ISSN:0954-7894    

DOI:10.1111/j.1365-2222.1996.tb00493.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

ISSN:0954-7894    

DOI:10.1111/j.1365-2222.1996.tb00494.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

ISSN:0954-7894    

DOI:10.1111/j.1365-2222.1996.tb00495.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

SummaryBackgroundRapid clinical tolerance can be induced over several hours by very fast bee venom immunotherupy (VIT) protocols.ObjectiveTo investigate the mechanisms underlying VIT we examined the changes of blood basophil responsivetiess during VIT.MethodsSeven bee venom allergic patients with a history of severe systemic reactions after a bee sting were investigated. A cumulative dose of 111.1 μg bee venom (BV) was administered sc over 3.5 h under intensive care conditions according to an ultra‐rush protocol. The release of histamine and the formation of leukotrienes in response to BV, major BV allergen Phospholipase A2(PLA), IgE receptor cross‐linking with the use of monoclonal antibodies against IgE and IgE receptor, as well as IgE independent activation in response to C5a were determinedin vitrobefore and after ultra‐rush VIT.ResultsWe demonstrated a decrease of total histamine in peripheral blood leucocytes just after VIT. Histamine release in response to all the stimuli used is not affected by ultra‐rush VIT, if expressed as per cent release of total histamine. However, the absolute amount of product released in response to stimulation was decreased, particularly with allergen (BV, PLA). We also found a significant reduction of LTC4 formation after VIT in samples stimulated with specific allergen (BV, PLA).ConclusionBlood basophils are a target for VIT, which induces impaired release of both preformed and newly generated mediators. However, we believe the basic mechanisms of rapid clinical tolerance induced by ultra‐rush VIT remain to be in

ISSN:0954-7894    

DOI:10.1111/j.1365-2222.1996.tb00496.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

SummaryBackgroundRecognition of antigen bound to the major histocompatibility complex by the T cell receptor is insufficient to lead to T cell proliferation and effector function, which require co‐stimulatory signals, such as those resulting from the interaction of CD28 expressed on T lymphocytes and CD80/CD86 expressed on APCs. Lack of interaction between these accessory molecules during antigen stimulation leads to a state of antigen‐specific lymphocyte unresponsiveness. Previous studies have shown that rush venom immunotherapy decreases venom‐specific T cell proliferation very early after the initiation of the rush.ObjectiveIn order to see whether this hyporeactivity was associated with a down regulation of accessory molecules, we studied CD28 surface expression on T lymphocytes from 10 non‐atopic controls and from 10 non‐atopic patients undergoing rush venom immunotherapy.MethodsPeripheral blood samples were collected before the rush (day 0), at the end of the rush (day 1), at day 15 and at day 45. CD28 expression was analysed using flow cytometry with double labelling of the CD4+and CD8+lymphocyte subpopulations.ResultsAt baseline CD28 was expressed at a higher level on T lymphocytes from allergic patients than from control subjects (P<0.04), and in particular on the CD8 subset (P<0.01), reflecting a decrease in the suppressive CD8+CD28–subpopulation. No changes were found in the percentages of total CD28+T cells, CD4+CD28+or CD8+CD28+cells at the different time points after the initiation of immunotherapy.ConclusionThese results suggest that the CD28 pathway is probably involved in the development of allergic reactions, but at least at the phenotypic level, CD28 expression remained unchanged after rush venom im

ISSN:0954-7894    

DOI:10.1111/j.1365-2222.1996.tb00497.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

SummaryBackgroundThe 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.ObjectiveTwo sets of trials were performed in order to investigate changes of local and systemic eosinophil activity and their possible link with symptoms and hyper‐reactivity in the allergic LPR in the eye.MethodsIn 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 48h previously was tested in nine sensitized individuals.ResultsIn 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 48h after an allergen challenge was not confirmed.ConclusionECP 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

ISSN:0954-7894    

DOI:10.1111/j.1365-2222.1996.tb00498.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

SummaryBackgroundMeasurement of markers of eosinophil activation in asthmatics provides information indicative of ongoing inflammatory processes in the airways.ObjectivesThis study was eonducted to determine the correlations between serum markers of allergie inflammation with spirometry parameters in asthmatic children in different treatment groups.MethodsBlood eosinophils. serum levels of eosinophil cationic protein (ECP). eosinophil protein X (EPX), myeloperoxidase (MPO) and tryptase were measured simultaneously with serial measurements of FEV1/FVC, FEF25–75and FEF in 60 children with acute asthma on admission and after 2, 14, 30 and 60 days. Group A received bronchodilators only (n= 20). group B received sodium cromoglycate (SCG) (n= 20) and group C received oral and/or inhaled corticosteroids (n= 20).ResultsOral steroid treatment (2 mg /kg/day). given at the onset of the asthma attack, resulted in significant reduction in the ECP and EPX levels in all the children. However, these reduced ECP and EPX levels were not sustained in the children, even in those who continued on maintenance steroid treatment. Significant, but inconsistent, correlations between ECP, EPX with total eosinophil count, percentage eosinophils and spirometry parameters were observed at the different time‐points. Tryptase levels were normal in all subjects. There were no significant correlations between myeloperoxidase levels and the spirometry parameters or eosinophil parameters. Serial monitoring of ECP and EPX levels was found to be of some use in predicting clinical outcome in certain steroid‐dependent asthmatics (group C) but of no value in the mild asthmatics (group A).ConclusionWhile elevation of ECP, EPX and MPO in the serum of childhood asthmatics suggests ongoing inflammation and may inversely correlate with spirometry parameters in some patients, the relationship between these markers and airway function is not a simpl

ISSN:0954-7894    

DOI:10.1111/j.1365-2222.1996.tb00499.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

SummaryBackgroundHLA class II genetic polymorphism has been variably implicated in susceptibility to specific immune responsiveness to house dust mite (HDM) allergens, and may also influence the development of atopy.ObjectiveIn order to assess accurately the influence of HLA alleles in the atopic immune response, we typed 22 families selected from 131 previously obtained randomly selected families (i.e. without regard to atopy or asthma), chosen on the basis of two or more members having skin prick reactivity to HDM.MethodsEach individual was fully typed for HLA‐DRB1, DQA1, DQB1 and DPB1 class II alleles using a combination of sequence‐specific oligonucleotide probes (SSOP) and sequence‐specific primer (SSP) polymerase chain reaction (PCR) typing and direct sequencing.ResultsUsing appropriate statistical tests, no significant allelic associations were found between any DRBl, DQB1 or DPBl alleles and atopy or skin prick reactivity toDermataphagoides pteronyssinus(Der p) orD. farinae(Der f). However, positive associations were found between DQA 1*0301 and skin prick reactivity to Der f (P= 0.009) and atopy (P= 0.027). Sib‐pair analysis revealed no significant sharing of alleles between affected sib pairs for any of the phenotypes studied.ConclusionThese results fail to confirm a previously reported association between the DRB1*04 and 07 haplotypes and atopy, and suggest that HLA class II restriction does not play a major role in the development of the IgE response to domestic house dust mite allergens in the British pop

ISSN:0954-7894    

DOI:10.1111/j.1365-2222.1996.tb00500.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

SummaryBackgroundThe allergen Der p 6 fromDermatophagoides pteronyssinushas been described by substrate affinity as mite chymotrypsin.ObjectiveThe aim of this paper was to describe a cDNA clone encoding the allergen.MethodscDNA was cloned from a λ library using oligonucleotides published for Der p 6.ResultsThe clone P6.1.1 had the N‐terminal amino acid residues as reported for Der p 6, and at position 189 the Ser was conserved in chymotrypsin for substrate specificity as well as the catalytic triad of His57, Asp102 and Ser195 for serine proteases. The estimated Mr was 24.9K and it was 37% identical to the trypsin allergen Der p 3.ConclusioncDNA encoding Der p 6 has been describ

ISSN:0954-7894    

DOI:10.1111/j.1365-2222.1996.tb00501.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

SummaryBackgroundAdverse reactions, including immediate hypersensitivity, to the widely used antibacterial agent trimethoprim occur quite frequently. In recent years some progress has been made in developing an immunoassay to aid diagnosis of type 1 allergic reactions to trimethoprim and to define the basis of IgE antibody recognition of the drug.ObjectivesThe molecular basis of IgE binding to trimethoprim was examined more closely with a view to defining the fine structural recognition differences between patients' sera. Utilization of such information may lead to immunoassays that are more specific and sensitive and of greater diagnostic value.MethodsImmunoassays for specific IgE antibodies and quantitative hapten inhibition studies with trimethroprim and selected structural analogues were employed, together with sera from eight subjects clearly defined clinically as allergic to trimethoprim.ResultsThree different allergenic determinant structures have been identified on the trimethoprim molecule. Identification of the 3,4‐dimethoxybenzyl group as a determinant was achieved on the basis of inhibitory activities of diaveridine, 3,4‐dimethoxy‐phenylethylamine, 3,4‐dimethoxybenzoic acid and 3,4,5‐trimethoxycinnamic acid. Evidence that the opposite end of the trimethoprim molecule was not being recognized was obtained from results with some pyrimidine derivatives, each of which showed no activity. Identification of the second determinant, the 2,4‐diamino‐5‐(3′,4′‐dimethoxybenzyl) pyrimidine group, rested mainly on the superior inhibitory potency of diaveridine, which differs from trimethoprim by just one methoxy group. With sera from some trimethoprim‐allergic subjects, only trimethoprim was active, suggesting that the entire molecule was a third IgE‐binding determinant structure.ConclusionAs with other drug allergenic determinants defined so far, heterogeneity of trimethoprim IgE‐binding determinants exists, and fine structural differences between determinants may be as small as a single methoxy group. Identification of the 2,4‐diamino‐5‐(3′,4′‐dimethoxybenzyl) pyrimidine group as an allergenic determinant increases the number of known trimethoprim determinants to three, and suggests that the number and heterogeneity of determinants will be a reflection of

ISSN:0954-7894    

DOI:10.1111/j.1365-2222.1996.tb00502.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY