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Biomedical subjects

M van Hage-Hamsten

Publications and source records attributed to M van Hage-Hamsten.

At least 73 records · Page 4Linked to original sources
PubMed1997

Increased allergen-specific Th2 responses in vitro in atopic subjects receiving subclinical allergen challenge.

The study aimed to determine whether inhalation of subclinical allergen doses-leads to a shift in the balance between T helper (Th) 1 and Th2 cells in asthmatic patients. Elevated IgE requires allergen-specific T cells producing cytokines such as interleukin (IL)-4 or IL-13. Interferon-gamma (IFN-gamma) produced by Th1 cells counteracts the effects of IL-4. In nature, allergic persons are often exposed to low levels of allergen, leading to hyperreactivity, but not to acute allergic reactions. In this study, nine allergic persons inhaled low doses of allergen or placebo in a double-blind manner over seven consecutive weekdays. During the study, the bronchial responsiveness to histamine challenge increased, but no subject exhibited asthmatic symptoms. Blood was drawn on days 0, 1, 4, and 9, and the number of IL-4- and IFN-gamma-producing cells was measured by enzyme-linked immunospot (ELISPOT) assay after in vitro stimulation with a low-dose phytohemagglutinin (PHA) mixed with the relevant allergen or with PHA alone. In three of the four subjects receiving allergen, the IL-4/IFN-gamma ratio increased during the time of the study. No increase was seen in the placebo group. No increase was seen in serum IgE levels in any of the groups. We conclude that a shift in the balance between Th1 and Th2 cells can be detected in subjects exposed to subclinical allergen doses.

Allergens↗
PubMed1997

Allergenic crossreactivity between Lepidoglyphus destructor and Blomia tropicalis.

BACKGROUND: In general, the non-pyroglyphid mites Lepidoglyphus destructor and Blomia tropicalis show a different geographical distribution. Allergic sensitization to both species have been demonstrated in several investigations. However, whether this reflects cross-reactivity or dual sensitization is so far not known. OBJECTIVE: The aim of the study was to investigate the allergenicity and allergenic crossreactivity of L. destructor and B. tropicalis using sera from Sweden and Brazil. METHODS: Allergens in extracts of L. destructor and B. tropicalis were identified with SDS-PAGE and immunoblotting and the crossreactivity was studied by an immunoblot inhibition method. In addition to mite extracts, a recombinant major allergen of L. destructor, Lep d 2, was used. RESULTS: The extract prepared from L. destructor contained 21 IgE-binding components when using the Swedish or the Brazilian sera. A 15 kDa allergen was recognized by 85% of the Swedish sera and 78% of the Brazilian. The B. tropicalis extract exposed 23 IgE-binding components when the Brazilian sera were used and 19 when the Swedish sera were used. A total of 83% of the Brazilian sera and 80% of the Swedish sera identified a 14.5 kDa allergen. The IgE response of the Swedish serum pool to 10 B. tropicalis allergens was inhibited by L. destructor extract. Likewise, the response of the Brazilian serum pool to four different L. destructor allergens was inhibited by B. tropicalis extract. The recombinant Lep d 2 allergen inhibited 33% of the IgE binding of the Swedish serum pool to the 14.5 kDa allergen in the B. tropicalis extract. CONCLUSION: Crossreactivity with several proteins from L. destructor and B. tropicalis was demonstrated. The results suggest that a B. tropicalis 14.5 kDa allergen is antigenically crossreactive with recombinant L. destructor allergen Lep d 2.

Allergens↗
PubMed1996

Distribution of plasma cell markers and intracellular IgE in cell line U266.

The IgE-producing plasma cell line U266 was used to study intracellular IgE and the distribution of the plasma cell markers CD38 and PCA-1. We found two separate clusters of U266 based on the differences in their light scatter properties in the flow cytometer. One cluster displayed high scatter signals (high SS), whereas the other showed low scatter signals (low SS). Most (75%) of the cells in the low SS cluster were positive for intracellular IgE. In contrast, high SS cells had a higher expression of surface IgE and a considerably lower proportion of these cells expressed intracellular IgE. Different patterns of expression of the plasma cell antigens CD38 and PCA-1 were observed. While the low SS cluster displayed a high (76%) expression of PCA-1 and a low (5%) CD38 expression, the high SS cluster expressed 21 and 42%, respectively. About 2/3 of the cells in the low SS cluster appeared to be in the G1 phase of the cell cycle while 1/3 were in the S/G2 phase. In the high SS cluster the opposite distribution (2/3 in S/G2) was observed. Taken together our results indicate an association between cell cycle stages, expression of intracellular IgE and plasma cell markers.

ADP-ribosyl Cyclase↗
PubMed1996

Anti-IgE-induced accumulation of leukocytes, mediators, and albumin in skin chamber fluid from healthy and atopic subjects.

The aim of this study was to examine potential differences between healthy and atopic subjects with regard to IgE-mediated cutaneous inflammation. For this purpose, we analyzed histamine, tryptase, leukotriene B4, albumin, eosinophils, and total leukocytes in skin chamber fluid after challenge with anti-human IgE. We also measured gross skin reactivity (wheal, flare, and late-phase reactions), circulating IgE, and eosinophils, as well as the state of eosinophil activation. It was found that despite having more circulating IgE, the skin responsiveness of the atopic subjects did not differ significantly from that of the nonatopic subjects with respect to mediator release, albumin extravasation, or total recruitment of leukocytes. Moreover, the sizes of anti-IgE-induced wheal, flare, and late-phase reactions were very similar in the two groups. On the other hand, significant recruitment of eosinophils during the IgE-mediated reaction was more or less restricted to the atopic group. Yet the recruited eosinophils, of which the majority was in an early state of activation before degranulation, did not seem to contribute significantly to the IgE-mediated delayed skin edema. Furthermore, the eosinophil count in anti-IgE chambers of the atopic subjects did not correlate with any of the other parameters monitored. Thus because the anti-IgE-induced recruitment of eosinophils appeared to be unrelated to factors such as the number of peripheral blood eosinophils, the degree of mast cell activation, the intensity of inflammatory skin changes, and the level of circulating IgE, it is apparent that the mechanisms for and pathophysiologic role of IgE-mediated dermal eosinophil accumulation in atopic subjects require further investigation.

Antibodies, Anti-Idiotypic↗
PubMed1996

Allergen-induced inflammation in the nose: a comparison of acute and repeated low-dose allergen exposure.

To investigate allergic rhinitis induced by two experimental provocation models, we compared local inflammation with markers of eosinophil activity in peripheral blood. Patients with strictly seasonal allergic rhinitis were selected and investigated outside the pollen season. An acute challenge with increasing doses of allergen every 15 min until symptoms occurred was performed in nine patients. Nasal lavage and blood samples were taken before and 4 and 24 h after challenge. After a 6-week washout period, 10 patients were submitted to 7 days of repeated low allergen exposures. One small dose (approximately equal to 1/100 of the acute dose) was given each day. Blood and lavage samples were taken prior to and after the period. As control four patients were challenged with diluent only. The acute challenge resulted in sneezing and nasal discharge and blockage and was accompanied by a rise in histamine and eosinophil cationic protein (ECP) in lavage fluid after 4 h and continuing after 24 h, when there also was a rise in the number of eosinophils and ECP in peripheral blood. The repeated low-dose exposures caused very few symptoms but produced increased ECP in the lavage fluid and a trend toward increased histamine concentration. There were no changes in ECP, intracellular EG2 binding, or number of eosinophils in the blood. No changes were seen in the control group. Our findings show that changes in eosinophil mediator release in nasal lavage can be seen after very low, but repeated, allergen exposures despite no, or minimal, clinical symptoms.

Adult↗
PubMed1996

ELISA method for detection of mite allergens in barn dust: comparison with mite counts.

ELISA (enzyme-linked immunosorbent assay) inhibition with a monoclonal antibody (mAb) (42B6) to Lepidoglyphus destructor was used to detect and quantify the storage-mite allergens in 30 dust samples collected from barns. Regarding the mite fauna, microscopic inspection of the barn dust and mite counts showed that L. destructor infested all 30 barns investigated (range 430-195 400 mites/g dust). In 29/30 barns, L. destructor constituted more than 70% of the Astigmata species. Acarus siro was found in 26 samples, the highest value being 16155 mites/g. No Dermatophagoides species were found. As to mites of the suborder of Prostigmata, species belonging to seven different families were detected. Besides the predominant L. destructor, allergens derived from other storage mites such as Glycyphagus domesticus, A. siro, and Tyrophagus putrescentiae have previously been assessed by this ELISA method. The correlation between number of mites and concentrations of mite antigen as measured by ELISA was assessed by linear regression (r2 = 0.83). Thus, inhibition of mAb 42B6 in ELISA would seem to offer a simple and reliable method to detect levels of dust-mite species belonging to the Acaridae and Glycyphagidae families.

Agricultural Workers' Diseases↗
PubMed1996

Effects of salmeterol and terbutaline on IgE-mediated dermal reactions and inflammatory events in skin chambers in atopic patients.

The objective of the present study was to investigate the potential of the long-acting beta 2-agonist salmeterol as an inhibitor of various components of IgE-mediated inflammatory in man. For this purpose, we measured gross skin reactivity (diameters of wheal and flare reaction [WFR] and late cutaneous reaction [LCR] as well as inflammatory cells, mediators, and protein in cutaneous suction blister chambers in eight subjects with allergic rhinitis. Blisters were induced, two on each forearm, by gentle suction and heating, and were unroofed 12 h later, after which plastic chambers were placed over the denuded area. The chambers were challenged for 2 h with antihuman IgE (titer 1:10) in the presence and absence of salmeterol or terbutaline. Normal goat IgG served as negative control. Chamber fluids were removed hourly for the first 4 h, and this followed by a 4-h incubation before final collection. Salmeterol (10(-6)M) and terbutaline (10(-5)M) injected intradermally 30 min before, aw well as together with anti-IgE (titer 1:100), inhibited the WFRs by up to 30%. The effect of salmeterol on the ensuing LCR (75% inhibition at 24 h) tended to be more pronounced than the corresponding inhibition by terbutaline. Both salmeterol and terbutaline very effectively inhibited the anti-IgE-induced extravasation of alpha 2-macroglobulin into skin chambers, with a significantly more sustained effect by salmeterol. Interestingly, only terbutaline reduced the histamine release evoked by anti-IgE. With the present experimental design, where both drugs were washed out from the chambers after 2 h, neither drug inhibited recruitment of leukocytes (including eosinophils). Taken together, salmeterol had a more sustained inhibitory effect than terbutaline on indices of IgE-mediated edema formation (late induration and plasma protein extravasation). On the other hand, under the present experimental conditions, salmeterol failed to reduce the histamine release (in contrast to terbutaline), and neither salmeterol nor terbutaline affected the recruitment of leukocytes.

Administration, Cutaneous↗
PubMed1996

Eosinophil cationic protein in tears in allergic conjunctivitis.

AIMS/BACKGROUND--Eosinophil cationic protein (ECP) is a quantifiable product secreted by activated eosinophils. The aim of this study was to assess the degree of eosinophil activity in different clinical stages of various forms of allergic conjunctivitis. METHODS--Tears were collected in glass capillary tubes from 14 subjects with seasonal allergic conjunctivitis (SAC), 23 subjects with vernal keratoconjunctivitis (VKC), 16 subjects with atopic keratoconjunctivitis (AKC), 10 subjects with giant papillary conjunctivitis (GPC), and 16 healthy control subjects. The samples were analysed in duplicate with a radio-immunoassay for ECP. RESULTS--Statistically significant differences were evident between healthy controls and allergic subjects (p < 0.001). Subjects with AKC and VKC had significantly higher tear ECP values than subjects with GPC and SAC. In addition, there was a significant correlation between ECP values and disease severity in all disorders. CONCLUSION--The data suggest a particular pathogenic role of the eosinophil in VKC and AKC, and a less pronounced but still important eosinophil involvement in the disease processes of GPC and SAC.

Adolescent↗
PubMed1996

Sustained eosinophil cationic protein release into tears after a single high-dose conjunctival allergen challenge.

BACKGROUND: The appearance of eosinophils is a hallmark sign of the allergic late-phase response (LPR). Eosinophil cationic protein (ECP), a readily measurable product released from activated eosinophils, has so far not been evaluated in the ocular LPR. OBJECTIVE: Two sets of trials were performed in order to investigate changes of local and systemic eosinophil activity and their possible link with symptoms and hyperreactivity in the allergic LPR in the eye. METHODS: In the first experiment, ECP was analysed in tears and serum and the clinical reaction was evaluated during a 72-h time-course after a single, high-dose allergen challenge out of season in one eye of 15 pollen-sensitized volunteers. In a second experiment, the hypothesis of an increased clinical response to an allergen challenge in an eye that had been provoked with allergen 48 h previously was tested in nine sensitized individuals. RESULTS: In the first experiment, symptoms at 10 min and 2, 4, 6, 8 and 24 h significantly exceeded base line scores of the challenged eyes. Tear ECP was significantly elevated in challenged eyes compared to contralateral eyes at 6, 8 and 24 h. In addition, symptoms and ECP release correlated significantly at the 24-h evaluation. Serum ECP remained unchanged throughout the study period. In the second experiment, conjunctival hyperreactivity 48 h after an allergen challenge was not confirmed. CONCLUSION: ECP secretion occurs in the experimental ocular LPR and is in part associated with the magnitude of the clinical reaction, which suggests a truly pathogenic role of the activated eosinophil in pollen-induced allergic conjunctivitis.

Administration, Topical↗
PubMed1995

Immunoglobulin E, mast cell-specific tryptase and the complement system in sudden death from coronary artery thrombosis.

We tested the hypothesis of anaphylaxis as a pathogenic factor in acute myocardial infarction. Mast cells were counted in the myocardium, coronary arteries and airways. Total serum IgE, mast cell tryptase, complements C3, C4, and factor B, were measured in 29 cases of sudden death from coronary artery thrombosis and in 27 controls. We found increased numbers of mast cells in the coronary arteries following coronary death: 46 +/- 21 (SD) compared with 22 +/- 10 (SD) in the control group (P < 0.002). In the myocardium and airways there were no differences between the groups. The concentrations of tryptase and IgE in serum did not differ between the groups although 20% of the coronary deaths had elevated values (> 200 kU/l) compared with 8% in the control group. Of the complement factors, C3 was higher in the coronary deaths (P < 0.05) than in the controls. The results give no evidence of anaphylactic reaction in the pathogenesis of acute myocardial infarction.

Anaphylaxis↗
PubMed1995

cDNA analysis of the mite allergen Lep d 1 identifies two different isoallergens and variants.

For the first time the complete cDNA encoding two isoallergens of the non-pyroglyphid dust mite Lepidoglyphus destructor, Lep d 1, allergen has been sequenced. In addition, one of the isoallergens was found to have two variants. Oligonucleotides were designed from known amino acid sequences. The cDNA sequences were obtained by hybridizing these primers to mRNA and enhancement by the RT-PCR technique. To obtain the different complete encoding cDNA sequences and eliminate heteroduplex artifacts, we performed PCR + 1 reactions. Comparison of the amino acid sequence of the allergen shows leader sequences of 16 amino acids for both isoforms.

Amino Acid Sequence↗
PubMed1995

Effects of loratadine on anti-IgE-induced inflammation, histamine release, and leukocyte recruitment in skin of atopics.

The aim of this study was to assess the ability of the H1-receptor antagonist loratadine to modify anti-IgE-induced cutaneous wheal-and-flare and late-phase reactions (WFR and LPR), as well as histamine release and leukocyte accumulation in skin chambers. For this purpose, 10 atopics with allergic rhinitis were entered into a double-blind crossover study in which they received either placebo or loratadine (20 mg/day orally) for 8 days separated by a 7-day washout period. Blisters were induced on both forearms on day 7 of each treatment period, and were unroofed on day 8 and covered with plastic skin chambers. Chamber fluids were collected during 7 h after 1-h incubation with anti-IgE or control IgG. Intradermal challenge with histamine and anti-IgE was performed at the same occasion. As compared to placebo treatment, loratadine inhibited the immediate WFRs to anti-IgE by 35% (wheal) and 65% (flare), respectively (P < 0.01), and corresponding reactions to histamine challenge by 50% and 70% (P < 0.001), respectively. Moreover, the initial phase (0-2 h) of the LPR induced by anti-IgE was attenuated by up to approximately 60% (P < 0.001) during loratadine treatment. Thereafter, no inhibition of the LPR was observed. The magnitude and time course of histamine release into skin chambers was virtually the same after loratadine and placebo treatment, with a peak during 0-1 h and a progressive decline during the following 2 h. Accumulation of alpha 2-macroglobulin, reflecting extravasation of large plasma proteins, also peaked during the first hour and was unaffected by loratadine during the 8-h observation period.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

IgG1 and IgG4 antibody responses to the dust mite Lepidoglyphus destructor in a naturally exposed farming population.

The natural humoral immune response to the dust mite Lepidoglyphus destructor was assessed by comparing the IgG1 and IgG4 responses elicited in allergic (n = 44) and healthy (n = 16) individuals in a farming population chronically exposed to this allergen. With the aid of an immunoblotting technique and ELISA, the sera were analyzed for anti-L. destructor antibodies. While the majority of sera from the allergy group displayed several bands for both IgG1 and IgG4, the nonatopic healthy group was negative as analyzed in immunoblotting. When they were analyzed in ELISA, there was a significantly higher response in the allergy group than in the healthy group for IgG4, but not for IgG1. Taken together, these results imply that the immune system of individuals spared from allergic reactions to L. destructor not only lacks IgE antibodies but also seems largely to "ignore" these allergens/antigens despite exposure.

Agriculture↗