atopic and non-atopic farmers].

Several threshold values for indoor allergens leading to IgE sensitization were proposed. Currently such values exists for allergens of house dust mite, cat, dog, and cockroach and cattle. A high sensitization is known as an important risk factor in the development of asthma. This study was undertaken to examine threshold values of major cow hair allergen Bos d 2 in the house dust of atopic and nonatopic cow hair asthmatic farmers. 45 patients with cow hair asthma were visited at their homes. House dust samples were taken from corridor, living room, and bedroom. The concentration of Bos d 2 was determined by means of rocket immunoelectrophoresis. Additionally, samples of venous blood were taken to demonstrate specific IgE towards cow epithelia by CAP-RAST. Five patients were excluded from further investigations because they have given up their cattle for less than 6 months. In 21 patients occurred typical atopic stigmata like infantil history of atopic eczema, hay fever or milk crust, while the other 19 subjects did not show an atopic diathesis. High sensitization towards cow epithelia (specific IgE > 0.7 kU/l in CAP-RAST) occurred significantly more often in atopics than in nonatopics. In atopic subjects the allergen concentrations leading to IgE sensitization amounted to 1-20 micrograms Bos d 2/g dust, whereas in nonatopics were found higher Bos d 2 threshold values (25-50 micrograms/g dust). The present study suggests that in nonatopic cow hair asthmatics high indoor Bos d 2 levels lead to IgE sensitization as well as the close contact to cattle.

Agricultural Workers' Diseases

Long-term follow-up of patients treated with a three-year course of cat or dog immunotherapy.

BACKGROUND: A 5-year follow-up study was conducted to investigate the duration of the effects of a 3-year course of immunotherapy with standardized cat or dog extracts in 32 children and adults with asthma caused by animal dander. METHODS: Thirty of the subjects could be reached with a questionnaire, 19 underwent bronchial allergen and histamine challenges, and four had only a histamine challenge. Specific IgE and IgG4 levels in serum were measured in those who underwent challenges. RESULTS: Almost all subjects (26 of 30) reported no change (17 subjects) or increased tolerance (9 subjects) on exposure to cats or dogs. In contrast, 17 of the 19 who underwent allergen challenges had increased allergen sensitivity compared with when therapy was stopped (p < 0.01), and the results were no longer significantly different from before therapy was started. Mean provocative concentration of histamine causing a 20% fall in peak expiratory flow was, however, still higher than before therapy in the cat immunotherapy group (p < 0.01) and had not changed significantly during the follow-up period. In the dog immunotherapy group there was no significant change during or after therapy. Specific IgG4 had decreased, and specific IgE in serum had remained low and was comparable to the levels measured at the end of the study period. CONCLUSIONS: Five years after stopping immunotherapy, objectively measured bronchial allergen sensitivity had increased and had approached pretreatment conditions. Asthma symptoms, according to patients' subjective evaluations, had continued to be mild in most patients, and bronchial histamine sensitivity had remained stable. These observations could reflect remaining effects of immunotherapy or the natural history of mild asthma.

Adult

Characterization of Chenopodiales (Amaranthus retroflexus, Chenopodium album, Kochia scoparia, Salsola pestifer) pollen allergens.

Pollen extracts of the four taxonomically related weeds, Amaranthus retroflexus (Ama r), Chenopodium album (Che a), Kochia scoparia (Koc s), and Salsola pestifer (S. kali) (Sal p), were characterized by various methods including crossed immunoelectrophoresis (CIE), crossed radioimmunoelectrophoresis (CRIE), and SDS-PAGE immunoblotting. The allergen profiles were determined by CRIE and SDS-PAGE IgE immunoblotting. CRIE detected from one to four important allergens, while SDS showed up to four bands that bound IgE from a number of patient sera. CRIE and SDS-PAGE immunoblotting did not recognize the same number of important allergens in the individual weeds, and the number of allergens detected by the two methods differed considerably, suggesting that IgE-binding epitopes may be denatured during SDS-PAGE. However, it was possible to correlate the identity of some of the important allergens detected by CRIE and SDS-PAGE immunoblotting in all four weeds.

Allergens

Predominance of the major allergen (Alt a I) in Alternaria sensitized patients.

Thirty-nine patients sensitized to Alternaria were evaluated using titrated skin-prick test (SPT), histamine release studies (HR), inhibition of RAST and immunoblotting studies. To determine the relevance of the major allergen, Alt a I, specific rabbit antibodies against Alt a I and Alt a B were used. The antibodies were preincubated at different concentrations: (i) with the Alternaria allergen dose required for maximum response in the HR assay (10 BU/ml) and (ii) with the Alternaria antigen coupled to RAST paper discs (1000 BU/disc). Dose dependent inhibition of histamine release (n = 30, mean = 80% +/- 4%, IC30 = 0.69 micrograms/ml) and of RAST (n = 7, IC30 = 4.4 micrograms/ml) was found in all patients sensitized to Alternaria as indicated by allergen induced HR. The greater the response to Alternaria in HR, the higher the antibody concentrations necessary for inhibition (P < 0.05). Immunoblot experiments (n = 25) using SDS-PAGE showed in all cases IgE- and IgG binding at approximately 28 kD, which is the size reported for the major allergen, Alt a I. In two cases, slight IgE binding at 45 and 66 kD was also found, while in two other patients, only IgE binding at 66 kD was seen. Our findings emphasize the major importance of Alt a I in patients sensitized to Alternaria.

Adolescent

Role of the major allergen (Fel d I) in patients sensitized to cat allergens.

Forty patients with a positive case history and specific serum IgE to cat allergens were evaluated using titrated skin prick test (SPT), histamine release studies (HR) and immunoblotting studies. To determine the relevance of the major allergen, a monospecific antibody to Fel d I was preincubated in different concentrations with the cat allergen dose required for maximum response in the HR assay (10 SQ/ml). Dose-dependent inhibition of histamine release (n = 30, x = 66% +/- 5% IC30 = 0.36 micrograms/ml) was found in all patients sensitized to cat allergens as shown by antigen-induced HR. The greater the HR response to the cat allergen extract the higher were the antibody concentrations necessary for inhibition (p < 0.05). Immunoblot experiments (n = 22) using SDS-PAGE demonstrated five different locations of IgE binding in 15 sera: 18, 35, 46, 54 and 66 kD. IgE binding at 18 kD was found in 14 patients. Anti-Fel d I possessed two strong bands at about 18 and 35 kD which are representative of the major allergen Fel d I. Our findings emphasize the major role of Fel d I in patients sensitized to cat allergens.

Adolescent