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Copyright of Journal of Laboratory Medicine / Laboratoriums Medizin is the property of De Gruyter and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Journal of Laboratory Medicine / Laboratoriums Medizin is the property of De Gruyter and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Serological tests for immunoglobulin G4 (IgG4) against foods are persistently promoted for the diagnosis of food-induced hypersensitivity. Since many patients believe that their symptoms are related to food ingestion without diagnostic confirmation of a causal relationship, tests for food-specific IgG4 represent a growing market. Testing for blood IgG4 against different foods is performed with large-scale screening for hundreds of food items by enzyme-linked immunosorbent assay-type and radioallergosorbent-type assays in young children, adolescents and adults. However, many serum samples show positive IgG4 results without corresponding clinical symptoms. These findings, combined with the lack of convincing evidence for histamine-releasing properties of IgG4 in humans, and lack of any controlled studies on the diagnostic value of IgG4 testing in food allergy, do not provide any basis for the hypothesis that food-specific IgG4 should be attributed with an effector role in food hypersensitivity. In contrast to the disputed beliefs, IgG4 against foods indicates that the organism has been repeatedly exposed to food components, recognized as foreign proteins by the immune system. Its presence should not be considered as a factor which induces hypersensitivity, but rather as an indicator for immunological tolerance, linked to the activity of regulatory T cells. In conclusion, food-specific IgG4 does not indicate (imminent) food allergy or intolerance, but rather a physiological response of the immune system after exposition to food components. Therefore, testing of IgG4 to foods is considered as irrelevant for the laboratory work-up of food allergy or intolerance and should not be performed in case of food-related complaints. [ABSTRACT FROM AUTHOR]

Copyright of Der Hautarzt is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Omalizumab, a recombinant monoclonal anti-immunoglobulin E (IgE) antibody, shows proven efficacy in the treatment of allergic diseases. A little is known about the immunological pathways affected by the decrease of circulating free IgE during omalizumab treatment. Aim of the study: To investigate the immunological consequence of IgE withdrawal, we studied the influence of omalizumab on stimulated IgE-release of cultured peripheral blood mononuclear cells (PBMC) and on the relative number of lymphocytes in the peripheral blood (cellular immune status) in patients with allergic asthma. Methods: Nineteen patients were enrolled and received omalizumab at a dose of at least 0.016 mg/kg/IgE (IU/ml) every 4 weeks. PBMC were isolated from peripheral blood. Cells were cultured and stimulated with IL-4 (5 ng/ml) and CD40 ligand (1 μg/ml) for 10 days. IgE release was detected in cell culture supernatants by enzyme-linked immunosorbent assay (ELISA). Cellular immune status was investigated by fluorescence-activated cell sorting. Results: Omalizumab treatment induced significant inhibition of stimulated IgE release (median 1.38-0 ng/ml vs. 1.64-2.0 ng/ml in placebo group, P < 0.05). B-lymphocyte counts were also significantly lower in the omalizumab group compared with placebo after 12 weeks of treatment (median 18.2-15.6% lymphocytes vs 12.7-13.7% lymphocytes after placebo, P < 0.01). There were no significant differences in the other lymphocyte subpopulations between the groups. Conclusions: These findings provide evidence of immunological influences of omalizumab treatment, leading to a downregulation of IgE secretion and decrease of lymphocyte subpopulations (B-cells) indicating their anti-inflammatory potency. [ABSTRACT FROM AUTHOR]

Background: Sublingual treatment of grass pollen induced rhinoconjunctivitis might provide easier access to specific immunotherapy (SIT) and minimize the risk of serious adverse events (AEs) compared to subcutaneous SIT. Aim of the study: To identify a safe dose range for once-daily administration of a grass allergen tablet in participants with grass pollen induced seasonal rhinoconjunctivitis. Methods: A randomized, double blind, placebo-controlled Phase I trial was conducted outside the grass pollen season. Seven dosage groups [25 000, 75 000, 150 000, 300 000, 500 000, 750 000, or 1 000 000 standardized quality tablet (SQ-T)], consisting of 12 participants randomized either to active treatment or placebo (3 : 1) daily for 28 days, commenced treatment in a staggered manner at intervals of approximately 1 week to allow for intermittent safety reviews. Results: The grass allergen tablet did not cause any serious, systemic or significant (leading to withdrawal) AEs. The overall incidence of AEs was 74% (1013 events); all of mild or moderate intensity and most considered treatment-related. The most frequently reported treatment-related AEs, including irritation of the throat, and itching sensations in the mouth and ears, increased with dose. These were primarily mild in intensity, started shortly after medication intake and lasted for minutes to a few hours maximum. Objective oral findings were also dose-dependent. No clinically significant observations were found in safety laboratory, vital signs and 12-lead ECG. Conclusions: A sublingual grass allergen tablet in doses up to 1 000 000 SQ-T daily caused no serious or systemic AEs displaying a safety profile that allows further investigation as once-daily self-medication. [ABSTRACT FROM AUTHOR]

Copyright of Der Hautarzt is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Thirty-nine patients sensitized to Alternaria were evaluated using titrated skin-prick test (SPT), histamine release studies (HR), inhibition of RAST and immunoblotting studies. To determine the relevance of the major allergen, Alt a I, specific rabbit antibodies against Alt a I and Alt a B were used. The antibodies were preincubated at different concentrations: (i) with the Alternaria allergen dose required for maximum response in the HR assay (10 BU/ml) and (ii) with the Alternaria antigen coupled to RAST paper discs (1000 BU/disc). Dose dependent inhibition of histamine release (n = 30, &xsline; = 80% ± 4%. IC30 = 0.69 μg/ml) and of RAST (n = 7, IC30=4.4 μg/ml) was found in all patients sensitized to Alternaria as indicated by allergen induced HR. The greater the response to Alternaria in HR, the higher the antibody concentrations necessary for inhibition (P < 0.05). Immunoblot experiments (n=25) using SDS-PAGE showed in all cases IgE- and IgG binding at approximately 28 kD, which is the size reported for the major allergen. Alt a I. In two cases, slight IgE binding at 45 and 66 kD was also found, while in two other patients, only IgE binding at 66 kD was seen. Our findings emphasize the major importance of Alt a I in patients sensitized to Alternaria. [ABSTRACT FROM AUTHOR]

A new class of phenyl (pyridylalcyl) guanidines, acting as potent histamine H-agonists, inhibits IgE-mediated human basophil histamine release in a nanomolar range. IC-level of three substitutes of this group (arpromidine, BUA-75, and FRA-19) were found to be 0.02, 0.015 and 0.008 μ M. The inhibition appeared with a fast onset (plateau after 10 min. preincubation) and claimed its maximum (60±2.9%, 63±1.8%, and 61±3.1%, n=7) with 10 μ M of the compounds. H-mediated inhibition was totally blocked by 10 μ M famotidine, a potent histamine H-antagonist. The amount of anti-IgE or antigen for the initiation of the immunological release influenced the strength of inhibition of H-agonist FRA-19 ( p<0.05). Combined preincubation of FRA-19 with zardaverine, a cAMP-specific phosphodiesterase III/IV inhibitor, produced a synergistical inhibitory effect of leukocyte histamine release, which might explained by their different sites of action on intracellular cAMP levels. The capability of histamine to inhibit its own release is mediated by H-receptors exclusively. New, potent H-receptor stimulating compounds with positive inotropic effects possess additional potent anti-allergic properties. [ABSTRACT FROM AUTHOR]

Background and objective The ELltest® is a newly developed system to measure specific IgE based on allergen bound to paper rings and an alkaline phosphatase conjugated second antibody detection system. It was compared to the CAP® system, a method based on allergen conjugated to an encapsulated cellulose polymer and a Β galactosidase conjugated fluorescence detection system. Methods Sera of 300 patients with positive history and positive skin-prick tests to common allergens (birch, timothy-grass, cat dander, dermatophagoides pteronyssinus, wasp venom) and 30 negative controls were tested in both systems. Serial dilutions of high titre sera were measured; inter and intra assay coefficients of variation (cv) were determined. Results The CAP system proved to be more sensitive (92.3%) compared to ELltest (84%) but marginally less specific (94.7% for CAP versus 96.7% for ELltest). Intraassay cv were slightly lower in the ELitest (7.2% CAP versus 6.4% ELitest), whereas the interassay cv was roughly twice as high for ELitest (20.1 %) than for the CAP system (11.4%). Linearity over an 8-fold dilution was good in both tests (r2 0.979 ELltest versus 0.996 CAP), although ELltest levelled off at higher allergen concentrations. Similarly, correlation analysis between both systems revealed that ELltest consistently measured lower values, especially at higher concentrations of specific IgE. The slope of the linear regression line of a log/log plot of measured IgE concentrations was significantly lower than 1 in birch, cat and wasp; the y-intersect was significantly lower than 0 in all analysed allergens. Conclusion These results suggest that the ELltest system for the measurement of specific IgE is not quite as reproducible and sensitive as the CAP system but slightly more specific, and that higher concentrations of specific IgE are measured lower in the ELitest. One potential reason might be that the amount of allergen bound to a paper ring might be smaller than that bound to a cellulose polymer, but further experiments are necessary to prove this hypothesis. [ABSTRACT FROM AUTHOR]

In recent years, it has been possible to demonstrate mediator release into the nasal secretion after nasal allergen challenge in patients with allergic rhinitis. Using the nasal provocation model, we determined whether the mediator release was altered in immunotherapy-treated patients. Seventeen grass-pollen-allergic patients were examined under controlled, reproducible conditions. Serial challenges with increasing doses of grass pollen produced increasing numbers of clinical symptoms and release of mediators such as kinins, TAME-esterase activity, and histamine. Ten patients received a semidepot perennial grass-pollen extract for 4 years. Seven patients served as controls and did not receive immunotherapy during the observation period. Data from the group of patients receiving immunotherapy over the first year already showed a partially significant decline in the maximal mediator release after nasal allergen challenges compared to the results of pretreated challenges, whereas controls did not show any significant changes. Nasal allergen challenges after termination of 4 years' immunotherapy significantly modified the mediator release compared to pretreatment values (TAME-esterase activity P<0.05, kinins P<0.01, and histamine P<0.01). Decrease of mediator release paralleled the symptom-medication scores and quantitative skin prick test. Finally, we could demonstrate a significant correlation between specific IgG increase and mediator decrease in the treated group. [ABSTRACT FROM AUTHOR]

Specific immunotherapy (SIT) induces immunological changes leading to a decrease in allergen-driven symptoms and medication use. However, the use of arbitrary and variable assay formats and units hampers comparisons between SIT studies. The magnitude of IgG response induced by SIT is not directly linked to clinical improvement, so an increase in allergen-specific IgG4 should be considered a necessary but not sufficient marker of clinical efficacy. Dose-dependent IgG4 immune responses should be demonstrated by the manufacturer, not by doctors. Symptom and medication scores are essential end-points for immunotherapy studies, but are subjective, so close association with objective assay measurements will be difficult. Nonetheless, blocking antibody assays combining serology and cellular function may provide a solution for relating immunological assay measurements to clinical outcomes. [ABSTRACT FROM AUTHOR]