[IgE-mediated allergic airway diseases].
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Asthma↗
Biomedical subjects
J Kleine-Tebbe
Publications and source records attributed to J Kleine-Tebbe.
[Current recommendations for the use of SCIT and SLIT].
Allergen specific immunotherapy (SIT) is the only potentially curative treatment of IgE mediated allergic diseases. To ensure its effective use, many requirements must be met before and during therapy. Before starting immunotherapy, informed consent should be obtained, along with the consideration of the indications and contraindications. SIT should be prescribed and administered only by physicians with experience in allergic disease who are qualified to manage severe anaphylactic reactions. The clinical symptoms and the age of the patients determine the route of application, choice of allergen extracts and the duration of treatment. Numerous products and protocols facilitate an individualised therapy.
Desensitization, Immunologic↗
Safety of a SQ-standardised grass allergen tablet for sublingual immunotherapy: a randomized, placebo-controlled trial.
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% (1,013 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.
Administration, Sublingual↗
Omalizumab decreased IgE-release and induced changes in cellular immunity in patients with allergic asthma.
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 microg/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.
Adult↗
[Specific immunotherapy in allergic asthma].
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Allergens↗
[Cross-reactive allergen clusters in pollen-associated food allergy].
Immediate symptoms caused by allergens without previous primary sensitization are commonly based on cross-reactive IgE antibodies. They are responsible for pollen-associated food allergies, i.e., fruit allergy in cases of birch pollen allergy or allergy to celery and spices in cases of mugwort pollen allergy. Similar structures between the major allergen of birch pollen (Bet v 1) and a variety of pathogenesis-related proteins from the same family (PR-10), abundant in hazelnuts, fruits, and vegetables, have been well established. Other candidates are profilins, ubiquitous panallergens with little clinical relevance, and stable lipid transfer proteins, responsible for systemic reactions predominantly in Mediterranean countries. Depending on stability, dose, and resorption of these proteins, clinical symptoms are limited to the oro-pharyngeal cavity or develop systemically far from the site of allergen exposure. Clinical diagnosis is based on a positive case history with corresponding allergic sensitization to pollen allergens. Targeted skin testing with native products (i.e., prick to prick test with fresh fruits) appears to be superior for unstable allergens compared to commercial extracts. Individuals should be familiar with cross-reactive patterns; however, allergen avoidance is only recommended in cases of clinical symptoms.
Allergens↗
[Allergen immunotherapy - a position paper of the German society for allergology and clinical immunology].
Mechanisms of allergen immunotherapy (AIT) are complex inducing numerous immunological effects. Successful AIT is most likely based on a functional switch of and tolerance induction in specific T cells downregulating allergic hypersensitivity and inflammation. Subcutaneous AIT for allergic rhinoconjunctivitis and allergic asthma has been successfully assessed in controlled studies with several clinically important allergens (i. e. birch-, grass- and mugwortpollen, dust mites, animal dander) and has shown convincing clinical efficacy. Considered as the only causal treatment besides allergen avoidance at present, AIT can alter the natural course of allergic diseases. Hymenopteravenom hypersensitivity (to bee- and wasp venom) treated with AIT gives the best results compared to AIT with other allergens. AIT is indicated in patients with IgE-mediated sensitizations and corresponding clinical symptoms to allergens, which do not or hardly permit allergen avoidance and which are available as suitable extracts. Decisions about indication and allergen selection should only be made by a physician with certified training or qualified knowledge and skills in allergology. AIT is administered by physicians experienced in this therapy. After addressing tolerability and present status of health the recommended or individually adjusted does is injected and precisely documented, followed by a mandatory waiting period of 30 minutes. Indication for and application of AIT in children are quite similar compared to the treatment of adults. Children tolerate AIT very well and benefit especially from its immunomodulatory effects. Risk factors for and results of unwanted systemic effects can effectively be minimized by training of the staff members involved, adhering to safety standards and immediate emergency treatment. Modified allergens, recombinant proteins and immunomodulatory adjuvants created by basic research are promises for an improved efficacy of AIT with reduced unwanted effects in the future.
Allergens↗
Immunoblot studies in birch pollen-allergic patients with and without fruit hypersensitivity: part I: antibody pattern for birch pollen extract.
About 40-70% of birch pollen allergic patients show allergic symptoms after ingesting or handling raw fruits. Several investigations have indicated a partial immunological identity between birch pollen and stone fruit. To further clarify this association, we investigated 59 patients with allergic symptoms (conjunctivitis, rhinitis, and asthma during the birch pollen season) and 18 nonatopic controls by skin prick test (SPT) and RAST with birch pollen, fresh apple, cherry, and peach as well as freshly prepared fruit extracts. According to a questionnaire dealing with symptoms after ingestion of raw fruits, the subjects were divided into groups with (35 FH+) and without (24 FH-) fruit hypersensitivity. IgE, IgG, IgG1, IgG4, IgA, and IgM binding patterns to birch pollen extracts were performed with 33 sera (12 FH+, 11 FH-, and 10 nonatopic controls) using the immunoblot-technique. Patients with FH+ expressed a significantly stronger sensitization to birch pollen than patients without FH-, as measured by RAST and SPT. Native fruits induced stronger SPT reactions than fruit extracts, and patients with FH+ showed a significantly higher skin index with all fruits and fruit extracts tested. Specific IgE, IgG, IgG1, IgG4, IgM and IgA to birch pollen extracts could be detected by immunoblot in all groups, albeit with different frequencies and intensities. From this data we conclude that fruit hypersensitivity is related more to the 17 kd and 67-85 kd than to the 26-28 kd or 36 kd protein bands of the birch pollen extract. The relationship of specific IgE > IgG > IgM to a single protein band seems to be associated with the development of symptomatic type I allergy.
Adolescent↗
Immunoblot studies in birch pollen-allergic patients with and without fruit hypersensitivity: part II: antibody pattern for fruit extracts.
Patients allergic to birch pollen also exhibit more hypersensitivity reactions to fresh fruits and vegetables than do patients allergic to other pollens. Several investigations have indicated a possible partial immunological identity between birch pollen and fruits. To study this, 23 birch pollen-allergic patients 12 with (FH+) and 11 without (FH-) fruit hypersensitivity and 10 nonatopic controls were examined with self-prepared apple-peel, cherry, and peach extracts by immunoblotting. The self-prepared extracts were characterized by histamine release studies with 20 FH+ birch pollen-allergic patients. Specific IgE, IgG, IgG1, IgG4, IgA, and IgM binding patterns of the fruit extracts presented an individual distribution with at least 1-3 IgE bands at varying molecular weight locations. The FH+ group expressed intense IgE binding to the different extracts compared to the FH- group, and even the control group showed all immunoglobulin classes, though different frequencies and intensities compared to the allergic groups. It seemed that the specific IgE > IgG > IgM relation to a single antigen is important for distinguishing between symptomatic and asymptomatic persons. With this hypothesis we found most IgE with less IgG binding to apple-peel in the region of 22-28 kd and 43-56 kd, cherry: 15-25 kd and 72- > 90 kd and peach 35-41 kd and 66-76 kd, suggesting that these proteins might be important for cross-reactivity with birch pollen and developing fruit hypersensitivity.
Antibodies↗
Anaphylaxis after Argas reflexus bite.
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Adult↗
Bullous contact dermatitis from nasturtium.
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Aged↗
Protein contact dermatitis induced by isolated delayed-type hypersensitivity to meat proteins.
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Adolescent↗
[Food incompatibilities].
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Acneiform Eruptions↗
Multiple IgE-mediated sensitizations to enzymes after occupational exposure: evaluation by skin prick test, RAST, and immunoblot.
We investigated 10 sensitized and 10 nonsensitized workers from a pharmaceutic factory who had been exposed to powdered trypsin, chymotrypsin, bromelain, papain, amylase, and lipase. Ten nonallergic subjects served as a control group. Titrated skin prick tests (SPT), RAST, and immunoblot studies were performed with all six enzymes. SPT reactivity revealed multiple sensitizations to proteolytic enzymes, i.e., papain (specifically sensitized/total number of sensitizations: 9/10), trypsin (8/10), chymotrypsin (8/10), and bromelain (7/10) and appeared to be more frequent and more pronounced than sensitizations to amylase (3/10) or lipase (3/10). The low molecular weight of proteolytic enzymes (20-30 kDa) and their biologic activity might facilitate mucosal penetration more easily and thus-compared to amylase and lipase-permit an immune response and induction of allergic hypersensitivity. Immunoblot studies demonstrated IgG-binding bands in both SPT-positive and -negative workers, indicating exposure to the enzymes, but not in 10 unexposed control subjects. IgE-binding bands of the enzymes were detected only in workers with a positive SPT reaction and/or a positive RAST result. IgG bands were more frequent and the IgG/IgE ratio was increased in workers without allergic complaints compared to symptomatic workers. This might indicate that high levels of specific IgG antibodies to enzymes are associated with an immune response lacking allergic manifestations in spite of IgE-mediated sensitizations to the enzymes. Atopic subjects were at greater risk of developing IgE-mediated sensitization (7/10) and allergic symptoms to enzymes (5/7). However, even without risk of atopy, IgE-mediated hypersensitivity occurred in a few subjects (3/13) exposed to enzymes by inhalation for prolonged periods of time.
Case-Control Studies↗
Substance P enhances antigen-evoked mediator release from human nasal mucosa.
Exogenous substance P (10-80 nmol/ml) induced a dose-dependent increase in nasal symptoms in asymptomatic allergics with rhinitis (n = 15) and controls (n = 8), but did not release any mediators. However, comparing the antigen-evoked release of mediators into nasal secretions with that of a substance P-pretreated antigen challenge, we found a significant enhancement of kinins, TAME esterase activity (p < 0.05-0.01), and histamine (p < 0.001, NS) 10-20 min after antigen challenge. These results suggest 1) that substance P-induced increase in nasal congestion is mediated through direct neurokinin receptor activation independently of mast cell activation, and 2) that during the allergic reaction there is a substance P-mast cell interaction that enhances the mediator response to nasal allergen challenge.
Adult↗
Lectins do not distinguish between heterogenous IgE molecules as defined by differential activity of an IgE-dependent histamine releasing factor.
It has been suggested that differential histamine-releasing activity of an IgE-dependent histamine-releasing factor (HRF), which has recently been cloned, is related to carbohydrate difference in the IgE molecule. Lectins are able to recognize specific glycoforms and might therefore be useful in characterizing the proposed heterogeneity of IgE molecules. As one test of this hypothesis, we examined the histamine release potency of several well-characterized lectins on basophils passively sensitized with serum containing IgE molecules that support HRF-induced histamine release (IgE+) or serum that does not support release by this stimulus (IgE-). Histamine release was induced by challenging basophils with different concentrations of concanavalin A, Lens culinaris (LcH), and Pisum sativum (PSA). Dose-response curves revealed that LcH caused 30% histamine release at 2 micrograms/ml with IgE+ sensitized cells, whereas the same release with IgE- cells required sixfold higher concentrations. Similar values for PSA showed a sevenfold difference. With concanavalin A, the selectivity was reversed in that it was fourfold more active on IgE- -sensitized cells. Another pair of sera (IgE+ vs IgE-) revealed the same result for concanavalin A, but no difference occurred in LcH and PSA induced release between the IgE+ - and IgE- -sensitized cells. These contrasting findings with different pairs of IgE+ -and IgE- -containing sera indicated that the lectins LcH and PSA are not able to discriminate between IgE+ -and IgE- -sensitized cells as does HRF and therefore cannot be used to further define the proposed heterogeneity of IgE. this conclusion was supported by experiments in which basophil preparations from donors possessing natural sensitivity or insensitivity to HRF (having IgE+ or IgE- on their surface) were examined fro their response to these lectins. No difference was found in the sensitivity of the cells to challenge with LcH or PSA, and the response to concanavalin A was the opposite of that found when passively sensitized cells were used (30% histamine release at 0.9 vs 3.5 micrograms/ml for IgE+ vs IgE- donors, respectively). We conclude that oligosaccharide-specific lectins do not differentiate between HRF-reactive and HRF-nonreactive IgE molecules on basophils.
Basophils↗
Clonal diversity of IL-4 and IL-13 expression in human allergen-specific T lymphocytes.
The expression of IL-4 and IL-13 was analyzed in a panel of short ragweed allergen (Amb a 1)-specific T-cell clones from an allergic subject and a nonallergic individual. The T cells from the allergic subject showed a predominantly TH0 phenotype. The T cells from the nonallergic individual produced undetectable levels of IL-4 and high level of interferon-gamma, suggesting a TH1 cytokine profile. However, all T-cell clones showed significantly higher levels of IL-13 secretion than IL-4 secretion, and no quantitative correlation could be found between the levels of IL-4 and IL-13 in the clones tested. Furthermore, both cytokines showed similar kinetics of expression in antigen-induced steady-state messenger RNA. Finally, both cytokines were induced by stimulation of the cells with either ionomycin alone or with a combination of ionomycin and phorbol myristate acetate. These results demonstrate that there is a significant clonal diversity and quantitative difference in the levels of IL-4 and IL-13 expression in allergen-specific human T cells.
Allergens↗
Mediator release is altered in immunotherapy-treated patients: a 4-year study.
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.
Adolescent↗