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Biomedical subjects

S Dreborg

Publications and source records attributed to S Dreborg.

At least 73 records · Page 4Linked to original sources

Detection of Chlorella-specific IgE in mould-sensitized children.

The content of IgE, specific to the unicellular green alga Chlorella sp., was analysed in sera from 46 atopic children sensitized to moulds, using radioallergosorbent test (RAST), immunoblotting and crossed immunoelectrophoresis/crossed radioimmunoelectrophoresis (CIE/CRIE). Chlorella-specific IgE was found in 23/46 sera by RAST, in 28/41 sera by immunoblotting and in 6/30 sera by CIE/CRIE. The Chlorella components most frequently binding IgE as analysed by gradient gel electrophoresis and immunoblotting were of molecular weights of approximately 13, 17, 19, 26 and 49 kD. Twenty-nine precipitating antigens, including seven IgE-binding precipitates were detected by CIE/CRIE. The study shows that low concentrations of specific IgE are formed to the green alga Chlorella in sera from atopic individuals sensitized to moulds.

Adolescent↗

Immunotherapy with monomethoxypolyethylene glycol modified allergens.

On the basis of the results of experiments in naive mice, i.e., in mice which had not been presensitized, it was anticipated that mPEG-modified allergens would suppress the specific IgE response in allergic humans. However, only minor or no suppression of IgE antibodies was induced on administration of mPEG conjugates in allergic patients with a longstanding IgE response. This observation was later confirmed in pre-sensitized animals. The mPEG-modified allergens can be synthesized in a reproducible manner. This makes mPEG-modified allergens suitable for production and quality control. There is indirect evidence, i.e., identification of IgE and IgG antibody stimulation against all identified allergens, that the relevant determinants are available for processing by the immune system. By contrast, the polymerization of allergens by formaldehyde or glutaraldehyde leads to ill-defined, cross-linked high molecular weight materials. As in the case of other modified allergens, mPEG-modified allergens have been developed primarily because of their lower allergenicity than the original allergen preparations. However, they also retain clinical efficacy of the same magnitude as that induced by unmodified allergen preparations, which is a prerequisite for clinical use. IT with mPEG-modified pollen allergen preparations has been proven to be as effective as IT with unmodified allergens, when these preparations are given in similar doses. Furthermore, a more pronounced beneficial effect can be obtained with higher doses of mPEG-modified allergen, without the risk of side effects which are often precipitated by unmodified allergens. Therefore, it seems reasonable to suggest that children and young adults with developing sensitivity to perennial allergens, and without chronic changes of the bronchial mucosa, are the most suitable candidates for IT with mPEG-modified allergen preparations. Mite asthma, which always includes bronchial inflammation and nonspecific hyperresponsiveness, represents a more complicated model. In mite asthmatics mPEG-modified mite allergen preparations were safer than the corresponding unmodified preparation. Although bronchial sensitivity to allergen and histamine did not change significantly in mite asthmatics during the observation time, it appears that IT with mPEG-modified mite allergen led to a decrease in the releasability of histamine from skin mast cells, as measured by SPT, to a similar degree as observed in pollinosis patients. Therefore, it may be inferred that the allergic component of asthma might be influenced by IT with mPEG allergens. As a consequence, before the start of IT, the degree of reversibility of pathophysiological changes in the bronchial wall should be considered.(ABSTRACT TRUNCATED AT 400 WORDS)

Allergens↗

Diagnosis of mold allergy by RAST and skin prick testing.

Sera from 33 patients with mold allergy proven by bronchial provocation were analyzed for specific IgE against six mold species comparing an improved Phadebas RAST with four other techniques. The new method was more sensitive and gave significantly higher IgE antibody concentrations for all tested molds except Cladosporium herbarum.

Adult↗

Specific IgE, IgG, and IgA antibody response to oral immunotherapy in birch pollinosis.

Thirty-nine patients with birch pollinosis participated in a double-blind, placebo-controlled trial of oral immunotherapy (OIT) for 18 months. They were treated with increasing doses of freeze-dried birch-pollen antigens for 16 months, reaching a cumulative dose of 280 x 10(6) biologic units. This is about 200 times more than the dose used in conventional subcutaneous immunotherapy (IT). In the placebo-treated group, but not in the actively treated group, there was a rise in postseasonal birch-specific IgE antibody levels. A significant decline in postseasonal values after 1 year of treatment was recorded in the actively treated, but not in the placebo-treated, group. Compared to the placebo treatment, there was a significant rise in birch-specific IgG antibodies in patients administered active treatment; however, the rise was less than that usually observed during subcutaneous IT. No significant change in birch-specific serum IgA was found in either group. The changes in IgE and IgG antibody levels demonstrate that OIT affects the immune system. This supports our recent findings that OIT demonstrates a beneficial effect in the treatment of birch pollinosis in adults. But, as with subcutaneous IT, there was no clear relationship between antibody response and clinical findings in the patients. The underlying mechanisms responsible for the relief of symptoms thus remain unknown.

Administration, Oral↗

The skin prick test in the diagnosis of atopic allergy.

The factors that influence the results of skin prick tests are reviewed. The concentration and composition of allergen preparations, the test technique used, and the prevalence of allergy in the population studied are emphasized.

Allergens↗

Hyposensitization in asthmatics with mPEG modified and unmodified house dust mite extract. I. Clinical effect evaluated by diary cards and a retrospective assessment.

Forty-six asthmatics with verified allergy to the house dust mite, D. pteronyssinus (Dp), participated in a double-blind study comparing the effect of 2 years' hyposensitization with two different Dp extracts. Two groups received either monomethoxypolyethylene glycol modified (mPEG) Dp extract or the corresponding non-modified extract, and a third group acted as controls receiving no injections. Medicine consumption, symptom scores, and peak expiratory flow (PEF) were recorded daily from September to December prior to and after 6 and 18 months of treatment. Changes were calculated choosing changes greater than or equal to 10% as relevant. In addition, patients were asked to give their direct assessment of the clinical effect at the end of the study. After 6 months, there was an improvement in symptoms + medication in 11/14 of Dp-treated, 6/17 of the mPEG-Dp group (P greater than 0.05) and 3/15 of openly treated controls. Few patients had changed in PEF. During the second year, several Dp-treated relapsed and some controls improved. At the end of the study the same improvement rate was seen in all groups. Similarly, the retrospective questionnaire data did not disclose any significant differences between groups after 2 years. In conclusion, hyposensitization with unmodified Dp extract seemed to have a favourable short-term effect on bronchial symptoms + medication in the majority of patients. When mainly on maintenance dose, the beneficial effect was reduced. The mPEG modification of the extract had reduced not only allergenicity but also the clinical effect of equal doses. Changes in medicine and symptom scores only partly correlated to retrospective assessment, thus stressing the problems in this kind of evaluation.

Animals↗

Hyposensitization in asthmatics with mPEG modified and unmodified house dust mite extract. II. Effect evaluated by challenges with allergen and histamine.

In a 2-year study, 46 asthmatics with verified allergy to the house dust mite D. pteronyssinus (Dp) were included either as controls (Ctls) or receiving hyposensitization (HS) with unmodified or monomethoxypolyethylene glycol (mPEG) modified Dp-extract. Patients were monitored by annual challenges with histamine in bronchi, and Dp allergen in bronchi, nose and conjunctiva. mPEG-modified extract was not inferior to unmodified Dp-extract; both were to some extent able to improve tolerance to Dp and histamine in bronchi and to Dp in nose and eyes. During the 1st year, the bronchial sensitivity to Dp decreased significantly in the HS groups but not in the Ctls. During the 2nd year, improvement was more pronounced in the Ctl group. The relative increase in Dp or histamine tolerance did not differ significantly between groups after either 1 or 2 years; the only exception was conjunctival sensitivity, which in the Ctl group was unchanged, and a 10-fold increase in tolerance in the HS groups. No direct benefit was seen on late-phase bronchial reactions. In patients with improved pulmonary symptoms a tendency was seen towards reduced sensitivity to histamine and Dp. Variation within groups was extensive.

Animals↗

Immunotherapy with dog and cat allergen preparations in dog-sensitive and cat-sensitive asthmatics.

Standardized dog and cat allergen preparations with defined allergen composition were used for immunotherapy (IT) in dog-sensitive and/or cat-sensitive adult patients. Seventeen patients completed 1 year of IT. Eleven patients were treated with dog allergen, five with cat allergen, and one with both dog and cat allergen. The treatment was well tolerated, with increased subjective tolerance. After 3 months of IT there was a significant decrease in conjunctival (p less than .05) and skin sensitivity (p less than .05). Specific IgE decreased significantly within 1 year as assayed by RAST and IgE-crossed radioimmunoelectrophoresis. Specific IgG increased in all patients. The results indicate that IT with potent and standardized dog and cat allergens influence the sensitivity to these allergens.

Allergens↗

Comparison between modified skin prick test with standardized allergen extracts and Phazet.

Skin prick tests (SPTs) represent one of the most common techniques of skin testing and are of great value, especially when standardized extracts are used. Phazet is a puncture test involving needles coated with standardized allergens. Phazet and SPTs have been compared in 130 subjects tested with six standardized allergen extracts: orchard-grass, olive, and mugwort pollens, cat dander, Dermatophagoides pteronyssinus, and Alternaria. Patients have been carefully selected on the basis of a suggestive clinical history, SPTs, and RAST. For all allergenic species, at least 20 nonsensitive individuals have been tested. The sensitivity (true positive in percent of patients with disease) of Phazet was 99.4%, and its specificity (true negative in percent of patients without disease) was 99.2%. It is concluded that Phazet and SPTs with standardized extracts are equally effective in the diagnosis of immediate-type allergy and that standardized extracts have improved the diagnosis of allergy, especially for previously poorly characterized extracts, such as Alternaria.

Adolescent↗

Breed-specific dog-dandruff allergens.

Fifty-one patients with clinical history of dog allergy were skin prick tested with eight individual standardized dog breed-allergen preparations, one mixed breed-allergen preparation (Poodle/Alsatian), dog-serum albumin, and histamine hydrochloride, 1 mg/ml. All extracts were characterized by crossed immunoelectrophoresis and crossed radioimmunoelectrophoresis with a pool of sera from patients clinically sensitive to dog. The dog-breed extracts contained common antigens/allergens, as well as components represented only in one or two dog-breed extracts. The concentration corresponding 1000 BU/ml varied from 16 to 100 micrograms of protein per milliliter. The sensitivity of skin prick test was 67% to 88% for the various dog breed-allergen preparations, but only 18% for dog-serum albumin. Significant difference between the skin test response to different dog breed-allergen preparations indicating dog breed-specific allergens was obtained in 15% of the patients. There was no significant correlation between skin prick test results and symptoms related to a specific dog breed.

Adolescent↗

Effective hyposensitization in allergic rhinitis using a potent partially purified extract of house dust mite.

Thirty-eight adults with allergic rhinitis have been treated with a new partially purified extract of house dust mite (Dermatophagoides pteronyssinus) in a double-blind placebo-controlled trial. Patients were randomized to active (Pharmalgen, D. pteronyssinus) and placebo (histamine) treatment by sensitivity to D. pteronyssinus on nasal challenge. In the actively treated group nasal symptoms, assessed by visual analogue score, improved (P less than 0.01), sensitivity on nasal challenge with allergen was reduced (P less than 0.05) and weal size on skin-prick test with allergen was reduced (P less than 0.01), compared with the placebo group. These results occurred after 3 months of treatment. Reduction in target organ sensitivity occurred, while the serum level of D. pteronyssinus IgE rose in the active group from 14.2 to 22.5 PRU/ml (geometric mean) but did not change significantly in the placebo group. As anticipated, because of the treatment schedule used, a number of generalized allergic reactions were induced by injections, but all responded promptly and easily to treatment. These results suggest this is an effective form of therapy, which now offers us the opportunity to study the immunological mechanisms of hyposensitization and to devise a modified schedule causing fewer reactions.

Adolescent↗

Allergy screening including a comparison of prick test results with allergen-coated lancets (Phazet) and liquid extracts.

During an allergy screening of families with a history of allergy in one or more subjects, skin prick tests (SPT) were performed in duplicate in 314 adults. The tests were performed with a new type of lancet with a 0.9 mm long point, loaded either with allergen (Phazet) or used together with standardized extracts (10,000 and 100,000 BU/ml). Wheals obtained with both methods were compared, and related to total IgE concentrations and history. A wheal area of 3 and 7 mm2 was used as cut-off limit. Results with Phazet were close to those with Pharmalgen 100,000 BU/ml. With both methods precision was good for allergens, but less for Phazet histamine than for the corresponding wet test. SPT results obtained with Phazet and 100,000 BU/ml correlated better with history than the results with 10,000 BU/ml. Using a wheal size of 7 mm2 as cut-off limit the efficiency for five tested allergens was 91%. "False positive" tests, possibly indicating an unobserved or latent type of allergy, were found more often with higher serum IgE concentrations. The safety of SPT was confirmed and Phazet was well accepted by nurses and tested subjects.

Adult↗

Modification of house dust mite allergens by monomethoxypolyethylene glycol. Allergenicity measured by in vitro and in vivo methods.

In animal models, allergen modification by coupling to monomethoxypolyethylene glycol (mPEG) molecules can reduce allergenicity of the extract and makes the allergen capable of suppressing boosted IgE response. To investigate in a human system the degree of attenuation implied by a mPEG modification of a house dust mite (Dermatophagoides pteronyssinus) extract, 55 adults with asthma caused by house dust mites were tested by skin prick test (SPT) and histamine release assay (HR). RAST inhibition was performed on sera from 6 additional patients. Modified extract containing 0.42 mmol mPEG/g protein was used for the analyses. In order to get the same response of the two extracts when assessed by HR and SPT, a median increase in concentration of 10-fold of the mPEG-modified extract compared to the unmodified extract was needed. Interindividual variation was limited. Sixty-four to 72% needed a dose increase within +/- half a decade from this value. In 42-49% of the patients, results from SPT and HR deviated less than half a decade. The relative potency of the modified extract as measured by RAST inhibition was reduced to 17-78% (mean 39%). Reduced allergenicity would by itself mean less side effects in immunotherapy. When planning such therapy it is important to know that mPEG modification reduces the allergenicity to a similar extent in a majority of patients.

Allergens↗

A double-blind study comparing monomethoxy polyethylene glycol-modified honeybee venom and unmodified honeybee venom for immunotherapy. I. Clinical results.

Thirty-five patients were allocated at random to immunotherapy (IT) in a double-blind way with either monomethoxy polyethylene glycol (mPEG)-modified honeybee venom (HBV) or HBV. The two groups were well matched regarding age, sex, skin sensitivity, HBV-specific serum IgE and IgG antibodies, and history of reactions after a field sting; mPEG-HBV-treated patients received doses that increased more steeply than doses of the HBV-treated patients. The maintenance dose of the former group (200 micrograms) was greater than that of the latter group (100 micrograms). During IT, both groups had the same frequency of local swellings after injections. Four patients receiving mPEG-HBV developed one mild systemic reaction (SR) during dose increase, whereas 10 patients receiving HBV demonstrated one or more of these reactions, compelling two patients to stop therapy. Following challenge with a honeybee sting after about 14 weeks of IT, six patients with SR were observed, four in the mPEG-HBV-treated group and two in the HBV-treated group. In the HBV-treated group, three patients were not challenged, one because of an insufficient IgG increase and two other patients because they dropped out of IT before reaching maintenance dose because of repeated SRs. Since the mPEG-HBV is extremely well tolerated during IT and the success rate is not significantly lower than with unmodified HBV, we suggest it as an attractive alternative to HBV for the treatment of HBV hypersensitivity. Increase of the maintenance dose may result in an even better clinical efficacy.

Adolescent↗

Oral immunotherapy in birch pollen hay fever.

Previous controlled trials with oral administration of allergen have not demonstrated any treatment effect in patients with allergic rhinoconjunctivitis or asthma. In the present double-blind, placebo-controlled trial, we have tested the effect of oral immunotherapy in adult patients with birch pollinosis. Thirty-nine patients completed this 18-month study comprising two birch pollen seasons. The patients received enterosoluble capsules daily, and the actively treated patients reached a cumulated dose of 280 times 10(6) biologic units of birch pollen extract, which is about 200 times higher than the dose used in conventional subcutaneous immunotherapy. We found a significant decrease in eye symptom scores and conjunctival sensitivity to birch pollen, as determined by conjunctival provocation test, as well as a numerical but nonsignificant decrease in nasal symptom scores, nasal sensitivity as determined by nasal provocation test, and antiallergic medication. The treatment was safe, and only a few slight side effects were observed. We thus conclude that our study demonstrates a clinical effect of oral immunotherapy in birch pollinosis.

Administration, Oral↗

Biological equilibration of allergen preparations: methodological aspects and reproducibility.

A method for biological equilibration (BE) of allergen reference preparations using the skin-prick test (SPT) method and histamine HCl 10 mg/ml as reference substance (reference method), was evaluated. The precision was low for weals less than 10 mm2. The slope (log weal area/log concentration) of allergen and histamine did not vary significantly between investigators and allergens. The median slopes were 0.39 (n = 384) and 0.34 (n = 397), for allergen and histamine, respectively (P less than 0.01). The concentration of allergen eliciting a weal of the same size as that of histamine HCl 1 mg/ml (Chl) in the median sensitive patient, 1000 Biological Units/ml (BU/ml), did not vary significantly between clinics/geographical regions (grasses, mites and moulds). As BE is repeatable between regions, BUs estimated by this method are generally valid. A high correlation (r = 0.91, P less than 0.001) was found between the median Chl as estimated with histamine 1 and 10 mg/ml as reference substance, respectively. Thus, this reference method for BE is valid. The precision of the SPT method with histamine HCl 1 mg/ml is not as good as with 10 mg/ml, which is therefore recommended as the reference concentration.

Adolescent↗

Immunotherapy to deciduous tree pollens: specific IgE and IgG antibody patterns.

Thirty-nine children with birch pollinosis were given immunotherapy (IT) for 3 years with a purified, characterized and biologically standardized pollen preparation made from either birch or a mixture of birch, alder and hazel. Levels of IgE antibodies against birch, alder and oak increased early during IT (P less than 0.01) and then decreased below the initial level (P less than 0.01). Birch-specific IgG antibodies also increased (P less than 0.01) but not as rapidly as birch-specific IgE antibodies and the levels remained increased throughout IT. There were only weak correlations between immunochemical findings before IT or during early IT on one hand and the improvement during IT on the other hand. The ratio birch-specific IgG:IgE after 1.5 and 2.5 years of IT correlated with symptom scores the following season (P less than 0.01). In 60% of the children below 13 years of age, new IgE specificities developed during IT as demonstrated with crossed radioimmunoelectrophoresis. No such new IgE specificities were found in older children. These 'new sensitivities' did not appear to have any clinical implication.

Adolescent↗