Grass Pollen Sublingual Immunotherapy Research Articles

Immunothérapie allergénique aux pollens de graminées : profil de sécurité et d’efficacité

IntroductionRespiratory allergies to grass pollens are very widespread in the general population and the treatment is generally symptomatic which sometimes remains insufficient. Grass pollen allergen immunotherapy is currently the only etiological treatment of seasonal allergic rhinitis apart from allergenic eviction. AimThe aim was to study the effectiveness of sublingual ITA tablets with 5-grasses on allergic disease and describe the adverse effects after one year of treatment. MethodsWe conducted a prospective, descriptive and evaluative study including 40 patients suffering from grass pollen allergic rhinitis. A grass pollen sublingual allergen immunotherapy was received and patients were followed during a one-year treatment to study the efficacy and the safety profile. ResultsThe mean age was 30.9±12.25 years. The sex ratio (M/F) was 0.48. Allergic conjunctivitis was associated in 70% and allergic asthma was associated in 48% of cases. Allergen immunotherapy side effects were mild, consisting of local side effects. No severe side effects were observed. A decrease in allergic rhinitis symptoms was observed in 83% with improvement in medication score in 65%. All patients noted a decrease in conjunctivitis symptoms with a total regression in 54% of cases. A better asthma control was noted in 33%. Among the 19 patients suffering from asthma, we could decrease the drug use in 63% of cases during the first year of treatment. An improvement of the quality of life was observed in 78% of cases. Allergen immunotherapy was significantly more efficient in allergic rhinitis and conjunctivitis with patients under 30years old. ConclusionGrass pollen allergen immunotherapy leads safely to the regression of allergy symptoms and improves the therapeutic load and the quality of life.

Plant Food Allergy Improvement after Grass Pollen Sublingual Immunotherapy: A Case Series.

Background: Cross-reactivity between pollens and plant food has been widely described. Pollen extract subcutaneous immunotherapy in patients with pollens and plant food allergy has been shown to improve tolerance not only to inhalant allergens but also to reduce symptoms in patients with various food allergies. Methods: We retrospectively report our experience with 15 female patients with a positive history for moderate, persistent allergic rhinitis due to grass pollen and oropharyngeal symptoms after ingestion of different plant food. These patients followed a five-grass pollen sublingual tablet immunotherapy for three years in a discontinuous pre-co-seasonal scheme. Results: All 15 patients treated with the 5-grass pollen sublingual tablet immunotherapy, taken once daily for 3 years on a 7-month course, showed improved ocular/nasal symptoms, with a reduction in the use of symptomatic drugs (e.g., nasal corticosteroids and H1 antihistamines). After the first seven-month course of immunotherapy, all patients declared a good tolerance to the intake of fruits and vegetables, and in particular, good tolerance to the offending foods. Conclusions: In conclusion, we have observed improvement of both respiratory and plant food allergies after sublingual immunotherapy (SLIT) with a five-grass pollen tablet.

Induction of IL-10-producing type 2 innate lymphoid cells by allergen immunotherapy is associated with clinical response

The role of innate immune cells in allergen immunotherapy that confers immune tolerance to the sensitizing allergen is unclear. Here, we report a role of interleukin-10-producing type 2 innate lymphoid cells (IL-10+ ILC2s) in modulating grass-pollen allergy. We demonstrate that KLRG1+ but not KLRG1- ILC2 produced IL-10 upon activation with IL-33 and retinoic acid. These cells attenuated Th responses and maintained epithelial cell integrity. IL-10+ KLRG1+ ILC2s were lower in patients with grass-pollen allergy when compared to healthy subjects. In a prospective, double-blind, placebo-controlled trial, we demonstrated that the competence of ILC2 to produce IL-10 was restored in patients who received grass-pollen sublingual immunotherapy. The underpinning mechanisms were associated with the modification of retinol metabolic pathway, cytokine-cytokine receptor interaction, and JAK-STAT signaling pathways in the ILCs. Altogether, our findings underscore the contribution of IL-10+ ILC2s in the disease-modifying effect by allergen immunotherapy.

Exploring novel systemic biomarker approaches in grass-pollen sublingual immunotherapy using omics.

BackgroundSublingual allergen‐specific immunotherapy (SLIT) intervention improves the control of grass pollen allergy by maintaining allergen tolerance after cessation. Despite its widespread use, little is known about systemic effects and kinetics associated to SLIT, as well as the influence of the patient sensitization phenotype (Mono‐ or Poly‐sensitized). In this quest, omics sciences could help to gain new insights to understand SLIT effects.Methods47 grass‐pollen‐allergic patients were enrolled in a double‐blind, placebo‐controlled, multicenter trial using GRAZAX® during 2 years. Immunological assays (sIgE, sIgG4, and ISAC) were carried out to 31 patients who finished the trial. Additionally, serum and PBMCs samples were analyzed by metabolomics and transcriptomics, respectively. Based on their sensitization level, 22 patients were allocated in Mono‐ or Poly‐sensitized groups, excluding patients allergic to epithelia. Individuals were compared based on their treatment (Active/Placebo) and sensitization level (Mono/Poly).ResultsKinetics of serological changes agreed with those previously described. At two years of SLIT, there are scarce systemic changes that could be associated to improvement in systemic inflammation. Poly‐sensitized patients presented a higher inflammation at inclusion, while Mono‐sensitized patients presented a reduced activity of mast cells and phagocytes as an effect of the treatment.ConclusionsThe most relevant systemic change detected after two years of SLIT was the desensitization of effector cells, which was only detected in Mono‐sensitized patients. This change may be related to the clinical improvement, as previously reported, and, together with the other results, may explain why clinical effect is lost if SLIT is discontinued at this point.

Nasal reactivity evaluation in children with allergic rhinitis receiving grass pollen sublingual immunotherapy.

Background: The European Academy of Allergy and Clinical Immunology guidelines, strongly recommended allergen immunotherapy (AIT) as an effective treatment to achieve long-term clinical benefits and to modify the natural history of allergic diseases. Sublingual immunotherapy (SLIT) offers the possibility of home administration, which improves patient comfort and compliance. Objective: The primary outcome of this study was to assess the change in nasal reactivity after grass-pollen AIT treatment. Methods: This was a monocentric, prospective, observational study conducted in Rome from September 2016 to June 2018, in the Pediatric Department of Policlinico Umberto I. We enrolled children, ages between 6 and 12 years, with persistent allergic rhinitis (AR), sensitized to grass pollen. At the first visit (V0, September 2016), one group received the first dose of oral immunotherapy for grass-pollen spray buccal and the other group continued only standard therapy. All the patients had nasal specific immunoglobulin I (IgE) assay (Phl p1, Phl p5), active anterior rhinomanometry with a nasal provocation test (NPT), and spirometry. The patients attended two follow-up visits, in May 2017 (V1) and May 2018 (V2), with the same examinations as at V0. Results: During the treatment, we observed, in the treated group, a significant increase in the mean nasal flow compared with untreated children (p < 0.001). In the AIT group, we found an improvement of nasal function and only 21.05% of all the children in the active group with a positive NPT result at V2. In the control group, we found, at V2, a worsening of nasal function, with 89.47% of the children with a positive NPT result. Furthermore, we found a significant reduction of nasal specific IgE levels at the end of the observation period in the treated group. Conclusion: Analysis of our data provided evidence for a clinical effect of SLIT in inducing clinical changes and allergen tolerance in children with AR.

Satisfaction with grass pollen sublingual immunotherapy assessed by ESPIA questionnaire – first results from Bulgaria

Satisfaction with grass pollen sublingual immunotherapy assessed by ESPIA questionnaire – first results from Bulgaria

Immunotherapy for Upper Airway Disease Generates IL-10-Producing KLRG1 &lt;sup&gt;+&lt;/sup&gt; ILC2s that are Associated with Clinical Benefit

SummaryIn this study, we addressed the role of IL-10-producing ILCs in controlling grass pollen allergy. IL-10+ ILCs are comprised in KLRG1+ILC2-lineage cells and absent on CRTH2+ ILC2 which lack KLRG1. We observed that ILC2s in healthy subjects and grass pollen allergic patients show differential gene expression profiles. A cross-sectional study demonstrates that IL-10-producing KLRG1+ ILC2s are strongly reduced in patients with grass pollen and house dust mite allergy when compared to healthy subjects and those who have received grass pollen subcutaneous immunotherapy treatment. In a prospective double-blind, placebo-controlled trial of grass pollen sublingual immunotherapy (SLIT), we observed that the capacity of ILC2 to produce IL-10 was restored in patients who received SLIT, but not patients receiving a placebo. Finally, we demonstrated that these IL-10-producing ILCs are functional and play a crucial role in restoring barrier function and tissue balance in allergic diseases.

A quality-of-life mapping function developed from a grass pollen sublingual immunotherapy trial to a tree pollen sublingual immunotherapy trial

Aims: Allergic rhinitis is caused by sensitivity to environmental allergens that can significantly impact quality-of-life. The objective of this analysis was to estimate health state utilities and quality-adjusted life days (QALDs) for a tree allergy immunotherapy trial, TT-04 (EudraCT No.2015-004821-15). Health-state utilities are a measure of patient preference for health states and are necessary to derive QALDs for cost-utility analysis. Preference-based utilities were not collected in the TT-04 trial, so a mapping algorithm was developed based on a similar grass allergy immunotherapy trial, GT-08 (EudraCT No. 2004-000083-27), to estimate utilities.Methods: A two-part model was developed to predict utilities for the GT-08 trial and applied to the TT-04 trial to estimate the difference in mean utility and QALDs between SQ tree sublingual immunotherapy (SLIT)-tablet and placebo.Results: Mean utility difference between SQ tree SLIT-tablet and placebo was 0.030 [95% CI = 0.015–0.046] during the birch pollen season (BPS), 0.019 [95% CI = 0.007–0.030] during the tree pollen season (TPS) and 0.018 [95% CI = 0.007–0.030] during the full trial. The treatment showed a QALD benefit of 1.26 [95% CI = 0.619–1.917] during the BPS, 1.90 [95% CI = 0.692–3.047] during the TPS, and 2.47 [95% CI = 0.930–4.101] during the full trial.Limitations: The generalizability of this algorithm is limited to allergy trials containing the same covariates as those present in the model. The analysis also assumes that grass and tree pollen allergy have the same relationship with EQ5D utilities, which is supported by the fact that both grass and tree pollen induce similar symptoms.Conclusions: Application of the mapping function enabled the calculation of QALDs associated with the treatment, with the caveat that data were extrapolated from grass seasonal allergy to tree seasonal allergy. The results showed a significant QALD benefit of the treatment over placebo in treatment of tree pollen-induced rhinoconjunctivitis.

Sublingual immunotherapy alters salivary IgA and systemic immune mediators in timothy allergic children.

Immunomodulatory effects of sublingual immunotherapy on systemic and mucosal mediators in allergic children are largely unexplored. The aim of this study was to investigate allergy-related cytokine and chemokine levels, as well as IgA-responses upon a 3-year treatment with timothy grass pollen sublingual immunotherapy in children with allergic rhinoconjunctivitis. From children included in the GRAZAX® Asthma Prevention study, blood and saliva samples were analyzed at inclusion, after 3years of treatment, and 2years after treatment ending. By means of Luminex and ELISA methodologies, allergy-related cytokines and chemokines were measured in plasma samples and allergen-stimulated peripheral blood mononuclear cell supernatants. Furthermore, studies of total, secretory, and Phl p 1-specific salivary IgA antibodies were performed using the same methods. GRAZAX® -treated children exhibited significantly higher levels of Phl p 1-specific salivary IgA and serum IgG4 , along with significantly lower skin prick test positivity, after 3years of treatment and 2years after treatment cessation. Additionally, plasma levels of the Th1-associated chemokines CXCL10 and CXCL11 were significantly higher in treated than untreated children at these time points. Timothy-induced ratios of IL-5/IL-13 over IFN-γ were significantly decreased after 3years with active treatment, as were symptoms of allergic rhinitis in terms of both severity and visual analogue scale scores. However, no consistent correlations were found between the clinical outcomes and immunologic parameters. Phleum pratense sublingual immunotherapy in grass pollen allergic children modulates the immune response in the oral mucosa as well as systemically-by increasing Th1-responses, decreasing Th2-responses, and inducing immunoregulatory responses-all signs of tolerance induction.

Lack of effect of Timothy grass pollen sublingual immunotherapy tablet on birch pollen–induced allergic rhinoconjunctivitis in an environmental exposure unit

BackgroundTimothy grass pollen allergen extract tablets (Grastek) are standardized sublingual immunotherapy tablets (SLIT-T) approved for the treatment of grass pollen–induced allergic rhinitis (AR) and conjunctivitis. Many grass allergic patients are also cosensitized to birch pollen. Whether Timothy grass SLIT-T can confer symptomatic benefits for birch pollen–induced AR symptoms is unknown. ObjectiveTo evaluate the treatment effect of Timothy grass SLIT-T for birch pollen–induced AR in participants sensitized to both grass and birch pollen using an environmental exposure unit (EEU). MethodsThis study was a phase 4, randomized, double-blind, placebo-controlled, parallel-group study that enrolled participants aged 18 to 65 years allergic to both timothy grass and birch pollen. After a baseline EEU birch pollen challenge, in which a minimum total nasal symptom score (TNSS) of 6 of 12 was required for enrollment, participants were randomized to receive Timothy grass SLIT-T or placebo taken once daily for 4 months. No confirmatory grass pollen challenge was performed. The primary end point was the change in TNSS averaged from assessments from hours 2 to 5 during the posttreatment birch pollen challenge compared with baseline. The secondary and exploratory end points included temporally identical changes in total ocular symptom score (TOSS), total rhinoconjunctivitis symptom score (TRSS), and individual symptom scores. ResultsThe difference in TNSS reduction after 4 months of therapy between the Timothy grass SLIT-T and placebo group was not significant (P = .83). Reductions in TOSS (P = .19) and TRSS (P = .67) were also comparable between groups. Findings between groups for individual symptom scores were similar (all P > .40), except for watery eyes, in which symptom reduction was slightly better in the placebo arm (P = .01). Timothy grass SLIT-T was well tolerated, and no serious adverse effects occurred. ConclusionA bystander effect of grass SLIT-T on birch pollen–induced AR symptoms was not detected. Symptomatic benefits of grass SLIT-T are likely allergen specific. Trial RegistrationClinicalTrials.gov identifier: NCT02394600.

Grass pollen sublingual immunotherapy tablets provide long-term relief of grass pollen-associated allergic rhinitis and reduce the risk of asthma: findings from a retrospective, real-world database subanalysis

ABSTRACTBackground: We assessed real-world, long-term effectiveness of two marketed sublingual immunotherapy (SLIT) tablets for allergic rhinitis (AR), and their impact on allergic asthma (AA) onset/progression.Methods: Retrospective, longitudinal German prescription database subanalysis of AR patients receiving 5- or 1-grass pollen SLIT tablets (n = 1,466/1,385), versus patients not using allergy immunotherapy (AIT) (n = 71,275).Primary endpoint: change over time in AR symptomatic medication prescriptions after treatment cessation; secondary endpoints: new asthma onset, and change over time in asthma medication prescriptions during treatment/follow-up periods.Results: Mean number of AR medication prescriptions was significantly decreased during follow-up (of up to 6 years) with both SLIT tablets versus the non-AIT group (p < 0.001).Over the full-analysis period, proportions of patients with new-onset asthma were 8.8% (odds ratio: 0.676, p = 0.011), 10.3% (odds ratio: 0.720, p = 0.060) and 11.6% in the 5- and 1-grass pollen SLIT tablet and non-AIT groups, respectively.For all treatment-analysis periods, both SLIT tablet groups were associated with fewer asthma medication prescriptions versus non-AIT controls.Conclusions: These findings confirm the real-world benefits of 5- and 1-grass-pollen SLIT tablets in slower AR progression, reduced risk of new asthma onset in the non-asthmatic population, and slower asthma progression in the asthmatic population.

Long-Term Impact of Grass-Pollen (GP) Sublingual Immunotherapy Tablet (SLIT) on Allergic Rhinitis (AR) and on Allergic Asthma (AA) Onset and Progression

Long-Term Impact of Grass-Pollen (GP) Sublingual Immunotherapy Tablet (SLIT) on Allergic Rhinitis (AR) and on Allergic Asthma (AA) Onset and Progression

Sublingual immunotherapy provides long-term relief in allergic rhinitis and reduces the risk of asthma: A retrospective, real-world database analysis.

BackgroundAllergy immunotherapy (AIT) is the only treatment for allergic rhinitis (AR) and/or allergic asthma (AA) with long‐term efficacy. However, there are few real‐life data on the progression of AR and/or AA in patients receiving AIT.ObjectivesTo assess the real‐world, long‐term efficacy of grass pollen sublingual immunotherapy (SLIT) tablets in AR and their impact on asthma onset and progression.MethodsIn a retrospective analysis of a German longitudinal prescription database, AR patients treated with grass pollen SLIT tablets were compared with a control group not having received AIT. Multiple regression analysis was used to compare changes over time in rescue symptomatic AR medication use after treatment cessation, asthma medication use, and the time to asthma onset in the two groups.ResultsAfter applying all selection criteria, 2851 SLIT and 71 275 control patients were selected for the study. After treatment cessation, AR medication use was 18.8 percentage points lower (after adjustment for covariates, and relative to the pretreatment period) in SLIT tablet group than in the non‐AIT group (P<.001). Asthma onset was less frequent in SLIT tablet group than in non‐AIT group (odds ratio: 0.696, P=.002), and time to asthma was significantly longer (hazard ratio: 0.523; P=.003). After SLIT cessation, asthma medication use fell by an additional 16.7 percentage points (relative to the pretreatment period) in the SLIT tablet group vs the non‐AIT group (P=.004).ConclusionsReal‐world treatment of AR patients with grass pollen SLIT tablets was associated with slower AR progression, less frequent asthma onset, and slower asthma progression.

Systemic reaction to timothy grass pollen sublingual immunotherapy

Systemic reaction to timothy grass pollen sublingual immunotherapy

Effect of 2 Years of Treatment With Sublingual Grass Pollen Immunotherapy on Nasal Response to Allergen Challenge at 3 Years Among Patients With Moderate to Severe Seasonal Allergic Rhinitis

Sublingual immunotherapy and subcutaneous immunotherapy are effective in seasonal allergic rhinitis. Three years of continuous treatment with subcutaneous immunotherapy and sublingual immunotherapy has been shown to improve symptoms for at least 2 years following discontinuation of treatment. To assess whether 2 years of treatment with grass pollen sublingual immunotherapy, compared with placebo, provides improved nasal response to allergen challenge at 3-year follow-up. A randomized double-blind, placebo-controlled, 3-parallel-group study performed in a single academic center, Imperial College London, of adult patients with moderate to severe seasonal allergic rhinitis (interfering with usual daily activities or sleep). First enrollment was March 2011, last follow-up was February 2015. Thirty-six participants received 2 years of sublingual immunotherapy (daily tablets containing 15 µg of major allergen Phleum p 5 and monthly placebo injections), 36 received subcutaneous immunotherapy (monthly injections containing 20 µg of Phleum p 5 and daily placebo tablets) and 34 received matched double-placebo. Nasal allergen challenge was performed before treatment, at 1 and 2 years of treatment, and at 3 years (1 year after treatment discontinuation). Total nasal symptom scores (TNSS; range; 0 [best] to 12 [worst]) were recorded between 0 and 10 hours after challenge. The minimum clinically important difference for change in TNSS within an individual is 1.08. The primary outcome was TNSS comparing sublingual immunotherapy vs placebo at year 3. Subcutaneous immunotherapy was included as a positive control. The study was not powered to compare sublingual immunotherapy with subcutaneous immunotherapy. Among 106 randomized participants (mean age, 33.5 years; 34 women [32.1%]), 92 completed the study at 3 years. In the intent-to-treat population, mean TNSS score for the sublingual immunotherapy group was 6.36 (95% CI, 5.76 to 6.96) at pretreatment and 4.73 (95% CI, 3.97 to 5.48) at 3 years, and for the placebo group, the score was 6.06 (95% CI, 5.23 to 6.88) at pretreatment and 4.81 (95% CI, 3.97 to 5.65) at 3 years. The between-group difference (adjusted for baseline) was -0.18 (95% CI, -1.25 to 0.90; [P = .75]). Among patients with moderate to severe seasonal allergic rhinitis, 2 years of sublingual grass pollen immunotherapy was not significantly different from placebo in improving the nasal response to allergen challenge at 3-year follow-up. clinicaltrials.gov Identifier: NCT01335139; EudraCT Number: 2010-023536-16.

Basophil expression of diamine oxidase: A novel biomarker of allergen immunotherapy response

Immunotherapy inhibits basophil histamine release, but the assay is cumbersome, and no one has studied the effects of immunotherapy withdrawal. Intracellular fluorochrome-labeled diamine oxidase (DAO) was used as a novel functional readout of basophil histamine release after immunotherapy. Results were compared with conventional basophil surface expression of activation markers. Subcutaneous immunotherapy (SCIT)-treated patients (n= 14), sublingual immunotherapy (SLIT)-treated patients (n= 12), participants who completed 3 years of treatment with grass pollen sublingual immunotherapy (the SLIT-TOL group; n= 6), patients with untreated seasonal allergic rhinitis (SAR; n= 24), and nonatopic control subjects (n= 12) were studied. Intracellularly labeled DAO(+) and surface expression of CD203c(bright), CD63(+), and CD107a(+) on chemoattractant receptor-homologous molecule expressed on TH2 lymphocytes (CRTh2)-positive basophils were measured by means of flow cytometry. Serum IgG4 levels and serum inhibitory activity for IgE-allergen complex binding to B cells (IgE-FAB) and basophil histamine release were also determined. Proportions of allergen-stimulated DAO(+)CRTh2(+) basophils were higher in participants in the SCIT, SLIT, and SLIT-TOL groups (all P< .0001) compared with those in patients in the SAR group. Similarly, there were lower proportions of CRTh2(+) basophils expressing surface CD203c(bright) (all P< .001), CD63 (all P< .001), and CD107a (allP< .01). Rhinitis symptoms were lower in the SCIT, SLIT, and SLIT-TOL groups (P< .001) compared with those in the SAR group. Serum inhibitory activity for IgE-FAB and basophil histamine release were also significantly greater in all immunotherapy groups (P< .05) compared with the SAR group. These results support long-term clinical and immunologic tolerance during and after grass pollen immunotherapy. Intracellularly labeled DAO expression by basophils merits further investigation as a surrogate biomarker for monitoring efficacy and tolerance after immunotherapy.

Objective approach for fending off the sublingual immunotherapy placebo effect in subjects with pollenosis: double-blinded, placebo-controlled trial

BackgroundSymptom scoring for the assessment of allergen immunotherapy is associated with a substantial placebo effect. ObjectiveTo assess the ability of exhaled breath temperature (EBT), a putative marker of airway inflammation, to evaluate objectively the efficacy of grass pollen sublingual immunotherapy in a proof-of-concept study. MethodsThis was a double-blinded, placebo-controlled clinical trial in 56 subjects (mean ± SD 30 ± 12 years old, 33 men) sensitized to grass pollen. The objective measurements were EBT, spirometry, and periostin and high-sensitivity C-reactive protein in blood. Overall discomfort scored on a visual analog scale was used as a proxy for subjective symptoms. Evaluations were performed before, during, and after the grass pollen season. ResultsFifty-one subjects (25 and 26 in the active treatment and placebo groups, respectively) were assessed before and during the pollen season. The mean pre- vs in-season increase in EBT was significantly smaller (by 59.1%) in the active treatment than in the placebo group (P = .030). Of the other objective markers, only the blood periostin level increased significantly during the pollen season (P = .047), but without intergroup differences. Subjectively, the mean pre- vs in-season increase in the visual analog scale score was 32.3% smaller in the active treatment than in the placebo group, although this difference did not reach statistical significance (P = .116). ConclusionThese results suggest that the efficacy of grass pollen sublingual immunotherapy can be assessed by EBT, a putative quantitative measurement of airway inflammation, which is superior in its power to discriminate between active and placebo treatment than a subjective assessment of symptoms assessed on a visual analog scale. Trial Registrationclinicaltrials.gov Identifier: NCT01785394.

IL-35-Producing T Cells (iTR35) Inhibit Th2 Effector Function, Induce Infectious Tolerance and Are Elevated Following Grass Pollen Sublingual Immunotherapy

IL-35-Producing T Cells (iTR35) Inhibit Th2 Effector Function, Induce Infectious Tolerance and Are Elevated Following Grass Pollen Sublingual Immunotherapy

Heterogeneity of antibody responses among clinical responders during grass pollen sublingual immunotherapy

During allergen-specific sublingual immunotherapy (SLIT), the relevance of changes in specific IgE and IgG antibody titres to treatment efficacy remains to be evaluated at an individual patient level. To investigate whether antibody responses can be used as biomarkers for SLIT efficacy. Comprehensive quantitative, qualitative and functional analyses of allergen-specific IgA, IgE, IgG1-4 and IgM responses were performed using purified Phl p 1 to 12 allergens in sera, saliva and nasal secretions from 82 grass pollen allergic patients. These patients were enrolled in a randomized, double-blind placebo-controlled study and assessed in an allergen challenge chamber (ClinicalTrials.gov NCT00619827). Antibody responses were monitored in parallel to clinical responses before and after daily sublingual treatment for 4months with either a grass pollen or a placebo tablet. A significant mean improvement (i.e. 33-40.6%) in rhinoconjunctivitis total symptom scores was observed in SLIT recipients, irrespective of their baseline patterns of IgE sensitization (i.e. narrow, intermediate, broad) to grass pollen allergens. SLIT did not induce any de novo IgE sensitization. Clinical responders encompassed both immunoreactive patients who exhibited strong increases in titres, affinity and/or blocking activity of grass-pollen-specific IgGs (representing 17% of treated patients), as well as patients with no detectable antibody responses distinguishing them from the placebo group. No significant changes were detected in antibody titres in saliva and nasal washes, even in clinical responders. Sublingual immunotherapy with a grass pollen tablet is efficacious irrespective of the patients' baseline sensitization to either single or multiple grass pollen allergens. Seric IgG responses may contribute to SLIT-induced clinical tolerance in a fraction (i.e. 17%) of patients, but additional immune mechanisms are involved in most patients. Consequently, antibody responses cannot be used as a marker of SLIT efficacy at an individual patient level.

Grading local side effects of sublingual immunotherapy for respiratory allergy: Speaking the same language

Sublingual immunotherapy (SLIT) is increasingly used worldwide. Despite its safety being well ascertained, there is no universally accepted system to grade and classify its adverse events (AEs). According to the literature, it seems reasonable to classify and grade systemic side effects by using the previously published World Allergy Organization recommendations. On the other hand, local side effects are the most frequent with SLIT, sometimes leading to its discontinuation. Therefore grading of the severity of local side effects was perceived as necessary for the purpose of uniform reporting, classification, and quantification of this aspect. AWorld Allergy Organization Taskforce, after examining the available literature and the postmarketing surveillance data, proposed a clinically based grading of the severity of local AEs caused by SLIT. The use of the Medical Dictionary for Regulatory Activities nomenclature for AEs was also included in this context. The proposed grading system for SLIT-induced local reactions is expected to improve and harmonize surveillance and reporting of the safety of SLIT.