Explore the vast range of titles available.

To evaluate tolerability of subcutaneous immunotherapy, in a polymerized mixture ( / ) depot presentation.  A total of 47 poly-allergic patients received: an abbreviated schedule with three injections at weekly intervals or a cluster schedule with two administrations in 1 day. Both treatments continued with 3 monthly maintenance administrations. Two systemic reactions, (4.3%). One grade 0 and one grade I. No local reactions. Immunoglobulin levels, increased significantly at final visit versus baseline in sIgG and sIgG4; in both schedules and allergens, no significant changes in specific immunoglobulin E levels were detected. Cutaneous reactivity at final visit decreased significantly. Both administration schedules with polymerized mixture of / , presented an excellent tolerability profile and induced preliminary efficacy changes.

Background: An aluminum hydroxide-adsorbed depot allergoid preparation of six-grass pollen allergens has been developed for short-term preseasonal immunotherapy in pollinosis. However, only limited knowledge exists about its immunological and clinical effects. The aim of this study was to evaluate the basophil response, which can explain early clinical findings of short-term preseasonal allergoid immunotherapy in allergic rhinitis. Methods: In a double-blind, placebo-controlled study, 31 patients allergic to grass pollens received one course of short-term preseasonal allergoid immunotherapy or placebo. Immunogenicity was assessed by the levels of specific IgG4, IgE antibodies and an allergen-induced CD203c basophil activation test. The primary clinical end point was the combined symptom and medication score/average combined score (ACS). Results: There was a 52.9% difference in ACS between the treatment and placebo groups in favor of immunotherapy (p = 0.01). Active treatment induced Phleum pratense-specific IgG4 and IgE antibodies (p < 0.05). A decrease in allergen-induced basophil activation at submaximal allergen concentrations was demonstrated at the end of immunotherapy and at the peak of the grass pollen season after immunotherapy. Conclusions: This study shows that grass pollen-allergic patients treated with one course of short-term preseasonal allergoid immunotherapy exhibit a decrease in allergen-induced basophil activation, an increase in allergen-specific IgG4 antibodies and early clinical improvement.

Background: One hundred years ago, Noon [Lancet 1911;1:1572–1573], using conjunctival provocation testing (CPT), was the first to demonstrate the effectiveness of subcutaneous immunotherapy (SCIT) in grass-allergic subjects with hay fever. In this centenary year, we present data that, by use of CPT and allergen-specific IgG, replicate this observation and additionally confirm the allergen specificity of SCIT by using a double-blind design employing either grass or mite SCIT in dual grass- and mite-allergic individuals. Methods: Twenty adults (11 females) with perennial rhinoconjunctivitis and exacerbation of symptoms during the grass pollen season and in the autumn had immediate skin and conjunctival sensitivity and raised specific IgE to both Dermatophagoides farinae and Phleum pratense. Participants were randomly assigned to either timothy or D. farinae immunotherapy for 3 years. CPT and specific IgG tests to both allergens were performed annually. After 3 years, subjects gave their blinded overall evaluation. Results: Six mild-to-moderate general reactions occurred in 2 timothy- and 4 mite-treated patients. Four of these patients and 2 other patients withdrew from the study. Seven patients in each group completed the study. After 3 years of immunotherapy, the timothy CPT threshold concentration had increased 16- fold in timothy-treated patients (p < 0.05; between-group change, p < 0.05). The increase in the mite CPT threshold in mite- compared to grass-treated patients was 31-fold (p < 0.05). The overall assessment of conjunctival sensitivity was highly significant in favour of treatment (p < 0.015), as was that of allergen-specific IgG (p < 0.0001). Conclusions: Allergen immunotherapy is allergen species-specific, as judged by decreased conjunctival sensitivity and changes in allergen-specific IgG concentrations.

The effect of sublingual immunotherapy on quality of life (QoL) was examined in patients with grass pollen-induced rhinoconjunctivitis. Patients (n = 855) were randomised to once-daily grass allergen tablets (2,500; 25,000; or 75,000 SQ-T Phleum pratense extract; GRAZAX® ) or placebo. Treatment was initiated 8 weeks before the start of the grass pollen season and continued throughout. If symptoms were present, patients received loratadine or placebo rescue medication. There were three major findings: in patients using loratadine, grass allergen tablets provided QOL benefits over placebo; Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) score was 17% (p = 0.006) and 20% (p = 0.020) greater with 75,000 SQ-T tablet than with placebo at first and second seasonal visit, respectively; in patients not using loratadine, grass allergen tablets improved QoL more than placebo; RQLQ score was 21% greater (p = 0.021) with 75,000 SQ- T tablet at second seasonal visit; grass tablets (without loratadine) had a greater effect on QoL than loratadine alone. RQLQ score was 26% ( p = 0.014) greater with 75,000 SQ-T tablets than loratadine at second seasonal visit. These data show that sublingual immunotherapy with grass allergen tablets improves QOL in allergic rhinoconjunctivitis, reduces symptoms, and that this effect is greater than rescue antihistamine alone.

To establish the optimal dose of subcutaneous immunotherapy (SCIT) in patients with allergic rhinoconjunctivitis with/without asthma. One hundred and fifty-one patients were randomized to receive SCIT 0.25, 0.5, 1.0, 2.0 or 4.0 skin-prick test units ( or placebo. The primary end point was the variation in the concentration of extract needed to produce a positive nasal provocation test from baseline (V0) to final visit (FV). After 17 weeks, a dose-dependent trend was apparent in the concentration of extract needed to produce a positive nasal provocation response. Systemic adverse reactions occurred with 3.2% of administered doses. Grade III (n = 2) and IV (n = 2) events were observed only at the two highest doses. : depot SCIT showed signs of clinical and immunological efficacy by dose-dependently decreasing the allergen sensitization rate. Risk-benefit favored doses below 1.0 units for confirmatory trials.

A double-blind placebo-controlled study was conducted according to EMA guidelines, to evaluate safety, tolerability and short-term treatment effects of three up-dosing regimens of subcutaneous immunotherapy. Forty-two patients were randomized to groups: A (6 weekly doses), B (8 weekly doses) or C (eight doses, two clustered increasing doses over 3 weeks). The most frequent adverse events were local reactions. No serious adverse events were found. Higher number and more severe systemic reactions were reported in group C. A decrease in cutaneous responses and an increase of specific antibodies was shown in all active groups even at very short-term. subcutaneous immunotherapy in depot presentation exhibited good safety and tolerability. Group A seemed to show the best profile.

Grass pollen triggers nearly 30% of bronchial allergic asthma cases. While most Q8 research focuses on pollen allergens, pollen lipids may also influence allergic reactions. Previous studies demonstrated that Timothy grass (TG, Phleum pratense) lipids, such as phytoprostanes, can activate immune cells, promoting pro-allergic responses. However, the role of water-insoluble pollen glycolipids in allergic airway inflammation remains unclear. Thus, this study aimed to isolate and characterize glycolipids from TG pollen and evaluate their bioactivity in allergic airway inflammation. Lipids were extracted from the water-insoluble pollen fraction, separated by silica gel, and fractionated by HPLC. GC-MS, HR ESI-MS, and NMR confirmed the presence of di-galactosyldiacylglycerol (DGDG). The biological activity of fractions containing DGDG (DGDG-3 and DGDG-4) and synthetic DGDG variants was tested in vitro in murine and human cell systems and in vivo in mice. Fraction 4 induced strong proliferation of murine NKT cells and upregulated CD69 expression in human NKT cells. Synthetic DGDG variants (DGDG-1, DGDG-2, and DGDG-3) with defined acylation profiles stimulated robust NKT-cell proliferation, with DGDG-2 and DGDG-3 increasing IL-13 production, one of the key Th2 cytokines. In vivo, only these variants caused lung inflammation marked by eosinophil infiltration but did not increase airway resistance. This study reveals for the first time the structure-dependent role of DGDG of TG pollen grains in immune cell recognition in the context of allergic inflammation. Our data may pave the way for therapies targeting lipid components in combination with protein allergens.

Grass pollen allergies significantly contribute to atopic diseases such as asthma and allergic rhinitis, resulting in considerable healthcare burdens. Objective: In this study, molecular sensitization patterns to grass pollen in Swiss patients were addressed. The research utilized a retrospective cohort approach using ImmunoCAP™ ISAC testing from October 2015 to July 2020. Clinical histories, demographics, and skin prick test results were collected for analysis. The minimum patient age was 18 years and the average patient age was 41.3 years, with a female predominance (68.5%). In total, 4814 measurements were analyzed. Allergic rhinitis was the most common clinical symptom, followed by asthma and urticaria. A total of 1963 patients (40.8%) revealed sensitization to grass pollen. The most common sensitizations were found to the major allergens Phl p 1 (86%) and Phl p 5 (65%), but also to Phl p 4 (62%). Monosensitization was mostly found to allergens Phl p 1 (266/13.5%) and Phl p 4 (157/7.9%), and less so to Phl p 5 (33/1.7%). Notably, the Phl p 4-monosensitized subgroup showed only an 18% positivity rate in skin prick tests and presented mostly with urticaria. This study gives insights into the spectrum of grass pollen allergies in a Central European setting and underscores the possibly underestimated role of Phl p 4 among grass pollen allergens, especially in a subgroup that suffers mainly from seasonal urticaria. Monovalent sensitization to Phl p 4 can also cause seasonal rhinitis and might therefore be missed if only Phl p 1/p 5 are tested. A better understanding of sensitization patterns will further improve diagnosis and treatment options.

Purpose The trace element zinc is essential for immune function and its regulation. Since zinc deficiency and allergic hyperresponsive reactions are often accompanied, the influence of zinc on allergen-induced cell growth, CD4+ regulatory T (Treg) cell numbers and cytokine expression during allergic immune reactions was investigated. Methods Peripheral blood mononuclear cells (PBMCs) from non-atopic and atopic subjects were treated with timothy grass allergen pre-incubated with or without zinc. Proliferation was determined by analyzing the incorporation of 3 H-thymidine. Intracellular zinc and Foxp3 levels and cell surface antigens were measured by FACS, cytokine expression by ELISA and real-time PCR. Results Incubation with 50 μM zinc sulfate (Zn50) enhances cytosolic zinc concentrations in CD3+ T cells. The data also reveal that the combination of Zn50 plus allergen significantly reduces PBMC proliferation of atopic subjects. Additionally, Zn50 plus allergen enhances Th1 cytokine responses shown by increased interferon (IFN)-γ/interleukin (IL)-10 ratios as well as enhanced tumor necrosis factor-α release. In response to allergen, zinc increases Treg cells and upregulates the mRNA expression of cytotoxic T-lymphocyte antigen-4 in atopic subjects. Interestingly, Zn50 alone leads to an increase of CD4+CD25high(hi)+ cells in atopic and non-atopic subjects. Conclusions Zinc may regulate unwanted hyperresponsive immune reactions by suppressing proliferation through a significant shift from IL-10 to the Th1 cytokine IFN-γ, and enhanced regulatory T cell numbers. Therefore, zinc supplementation may be a promising tool for the therapy of allergies, without negatively affecting the immune system.

T cells play an important role in the pathogenesis of allergic diseases. However, the proteins considered as potential immunogens of allergenic T-cell responses have traditionally been limited to those that induce IgE responses. Timothy grass (TG) pollen is a well-studied inhaled allergen for which major IgE-reactive allergens have also been shown to trigger T helper 2 (Th2) responses. Here we examined whether other TG pollen proteins are recognized by Th2 responses independently of IgE reactivity. A TG pollen extract was analyzed by 2D gel electrophoresis and IgE/IgG immunoblots using pooled sera from allergic donors. Mass spectrometry of selected protein spots in combination with de novo sequencing of the whole TG pollen transcriptome identified 93 previously undescribed proteins for further study, 64 of which were not targeted by IgE. Predicted MHC binding peptides from the previoulsy undescribed TG proteins were screened for T-cell reactivity in peripheral blood mononuclear cells from allergic donors. Strong IL-5 production was detected in response to peptides from several of the previously undescribed proteins, most of which were not targeted by IgE. Responses against the dominant undescribed epitopes were associated with the memory T-cell subset and could even be detected directly ex vivo after Th2 cell enrichment. These findings demonstrate that a combined unbiased transcriptomic, proteomic, and immunomic approach identifies a greatly broadened repertoire of protein antigens targeted by T cells involved in allergy pathogenesis. The discovery of proteins that induce Th2 cells but are not IgE reactive may allow the development of safer immunotherapeutic strategies.