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Biomedical subjects

C Schou

Publications and source records attributed to C Schou.

At least 37 records · Page 2Linked to original sources
PubMed1997

Crossreactivity and T-cell epitope specificity of Bet v 1-specific T cells suggest the involvement of multiple isoallergens in sensitization to birch pollen.

BACKGROUND: Allergen-specific T lymphocytes play an important role in the pathophysiology of atopic disease. Detailed studies of their epitope-specificity and crossreactivity are required for the development of novel approaches for specific immunotherapy. OBJECTIVES: The aim of the study was to characterize the fine specificity of Bet v 1-specific T cells from allergic donors. METHODS: Polyclonal T-cell lines (TCL) and T-cell clones (TCC), specific for Bet v 1, the major birch (Betula verrucosa) pollen allergen, were isolated from the peripheral blood of three birch-allergic patients. Their epitope-specificity was studied using overlapping synthetic peptides, and crossreactivity with other tree pollen allergens of the Fagales order was evaluated. In addition, the Bet v 1-specific TCC were studied for their phenotype and cytokine production. RESULTS: All isolated Bet v 1-specific TCC (19/21 CD4+, 2/21 CD8+) reacted with affinity purified Bet v 1, but showed different reactivities with recombinant Bet v 1 (rBet v 1), and with group 1 allergens from other Fagales species. Epitope mapping of rBet v 1-reactive TCC with synthetic peptides of Bet v 1 showed the presence of four T-cell epitopes. Polyclonal T-cell lines reacted with 13 different peptides, and displayed even broader crossreactivity with group 1 pollen allergens from other Fagales members. CONCLUSION: This study demonstrates that apart from T-cell epitopes of rBet v 1, many other crossreactive or Bet v 1 isoallergen-specific epitopes exist. This indicates that isoallergenic variation plays an important role in the induction of Bet v 1-specific and crossreactive T-cell responsiveness to allergens.

Allergens↗
PubMed1996

Linkage of asthma and total serum IgE concentration to markers on chromosome 12q: evidence from Afro-Caribbean and Caucasian populations.

To identify genes potentially relevant in atopic asthma, we analyzed markers in chromosome 12q15-q24.1 for linkage to asthma and total serum IgE concentration. Sib-pair analyses of 10 markers in 345 full- and 219 half-sib pairs from 29 multiplex Afro-Caribbean families provided evidence for linkage to this region for both asthma and total serum IgE. Certain alleles at these loci showed significant evidence of transmission disequilibrium with both asthma and high IgE. Using 6 of these markers and 11 additional markers, evidence for linkage of total IgE to 12q was also found in 12 Caucasian Amish kindreds (24 nuclear families) by both sib-pair and transmission disequilibrium analyses. These findings suggest that the 12q15-q24.1 region may contain a gene(s) controlling asthma and the associated "high total IgE" trait.

Adolescent↗
PubMed1996

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↗
PubMed1996

Diagnostic significance of in vitro T-cell proliferative responses to house-dust mite Der p 1 in children with dust-mite allergy.

The study aimed to investigate the possible diagnostic significance of T-cell proliferative responses to purified Der p 1 antigen in allergic children with and without allergic sensitization to house-dust-mite (HDM) allergens. T-cell reactivity to purified Der p 1 antigen was analyzed in 24 children with allergic sensitization to HDM demonstrated by RAST and/or positive skin prick tests. Twelve healthy young adults and 11 children with allergic sensitizations other than HDM served as controls. Of 25 HDM-allergic patients, 16 displayed strong T-cell reactivity to Der p 1 (stimulation indices > 3): nine patients showed no T-cell proliferation despite the presence of specific IgE, and five showed no responses despite positive skin prick test. In two patients, a weak T-cell response to Der p 1 could be demonstrated in the absence of specific IgE and negative skin test result. The two affected subjects did not show evidence of mite allergy. No T-cell responses were observed in adult controls (stimulation indices < 3). We conclude that the assessment of T-cell reactivity to Der p 1 is of little value for the diagnosis of HDM allergy. The importance of T-cell proliferative responses for the study of the pathogenesis of HDM allergy remains unchallenged.

Adolescent↗
PubMed1996

Childhood asthma and exposure to indoor allergens: low mite levels are associated with sensitivity.

The prevalence and level of sensitivity to indoor allergens were studied in relation to current exposure at home in 124 children with perennial asthma living in three climatic zones of Sweden. The house dust mite (HDM) allergen levels were higher in the South than in the North (p < 0.001), while cat and dog allergen levels tended to be higher in the North than the South (n.s.). Thirty-four percent of the children were sensitive to the HDM Dermatophagoides pteronyssinus, as determined by IgE antibodies in vitro, 27% were sensitive to D. farinae, 57% to cat and 55% to dog. Sensitivity to HDM was significantly more prevalent in Southern, than in Central and Northern Sweden (p = 0.001) where the children were more often sensitive to pets (cat p = 0.005, dog p = 0.002). A significant association between the concentration of Der p I and Der fI in the house dust and both the prevalence of sensitivity to HDM and the IgE antibody levels against mites was found even at concentrations well below the commonly suggested risk level for sensitisation of 2 micrograms/g dust. No relationship was found between pet allergen concentration in the home dust and sensitivity to pets, possibly because of exposure outside home, e.g. in schools and meeting places for leisure activities. Similarly, there was no consistent association between the level of mite or pet allergen exposure at home and asthma severity as judged by symptom and medication score. The study indicates that there is no threshold value for sensitisation to mite allergens in asthmatic children, and therefore, dust allergen levels at home should be kept as low as possible in homes of children at risk for asthma.

Adolescent↗
PubMed1995

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↗
PubMed1995

Identification of important allergenic proteins in extracts of the granary weevil (Sitophilus granarius).

This paper describes the identification of important allergens from the granary weevil (Sitophilus granarius) (Sg). Sera from Danish bakers whose skin prick tests were positive to extracts of Sg were screened for IgE against Sg extracts. We found that 54% (n = 66) had elevated levels of IgE (RAST classes 1-3, by luminescent immunoassay) against whole-body extracts of Sg. The specificity of patient IgE was investigated in an inhibition-dot immunoblotting assay. IgE binding was inhibited in all sera but two, thus indicating that the patients' IgE was indeed specific for the Sg extract. In crossed immunoelectrophoresis, 23 different proteins were identified. All RAST-positive sera were investigated in crossed radioimmuno-electrophoresis. At least 11 proteins in the Sg extract were capable of binding IgE. All individual sera reacted with at least four different proteins. The two most prominent allergens bound IgE from 88% and 100%, respectively, of the patients. These two are considered to be the most important allergens from Sg, and will be useful as markers in environmental immunochemical assays to detect allergens in samples from bakeries, grain stores, etc.

Adolescent↗
PubMed1994

Genetic linkage of T-cell receptor alpha/delta complex to specific IgE responses.

IgE responses to inhaled proteins underlie the clinical syndrome of allergic (atopic) asthma and rhinitis. We have investigated genetic linkage between specific IgE reactions to highly purified major allergens and the T-cell receptor (TCR) alpha and beta gene complexes on chromosome 14 and 7, respectively. Antigens tested included highly purified proteins from the housedust mite Dermatophagoides pteronyssinus, the domestic cat and dog, grass pollen, and the mould Alternaria alternata. Affected sibling-pair methods were used in two independent sets of families, one in the UK and one in Australia. No linkage of IgE serotypes to TCR-beta was detected, but significant linkage to TCR-alpha was seen in both family groups. For several of the IgE phenotypes investigated (positive responses to whole allergen sources or purified antigens or serum IgE above the 70th percentile in the population) the affected sibling-pairs showed significant sharing of TCR-alpha microsatellite alleles from both parents. The results show that a gene (or genes) in the TCR-alpha region modifies specific IgE responses.

Alleles↗
PubMed1994

Linkage analysis of IL4 and other chromosome 5q31.1 markers and total serum immunoglobulin E concentrations.

Sib-pair analysis of 170 individuals from 11 Amish families revealed evidence for linkage of five markers in chromosome 5q31.1 with a gene controlling total serum immunoglobulin E (IgE) concentration. No linkage was found between these markers and specific IgE antibody concentrations. Analysis of total IgE within a subset of 128 IgE antibody-negative sib pairs confirmed evidence for linkage to 5q31.1, especially to the interleukin-4 gene (IL4). A combination of segregation and maximum likelihood analyses provided further evidence for this linkage. These analyses suggest that IL4 or a nearby gene in 5q31.1 regulates IgE production in a nonantigen-specific (noncognate) fashion.

Adolescent↗
PubMed1994

Association between HLA-DRB3*0101 and immunoglobulin-E responsiveness to Bet v I.

The relationship between HLA-DRB3 antigens and specific IgE responsiveness to highly purified major allergen from white birch (Betula verrucosa), Bet v I, was studied in 43 patients, who were skin-prick test positive to birch pollen extract. Specific IgE to Bet v I was measured using an assay based on the principle of the Magic Lite method. HLA-DR and -DQ typings were performed by standard restriction fragment-length polymorphism techniques and HLA-DRB3 typing by the use of polymerase chain reaction and sequence-specific oligonucleotide. Of the 43 patients, 41 (95%) exhibited Bet v I-specific IgE. The data showed a significant association between HLA-DRB3*0101 and specific IgE to Bet v I (pc = 0.02). Furthermore, it was shown that this association was linked to the overall IgE responsiveness and not to a limited area of IgE sensitivity. The present study confirms and further identifies the association of DRB3*0101/0301 earlier described in an Austrian population to be present also in a Danish study group. This underlines the importance of this particular allele in the allergic immune response to birch pollen and emphasizes the importance of investigating the molecular basis of human allergic immune responsiveness.

Allergens↗
PubMed1994

HLA-DR and HLA-DP genotypes and immunoglobulin E responses to common major allergens.

In order to test for human histocompatibility leucocyte antigens (HLA) class II restriction of IgE responses, 431 subjects from 83 families were genotyped at the HLA-DR and HLA-DP loci and serotyped for IgE responses to six major allergens from common aero-allergen sources. A possible excess of HLA-DR1 was found in subjects who were responsive to Fel d I compared with those who were not (Odds Ratio (OR) = 2, P = 0.002), and a possible excess of HLA-DR4 was found in subjects responsive to Alt a I (OR = 1.9, P = 0.006). Increased sharing of HLA-DR/DP haplotypes was seen in sibling pairs responding to both allergens. Der p I, Der p II, Phl p V and Can f I were not associated with any definite excess of HLA-DR alleles. No significant correlations were seen with HLA-DP genotype and reactivity to any of the allergens. The results suggest class II HLA restriction is insufficient to account for individual differences in reactivity to common allergens.

Alleles↗
PubMed1994

Discrepancies between in vitro and in vivo tests for house dust mite allergy: in domestic exposure a better predictor than sensitization?

We subjected seven asthmatic children to two bronchial allergen challenges, first with an extract from the house dust mite Dermatophagoides pteronyssinus (Der p) and then Dermatophagoides farinae (Der f), or vice versa. All children had elevated specific serum IgE to both species as well as reactions by crossed radioimmuno/electrophoresis (CRIE) to both group I and II allergens from both species. Immunoabsorption and subsequent analysis by CRIE showed a considerable concentration of serum IgE with specificity for epitopes common to the two species of house dust mite. Home dust sampling established that all children were exposed to Der f and only two to Der p. On bronchial provocation tests, all responded to Der f with an immediate reaction and five with a late reaction, only three of seven showed an immediate response to Der p, with four of the seven showing a late reaction. Our data could indicate that the local allergic immune reaction in the respiratory tract is sustained by ongoing exposure, and may thus have a different species specificity than the response reflected in the serum. In conclusion, our data indicates a lack of association between in vitro and in vivo tests for house dust mite allergy, which supports the continuing need for monitoring current clinical sensitization by allergen provocation tests and by measuring domestic exposure to the corresponding allergen. Extended studies are needed to support our findings.

Allergens↗
PubMed1994

Cat (Fel d I), dog (Can f I), and cockroach allergens in homes of asthmatic children from three climatic zones in Sweden.

We have investigated the levels of cat (Fel d I), dog (Can f I), and cockroach (Per a I) allergens in dust from bedrooms, living rooms, kitchens, and bathrooms from 123 homes of asthmatic children in three zones of Sweden with varying climates. Absolute indoor humidity (AIH), relative humidity (RH), rate of ventilation in air changes per hour (ach), and number of airborne particles were also measured. Fel d I, Can f I, and Per a I allergen contents were determined by mab ELISA, and the levels were related to various environmental factors. The major cat allergen, Fel d I, was detected in all homes, and the concentrations varied between 16 ng and 28,000 ng/g fine dust. The dog allergen, Can f I, was detected in 85% of the homes, and the levels varied from 60 ng to 866,000 ng/g dust. Cockroach allergen was detected in only one home (40 ng/g). Fel d I and Can f I allergens were equally distributed geographically. Dust from living rooms contained significantly higher (P < 0.05) concentrations of both Fel d I and Can f I allergens than dust from bedrooms, kitchens, and bathrooms. The levels tended to be higher in homes with poor ventilation (< 0.5 ach) and in homes with wall-to-wall carpets. Significantly higher (P < 0.01) numbers of airborne particles were found in homes with high humidity (i.e., AIH > or = 7 g/kg or RH > or = 45%).(ABSTRACT TRUNCATED AT 250 WORDS)

Air Conditioning↗