Abstract

BackgroundAsthma is increasing worldwide and results from a complex immunological interaction between genetic susceptibility and environmental factors. Autovaccination with E. coli induces a strong TH-1 immune response, thus offering an option for the treatment of allergic diseases.MethodsProspective open trial on safety, tolerability, and impact on allergic inflammation of an autologous E.coli autovaccine in intermittent or mild persistent house dust mite asthma. Determination of exhaled nitric monoxide (eNO) before and after bronchial mite challenge initially and after nine months of autovaccination.ResultsIn nine subjects and a total of 306 injections, we observed 101 episodes of local erythema (33.3%; median of maximal diameter 2.5 cm), 95 episodes of local swelling (31.1%; median of maximal diameter 3 cm), and 27 episodes of local pain (8.8%). Four subjects reported itching at the injection site with a total of 30 episodes (9.8%). Median eNO increase after autovaccination was significantly smaller (from 27.3 to 33.8 ppb; p = 0.334) compared to initial values (from 32.6 to 42.2 ppb; p = 0.046) (p = 0.034). We observed no serious adverse events. All organ functions (inclusive electrocardiogramm) and laboratory testing of the blood (clinical chemistry, hematology) and the urine (screening test, Β-microglobuline) were within normal limits. Vital signs undulated within the physiological variability.ConclusionThe administration of autologous autovacine for the treatment of house dust mite asthma resulted in a reduction of the eNO increase upon bronchial mite challenge. In nine subjects and 306 injections, only a few mild local reactions and no systemic severe adverse events were observed.Trial registrationEudraCT Nr. 2005-005534-12ClinicalTrials.gov ID NCT00677209

Highlights

  • Asthma is increasing worldwide and results from a complex immunological interaction between genetic susceptibility and environmental factors

  • Neutralization tests of cytokine activity revealed that the T-cell-suppression in specific immunotherapy and immunotolerance against mucosal antigens is induced by IL-10 and TGF-ß

  • Eight subjects completed the study with 100% adherence to all visits; one subject (No 2) dropped out due to urticaria, which had been observed before the study started

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Summary

Introduction

Asthma is increasing worldwide and results from a complex immunological interaction between genetic susceptibility and environmental factors. Autovaccination with E. coli induces a strong TH-1 immune response, offering an option for the treatment of allergic diseases. Autovaccination with E. coli induces in animal models and in human studies a strong TH-1 immune response. In allergic individuals, this immunization can cause a shift from TH-2- to TH-1dominated immune response, and has the potential to Allergic diseases such as rhinoconjunctivitis or bronchial asthma are a major burden of disease, requiring evidence-based therapy concepts. In immunotolerance towards house dust mite, an allergenspecific T-cell suppression directed against the house dust mite allergen Der p1 is observed In allergics, this TH1 (IFN-y)-immunresponse is reduced, with a shift towards a TH2-dominated (IL-5, IL-13) immune pattern. That depending on the age and individual features of house dust mite allergics, SIT is of heterogeneous efficiency [3], demanding even more therapeutic alternatives

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