Pollen Immunotherapy Research Articles

The relevance of patient‐reported outcomes in a grass pollen immunotherapy trial in children and adolescents with rhinoconjunctivitis

Patient-reported outcomes (PROs) are the only instruments available to assess the efficacy of an intervention in patients with allergic rhinoconjunctivitis. As allergic rhinoconjunctivitis is a systemic disease, it is now recommended to use not only PROs focusing at classical symptoms, but also health-related quality of life (HRQL) instruments in immunotherapy trials. A previously published immunotherapy trial in children and adolescents (6-18 yr) with hay fever provided us with data to assess the relevance of two of these additional outcome measures, the disease-specific rhinoconjunctivitis quality of life questionnaire (RQLQ) and the generic COOP/WONCA-charts (CWC). A PRO was considered relevant if it was responsive to pollen exposure and at least had a moderate correlation with the classical symptoms of allergic rhinoconjunctivitis. Furthermore, we evaluated a post-season PRO, that is, a global assessment of symptoms (GAS). This assessment is used in clinical trials as a tool for selecting participants with sufficient symptoms and in daily practice to evaluate the patient's complaints during the preceding season. We assessed the correlation of this retrospective score with the actual symptoms during the previous pollen season. Data from 36 children and 63 adolescents were analysed. On the basis of the total scores of the paediatric and adolescent version of the RQLQ, both questionnaires were considered relevant as they were responsive to exposure and showed a moderate to strong correlation with the rhinoconjunctivitis symptoms. However, in both children and adolescents, 40% of the RQLQ items were not relevant according to our definition. The CWC as a whole and the separate charts appear less relevant because of the weak correlations with the daily symptom score from the diary. The correlation between our post-season GAS and the in season daily symptom score was weak. The paediatric and adolescent RQLQ are relevant, but could be shortened as they contain a substantial number of irrelevant items. The CWC are not relevant in the monitoring of children and adolescents with allergic rhinoconjunctivitis caused by grass pollen. The retrospective GAS does not sufficiently reflect the actual symptoms during the preceding season.

Cross‐reactive antigens for natural IgE antibodies: allergens with the potential to transform a dormant to an active allergic response?

Cross‐reactive antigens for natural IgE antibodies: allergens with the potential to transform a dormant to an active allergic response?

Hypoallergenic Mutants of the Timothy Grass Pollen Allergen Phl p 5 Generated by Proline Mutations

Background: Phl p 5 is a major allergen of Timothy grass (Phleum pratense). A recombinant native Phl p 5 has already been used in clinical trials of allergen-specific immunotherapy as a component of a cocktail of allergens. Recombinant hypoallergenic allergens should further improve the treatment by reducing the risk of anaphylactic reactions at an increased therapeutic dosage. Native Phl p 5 is formed by α-helical regions separated by regions containing prolines. In order to generate hypoallergenic mutants, we studied the effect of proline mutations in single and multiple regions. Methods: All mutants were analyzed by IgE inhibition assays and size exclusion chromatography with on-line mass determination. Selected mutants were additionally analyzed by field-flow fractionation, dynamic light scattering, circular dichroism spectroscopy, basophil activation and T-cell proliferation assays. Results: Variants lacking prolines in a single region were obtained as soluble monomers. Six of eight molecules showed a slightly reduced IgE-binding capacity. Mutants carrying proline deletions in multiple regions formed monomers, dimers or insoluble aggregates. The mutant MPV.7 with five proline deletions and a substitution of proline 211 to leucine is monomeric, shows a strongly diminished IgE binding and maintains T-cell reactivity. The hydrodynamic radius and the content of the α-helical structure of MPV.7 are well comparable with the wild-type allergen. Conclusions: The hypoallergenic Phl p 5 variant MPV.7 combines multiple proline deletions with a substitution of proline 211 to leucine and meets basic demands for a pharmaceutical application. MPV.7 is a promising candidate for grass pollen immunotherapy with a cocktail of recombinant hypoallergens.

Allergen specificity of IgG4-expressing B cells in patients with grass pollen allergy undergoing immunotherapy

Serum IgG(4) responses to allergen immunotherapy are well documented as blocking allergen binding to receptor-bound IgE on antigen-presenting cells and effector cells, but the molecular characteristics of treatment-induced IgG(4), particularly in relation to expressed antibody, are poorly defined. We aimed to clone and express recombinant IgG(4) from patients receiving grass pollen immunotherapy using single B cells to obtain matched heavy- and light-chain pairs. IgG(4)(+) B cells were enriched from blood samples taken from 5 patients receiving grass pollen immunotherapy. Matched heavy- and light-chain variable-region sequences were amplified from single IgG(4)(+) B cells. Variable regions were cloned and expressed as recombinant IgG(4). Binding analysis of grass pollen-specific IgG(4) was performed by using surface plasmon resonance. Functional assays were used to determine IgE blocking activity. In a separate experiment grass pollen-specific antibodies were depleted from serum samples to determine the proportion of grass pollen-specific IgG(4) within total IgG(4). Depletion of grass pollen-specific antibodies from serum led to a modest reduction in total IgG(4) levels. Matched heavy- and light-chain sequences were cloned from single IgG(4)(+) B cells and expressed as recombinant IgG(4). We identified an IgG(4) that binds with extremely high affinity to the grass pollen allergen Phl p 7. Furthermore, we found that a single specific mAb can block IgE-mediated facilitated allergen presentation, as well as IgE-mediated basophil activation. Although increases in IgG(4) levels cannot be wholly accounted for within the allergen-specific fraction, allergen immunotherapy might result in the production of high-affinity allergen-specific blocking IgG(4).

The role of seasonal grass pollen on childhood asthma emergency department presentations

Few studies have focused on the role of grass pollen on asthma emergency department (ED) presentations among children. None have examined whether a dose-response effect exists between grass pollen levels and these asthma exacerbations. To examine the association between increasing ambient levels of grass pollen and asthma ED presentations in children. To determine whether these associations are seen only after a thunderstorm, or whether grass pollen levels have a consistent influence on childhood asthma ED visits during the season. A short time series ecological study was conducted for asthma presentations to ED among children in Melbourne, Victoria, and grass pollen, meteorological and air quality measurements recorded during the selected 2003 period. A semi-parametric Poisson regression model was used to examine dose-response associations between daily grass pollen levels and mean daily ED attendance for asthma. A smoothed plot suggested a dose-response association. As ambient grass pollen increased to about 19 grains/m(3) , the same day risk of childhood ED presentations also increased linearly (P < 0.001). Grass pollen levels were also associated with an increased risk in asthma ED presentations on the following day (lag 1, P < 0.001). This is the first study to establish a clear relationship between increased risk of childhood asthma ED attendance and levels of ambient grass pollen below 20 grains/m(3) , independent of any impact of thunderstorm-associated asthma. These findings have important implications for patient care, such as asthma management programs that notify the general public regarding periods of high grass pollen exposure, as well as defining the timing of initiation of pollen immunotherapy.

97 Grass Pollen Allergen-induced Surface Expression of CD203C, CD63 and CD107A on CRTH2+ Basophils

BackgroundGrass pollen immunotherapy is associated with reduction in symptoms, the need for rescue medication and improvement of quality of life in patients with severe seasonal pollinosis. Although, the suppression of the early allergic response following in vivo cutaneous allergen challenge is associated with inhibition of basophil histamine release, the effects of immunotherapy on basophil reactivity is yet to be fully determined. We hypothesized that basophil reactivity as measured by increased expression of surface activation markers CD203c, CD63 and CD107a on CRTH2+ basophils is increased in grass pollen allergic individuals following in vitro allergen stimulation. We further hypothesized that this hypereactivity is reduced in immunotherapy-treated patients.MethodsHeparinized blood obtained from grass pollen allergics (n = 7), immunotherapy treated patients (n = 6) and non-atopic controls (n = 9) was incubated with 0, 0.1, 1, 10 and 100 ng/mL of P. Pratense extract at 37°C for 15 minutes. Cells were stained with anti-CD3, CRTh2, CD123, CD303, CD203c, CD63 and CD107a. Additionally, whole blood basophil histamine release was measured pre/post immunotherapy by ELISA (n = 6).ResultsA dose-dependent increase in the proportion of CD203c+, CD63+ and CD107a+ CRTH2+ basophils was observed following in vitro grass pollen stimulation in allergics but not in non-atopic controls. At 100 ng/mL of P. Pratense extract, CD203c+, CD63+ and CD107a+CRTH2+ basophils were significantly elevated in allergics compare to non-topics (P < 0.001, P < 0.001 and P < 0.009). This increase in CD203c+, CD63+CRTH2+ basophils in allergic individuals significantly correlated with timothy-specific IgE (r = 0.84, P < 0.0001; r = 0.85, P < 0.0001). Interestingly, 10- to 100-fold more allergen was required for CRTH2+ basophils to express CD203c, CD63 and CD107a in immunotherapy-treated patients compare to grass pollen allergics. At suboptimal allergen-concentration (10 ng/mL), CD203c+, CD63+ and CD107a+CRTH2+ basophils were significantly reduced in immunotherapy treated subjects compare to allergics (P < 0.001, P < 0.001 and P < 0.002). Basophil histamine release measured after treatment was significantly reduced compared to pre-treatment levels (P < 0.03).ConclusionsBasophil reactivity and histamine release is significantly reduced following grass pollen immunotherapy. The use of surface activation markers CD203c, CD63 and CD107a on basophils for monitoring clinical efficacy requires further investigations.

Profilin as an Aeroallergen by Means of Conjunctival Allergen Challenge with Purified Date Palm Profilin

Background: The role of profilin as a food allergen is well established, but little research has been done about its ability to elicit respiratory disease. Profilin is considered more of a confounding allergen on skin testing with whole pollen extracts than other airborne allergens. Our aim was to find out whether or not profilin can cause symptoms in sensitized individuals, which would be compatible with its role as an airborne allergen. Methods: We performed conjunctival allergen challenges with date palm profilin in a series of consecutive pollen-allergic patients with rhino-conjunctivitis, divided in two groups: profilin sensitized (n = 17) and not sensitized (n = 14), who served as controls. We investigated the possible association between profilin sensitization and profilin allergy in these groups of patients. Results: None of the patients from the not profilin-sensitized group had a positive result in conjunctival allergen challenges. In contrast, 65% of profilin sensitized patients had a positive conjunctival allergen challenge and were considered allergic to profilin. We found a significant statistical association between being profilin allergic and being profilin sensitized (χ² = 10.39, p < 0.005). Conclusions: Profilin seems to work as an aeroallergen in a significant proportion of profilin-sensitized patients. This might explain the uselessness of conjunctival challenges with whole pollen extracts to disclose genuine sensitization. In the future, the possibility of quantifying this allergen in pollen immunotherapy vaccines should be considered.

A randomized placebo‐controlled trial of rush preseasonal depigmented polymerized grass pollen immunotherapy*

Specific subcutaneous immunotherapy (SCIT) for seasonal rhinoconjunctivitis with unmodified allergen extracts is effective, but limited by risk of side-effects and involves treatment over 3 years. We examined a depigmented polymerized grass pollen extract for immunogenicity and for clinical efficacy in a rush preseasonal regimen. Depigmented polymerized grass pollen extract was tested for proliferation and cytokine production by peripheral blood mononuclear cells. A prospective, double-blind, placebo-controlled trial of 195 grass pollen allergic patients treated with preseasonal rush immunotherapy using depigmented polymerized allergenic extract of mixed grass pollen was performed over 2 years. Primary outcome was combined symptom and medication score (SMS) during the peak of the second grass pollen season. Secondary outcomes included combined score over the whole season, during the first grass pollen season, individual symptom and medication scores, quality of life, well days/hell days and responder analysis. Adverse events were classified using the EAACI scale. Grass pollen-specific IgE and IgG4 were measured before and during treatment. Depigmented polymerized extract stimulated dose-dependent T-cell proliferation and cytokine production. Patients treated with preseasonal SCIT showed improved combined scores during peak season at year 2 (median 3.93, interquartile range 0.77-6.27 vs median 5.86 for placebo, 3.11-8.36, P < 0.01). Most secondary outcomes were significantly better for active treatment. Side-effects were minimal, with no grade 3 or 4 reactions. Depigmented polymerized grass pollen extract is immunogenic and clinically effective in rush preseasonal SCIT. This form of immunotherapy may be an attractive option for some patients.

Functional rather than immunoreactive levels of IgG4 correlate closely with clinical response to grass pollen immunotherapy

Induction of allergen-specific IgG(4) antibodies is the most consistent immunological finding in immunotherapy trials. However, quantitative assessments of IgG(4) antibodies have not proven beneficial in evaluating clinical changes during or after immunotherapy. In the current study, we investigated the relationship between clinical outcome and allergen-specific IgG(4) titres or functional antibody responses following immunotherapy. We hypothesized that functional assays of serum IgG-associated inhibitory activity such as inhibition of IgE-allergen interactions (IgE-blocking factor) and inhibition of CD23-dependent IgE-facilitated allergen binding (IgE-FAB) correlate more closely with clinical outcome and may be biomarkers of clinical response. In an 8-month dose-response randomized double-blind placebo-controlled study, 221 polysensitized subjects with severe seasonal rhinitis received Alutard SQ, Phleum pratense 100,000 SQ-U, 10,000 SQ-U or placebo injections. Serum specimens were collected before treatment, after up-dosing, during the peak season and at the end of the study. Allergen-specific IgG(4) titres and IgG-associated inhibitory activity were evaluated. A time- and dose-dependent increase in serum inhibitory activity for both the IgE-blocking factor and IgE-FAB was observed, which paralleled increases in grass pollen-specific IgG(4) antibodies. A modest but significant inverse relationship was demonstrated between postimmunotherapy serum inhibitory activity and combined symptom-rescue medication scores (IgE-FAB: r = -0.25, P = 0.0002; IgE-blocking factor: r = -0.28, P < 0.0001), whereas this was not observed for immunoreactive IgG(4) levels (r = -0.11, P = 0.12). Functional assays of inhibitory IgG(4) and IgE-blocking factor may be more useful surrogates of clinical response than IgG(4). Whether these antibody effects may serve as predictive biomarkers of clinical efficacy in individual patients requires further investigation.

Continuous apple consumption induces oral tolerance in birch‐pollen‐associated apple allergy

Patients with birch pollen allergy (major allergen: Bet v 1) have often an associated oral allergy syndrome (OAS) to apple, which contains the cross-reactive allergen Mal d 1. As successful birch pollen immunotherapy does not consistently improve apple related OAS symptoms, we evaluated whether regular apple consumption has an effect on OAS and immune parameters of Mal d 1 or Bet v 1 allergy. A total of 40 patients with a clear history of birch pollen rhinoconjunctivitis and associated OAS to apple were included in an open, randomized, controlled clinical trial: 27 patients consumed daily defined amount of apple (1-128 g), doubling the amount every two to three weeks, while 13 patients remained untreated. Primary endpoint was the proportion of patients that achieved tolerance to at least 128 g of apple at the end of the study after 8 months. Exploratory endpoints were questionnaire about cross-reactive food and pollen allergy symptoms, conjunctival provocation test with birch pollen and Bet v 1, and in vitro tests (tIgE, sIgE, and IgG4 to Mal d 1 and Bet v 1; basophil activation test with both allergens). Seventeen of 27 patients in active group and none of 13 patients in control group (P = 0.0001) could tolerate a whole apple after the intervention. However, differences in endpoints reflecting systemic immune reactivity did not reach statistical significance. In patients with OAS to apple, tolerance can be safely induced with slowly, gradually increasing consumption of apple. However, the observation of a relapse after discounting of apple consumption and absence of immunologic changes suggest that induced tolerance is only transient.

Increasing long-term safety of seasonal grass pollen sublingual immunotherapy: the ECRIT study

Objective: The usual build-up phase of days or weeks in allergen-specific immunotherapy entails inconveniences for individuals with symptoms only during the pollen season. Additionally, affected individuals often appear for treatment shortly before the expected start of the season without enough time for titration. This double-blind, placebo-controlled study evaluated the safety of ultra-rush grass pollen immunotherapy with sublingual drops (Staloral)® in co-seasonal treatment over three consecutive seasons.Methods: 209 patients with grass pollen allergic rhinitis received ultra-rush titration (30, 90, 150 and 300 index of reactivity (IR)) of a five grass pollen mixture or placebo every 20 min at the start of the season, followed by 300 IR daily or placebo until the end of the respective season for three consecutive years. Adverse events were documented.Results: Mean treatment duration varied between seasons (81.8 − 92.7 days). No systemic or anaphylactic reactions were reported and no unexpected adverse events were observed. Adverse events included application site irritation, oedema, abdominal pain and diarrhoea. Fourteen patients discontinued treatment due to adverse events (placebo: four (6%) patients, verum: ten (7%) patients). Adverse events decreased in frequency over each consecutive year of treatment.Conclusion: Seasonal sublingual immunotherapy with ultra-rush titration is well tolerated even when administered as co-seasonal treatment. It may be a valuable option for patients who present late.

Birch-Apple Syndrome Treated with Birch Pollen Immunotherapy

Background: The most common pollen-fruit cross-reaction is the birch-apple syndrome. Allergen immunotherapy (IT) is clearly effective for birch allergy, but its efficacy on apple allergy is controversial. We performed a randomized study on patients with birch-apple syndrome to evaluate the outcome of subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT). Methods: Forty patients underwent IT with a birch extract (Staloral; Stallergenes, Antony, France), 20 by SCIT and 20 by SLIT. After 1 year of treatment, 15 patients (8 for SCIT and 7 for SLIT) accepted to undergo an oral apple challenge. Measurements of specific IgE to Bet v 1 and Mal d 1 and related allergens Api g 1 and Dau c 1 were obtained in 10 patients, at baseline and after IT. Results: Two of 8 SCIT-treated patients (25%) and 1 of 7 SLIT-treated patients (14.2%) developed complete tolerance to apple. In the remaining patients, an increase in the provocative dose was found in 3 of the SCIT-treated (37.5%) and 2 of the SLIT-treated patients (28.6%). Changes in the levels of specific IgE to Mal d 1 were unrelated to clinical results. Conclusions: These findings suggest that different doses of birch extract may be needed in different patients to improve the associated apple allergy and that a finer diagnostic work-up in selecting patients with birch-apple syndrome who are candidates to respond to birch pollen IT also concerning apple allergy is required.

A national audit of pollen immunotherapy for children in the United Kingdom: patient selection and programme safety

Specific immunotherapy (SIT) is an effective treatment for grass and/or tree pollen-induced severe allergic rhinoconjunctivitis. However, there are limited detailed data on the use of immunotherapy in children in the United Kingdom. We audited NHS paediatric practice against current national guidelines to evaluate patient selection, SIT modalities and adverse events (AEs). Paediatricians offering pollen SIT were identified through the British Society of Allergy and Clinical Immunology Paediatric Allergy Group (BSACI-PAG) and the database of SIT providers compiled for the Royal College of Physicians and Royal College of Pathologists 2010 joint working group. Standardized proformas were returned by 12 of 20 centres (60%), including 12 of 14 centres offering subcutaneous immunotherapy (SCIT) (85%). Three hundred and twenty-three children, with mean age 11 years at initiation (69% boys), had undergone 528 SIT cycles (SCIT 31%) over 10 years. Fifty-five percent of all patients had asthma. Among SCIT programmes 24.5% patients had perennial (± seasonal) asthma; 75.6% of asthmatics undertaking SCIT had treatments at BTS/SIGN step 2 or above. AEs occurred frequently (50.4% of all SIT cycles) but were mild. In sublingual immunotherapy (SLIT) treatment, local intraoral immediate reactions were most common (44.9% SLIT cycles), as compared with delayed reactions around the injection site in SCIT (28.3% SCIT cycles). An asthma diagnosis had no impact on the number of cycles with AEs, or the severity reported. Few cycles (2.9%) were discontinued as a result of AE(s). Pollen SIT is available across England, though small numbers of children are being treated. Current national guidelines to exclude asthmatic children in SIT programmes are not being adhered to by most specialist paediatric allergy centres. SCIT and SLIT has been well tolerated. Review of patient selection criteria is needed and may allow greater use of this therapeutic option in appropriate clinical settings.

Oralair®: sublingual immunotherapy for the treatment of grass pollen allergic rhinoconjunctivitis

Oralair® is a sublingual grass pollen immunotherapy tablet that was authorized for use in Europe on 26 November 2009 and is currently in Phase III clinical trials in the USA. It is indicated for the management of grass pollen allergic rhinitis with or without conjunctivitis in adults, adolescents and children (above the age of 5) with clinically relevant symptoms, confirmed by a positive cutaneous test and/or a positive titer of the specific IgE to the grass pollen. Treatment is composed of an initiation phase (3-day dose escalation: 100 IR [index of reactivity] on day 1, 200 IR on day 2 and 300 IR on day 3) and a continuation phase at a dosage of 300 IR/day. Treatment is scheduled to start approximately 4 months before the actual start of the pollen season and should be continued throughout the season. The treatment should be prescribed and initiated by an experienced allergy specialist.

Fungal immunotherapy in patients with allergic fungal sinusitis

Allergic fungal sinusitis is a disease for which optimal treatment is unclear. Previous studies using fungal immunotherapy reported less recurrence after surgery. There has been concern that traditional high-dose immunotherapy could induce systemic hypersensitivity in patients with this condition. To determine the safety of high-dose subcutaneous fungal immunotherapy in patients with allergic fungal sinusitis. Safety of high-dose subcutaneous fungal immunotherapy was assessed in 14 patients from our clinic who met diagnostic criteria for allergic fungal sinusitis. Results were compared to a control group of 14 patients with chronic rhinosinusitis without allergic fungal sinusitis who received subcutaneous fungal immunotherapy. We also performed a literature search to identify all previous reports of subcutaneous fungal immunotherapy. No differences between numbers of immediate local or large local reactions, delayed local reactions, or required dose adjustments were noted between patient and control groups. One patient from each group experienced a mild systemic urticarial reaction to immunotherapy. Similarly, there were no differences in complications in either group that also received immunotherapy with nonfungal allergens. No patient developed evidence of immune complex disease. Eight publications were identified for inclusion in our literature analysis, 7 of which used low-dose subcutaneous immunotherapy. None of these noted complications more serious than local reactions. Our data demonstrate that subcutaneous fungal immunotherapy in patients with allergic fungal sinusitis is unlikely to cause adverse reactions other than those occurring with pollen immunotherapy. Clinical trials of high-dose, traditional immunotherapy with fungal allergens for efficacy may proceed in patients with allergic fungal sinusitis without undue concern.

Recombinant allergen-based monitoring of antibody responses during injection grass pollen immunotherapy and after 5 years of discontinuation

Subcutaneous injection immunotherapy (SCIT) is considered as antigen-specific and disease-modifying treatment with long-lasting effect. We used a panel of recombinant grass pollen allergens for analyzing allergen-specific IgE, IgG(1) -IgG(4) , IgM, IgA, and light-chain (kappa, lambda) responses in grass pollen-allergic patients who had received one course of injection immunotherapy (SCIT) with an aluminum hydroxide-adsorbed grass pollen extract or only anti-inflammatory treatment. Serum samples were analyzed before and after 5 months of treatment as well as after 5 years. After 5 months of SCIT but not of anti-inflammatory treatment, IgG(1) > IgG(4) > IgG(2) > IgA antibody responses using both kappa and lambda light chains specific for major grass pollen allergens (Phl p 1, Phl p 5, Phl p 6, Phl p 2) increased significantly, whereas specific IgM or IgG(3) levels were unaltered. Allergen-dependent basophil degranulation was only inhibited with SCIT sera containing therapy-induced allergen-specific IgG antibodies. Likewise, decreases in Phl p 1- and Phl p 5-specific IgE levels and significant (P<0.001) reduction in symptom and medication scores were found only in the SCIT group but not in the group of patients receiving anti-inflammatory treatment. After 5 years, allergen-specific IgG antibody levels in the SCIT group had returned to baseline levels and there was no significant difference regarding symptoms between the SCIT and non-SCIT groups. The results from our observational study demonstrate that only SCIT but not anti-inflammatory treatment induces allergen-specific IgG and reduces boosts of allergen-specific IgE production but that one SCIT course was not sufficient to achieve long-term immunological and clinical effects.

Medication persistence with long-term, specific grass pollen immunotherapy measured by prescription renewal rates

Objective:We assessed medication persistence using prescription renewal rates for grass pollen specific immunotherapy (SIT) in a representative population of patients in Germany to evaluate whether the perception of superior persistence for the subcutaneous route compared to the sublingual route could be confirmed in clinical practice.Methods:Individual prescriptions for allergen immunotherapy were extracted from a national prescription database (INSIGHT Health) and followed over 3 years on a per-patient basis. However, patients’ medical history and treatment schedules were not available for analysis. Products were identified by the national drug code (PZN number) and grouped to either subcutaneous immunotherapy (SCIT) with natural extract injections, SCIT with modified allergens (allergoids) or sublingual immunotherapy (SLIT) with natural pollen extract solutions. Persistence was defined as at least one prescription of the individual drug in the respective years.Results:A total of 1409 patients started SIT in 2005 (112, 695, and 602 for natural extract SLIT, natural extract SCIT, and allergoid SCIT, respectively). In 2006, 71%, 55%, and 59% of those patients had at least one renewal prescription of natural extract SLIT, natural extract SCIT, and allergoid SCIT, respectively, as well as 51%, 34%, and 39% in 2007. In both years, persistence with natural extract SLIT was significantly higher than with natural extract SCIT (p = 0.0015 for 2006, p = 0.0003 for 2007) and allergoid SCIT (p = 0.0152 for 2006, p = 0.0111 for 2007). There were no significant differences between the two SCIT groups.Conclusion:Medication persistence with grass pollen SIT in a representative sample of patients in Germany was similar to published medication persistence in asthma and COPD patients. The sublingual application route shows significantly better persistency than the subcutaneous route with native allergens or allergoids.

Effect of Grass Pollen Immunotherapy on Asthma Quality of Life

Effect of Grass Pollen Immunotherapy on Asthma Quality of Life

Long-term tolerance after allergen immunotherapy is accompanied by selective persistence of blocking antibodies

Grass pollen immunotherapy for allergic rhinitis is a disease-modifying treatment that results in long-term clinical tolerance lasting years after treatment discontinuation. Active treatment is associated with generation of inhibitory grass pollen-specific IgG antibodies capable of blocking allergen-IgE interactions. We sought to investigate the involvement of IgG-associated inhibitory antibodies with long-term clinical tolerance after discontinuation of grass pollen immunotherapy. We conducted a 4-year study in which patients who had moderate-to-severe allergic rhinitis underwent a randomized, double-blind, placebo-controlled discontinuation of subcutaneous grass pollen immunotherapy. All subjects received grass pollen immunotherapy injections for 2 years (n = 13), followed by a further 2 years of either active (n = 7) or placebo (n = 6) injections. Clinical outcomes included seasonal symptoms and use of rescue medication. Serum specimens were collected at baseline and after 2 and 4 years for quantification of allergen-specific IgG antibodies. Sera were also tested for IgG-dependent inhibitory bioactivity against IgE-allergen binding in cellular assays by using flow cytometry and confocal microscopy to detect binding of IgE-grass pollen allergen complexes to B cells. Clinical improvement was maintained after 2 years of discontinuation. Although immunotherapy-induced grass pollen-specific IgG1 and IgG4 levels decreased to near-preimmunotherapy levels during discontinuation, inhibitory bioactivity of allergen-specific IgG antibodies was maintained unchanged. Grass pollen immunotherapy induces a subpopulation of allergen-specific IgG antibodies with potent inhibitory activity against IgE that persists after treatment discontinuation and that could account for long-term clinical tolerance.

Local allergic rhinitis: Allergen tolerance and immunologic changes after preseasonal immunotherapy with grass pollen

Local allergic rhinitis: Allergen tolerance and immunologic changes after preseasonal immunotherapy with grass pollen