Subcutaneous immunotherapy has emerged as an effective option for treating allergic diseases. Here, we assessed the clinical impact of the mannan-conjugated birch pollen polymerized allergoid T502 in birch pollen-induced allergic rhinoconjunctivitis.

In this prospective, randomized, double-blind placebo-controlled phase III trial, 298 birch pollen-allergic adult patients were treated across 28 trial sites in Germany. Patients received either placebo or 23,000 mTU T502 subcutaneously over five pre-seasonal visits. Efficacy was assessed by comparing the combined symptom and medication score (CSMS) between placebo and T502 during the peak birch pollen season 2022. Safety, tolerability and immunologic effects were also analyzed.

During the peak birch pollen season, the median CSMS of the T502 group was reduced by 33% (p = 0.002) compared to placebo. The median daily symptom score and daily medication score were reduced by 30.4% (p < 0.001) and 56.3% (p = 0.045), respectively. Health related quality of life improved as reflected by reduction of RQLQ values by 31.5% (p < 0.0001). Production of Bet v 1 sIgG4 and Bet v 1 sIgG increased up to 6.2-fold and 3-fold respectively in the T502 group (p < 0.0001). The sIgE/sIgG4 ratio was strongly reduced in the T502 group at V7 (-62.9%, p < 0.0001). No fatalities nor serious adverse events were reported. In total, 16 systemic allergic reactions occurred (Grade I/II).

Treatment with T502 significantly reduced symptoms and medication need in rhinoconjunctivitis patients. The treatment is well tolerated and safe.

Regulatory T (Treg) cells are pivotal in immune tolerance to allergens. Low-dose IL-2 (IL-2LD) activates Treg cells.

Our aim was to assess IL-2LD efficacy for controlling clinical responses to allergen exposures.

RHINIL-2 was a phase-2a, randomized, double blind, placebo-controlled trial. Patients with allergic rhinitis to birch pollen (BP) were included; 66% of them had concomitant asthma. All had a total nasal symptom score (TNSS) of 5 or more following nasal exposure to BP in an environmental exposure chamber. Patients received 1 MUI per day of IL-2 (n = 12) or placebo (n = 12) for 5 days, followed by weekly injections for 4 weeks. Clinical responses to subsequent BP exposures in the environmental exposure chamber were evaluated by using TNSS, the rhinitis visual analog scale (VAS), and spirometry. The primary efficacy end point was the difference in TNSS area under the curve (AUC) between inclusion and day 40.

IL-2LD treatment induced a significant expansion of Treg cells. The difference in TNSS AUC between inclusion and day 40 AUC in the IL-2 and placebo groups was not significant. TNSS and visual analog scale AUCs were significantly reduced from baseline to day 40 in the IL-2LD group only (P = .04 and P = .01, respectively). The ratio of FEV1 to forced vital capacity (FEV1P) and the forced midexpiratory flow (FEF25%-75%) showed improvement in the IL-2LD-treated versus in the groups given placebo at day 40 (P = .04 and P = .04, respectively). However, the short treatment duration used in this study could not have effects on specific IgE or IgG4 levels given their half-life. There were no severe treatment-related adverse events.

IL-2LD is well tolerated in patients with allergy, even in those with asthma, thus clearing the path for further therapeutic development. Our work suggests that Treg cells can safely attenuate an ongoing allergic response. It paves the way for larger studies with longer treatment periods, which are needed to properly evaluate the therapeutic potential of IL-2 in allergy.

Allergic rhinitis and/or conjunctivitis (AR/C) induced by tree pollen is common and negatively impacts quality of life in children and adolescents. This phase III trial investigated the efficacy and safety of the SQ tree SLIT-tablet in a paediatric population (5-17 years) with moderate-to-severe AR/C induced by pollen from birch and trees in the birch homologous group.

Nine hundred and fifty-two subjects were randomized (1:1) to daily treatment with SQ tree SLIT tablet or placebo for up to 52 weeks and had free access to AR/C symptom-relieving medications. The primary endpoint was the average total combined score (TCS); sum of average daily symptom score (DSS) and average daily medication score (DMS) during the birch pollen season (BPS). Key secondary endpoints included average DSS and DMS during BPS and average TCS, DSS and DMS during tree pollen season (TPS).

SQ tree SLIT-tablet demonstrated a statistically significant and clinically relevant treatment effect compared with placebo for the TCS during BPS with an absolute treatment difference of 1.29 (95% CI: 0.58, 2.00; p = .0004) and a relative reduction of 21.9% (95% CI: 10.6, 31.9). Results were substantiated by reductions in both DSS and DMS versus placebo during the BPS and in DSS, DMS and TCS during the TPS. Treatment was generally well tolerated. Most treatment-related adverse events were mild or moderate local administration site reactions.

This is the first paediatric trial to provide robust evidence of efficacy and safety of the SQ tree SLIT-tablet in tree polleninduced AR/C in a paediatric population (5-17 years).

In the realm of allergen immunotherapy (AIT), the quality of evidence varies across different products, making it unjustifiable to extend overall conclusions to all AIT products, as highlighted by WAO and EAACI.

To confirm the efficacy of the 300 IR 5-grass pollen sublingual AIT (SLIT)-tablet through a specific meta analysis of randomized controlled trials (RCTs) involving patients with allergic rhino conjunctivitis (ARC) with/without mild/intermittent asthma.

Data from published RCTs on the 300 IR 5-grass SLIT-tablet were gathered from electronic databases (MEDLINE, ISI Web of Science, LILACS, the Cochrane Library and ClinicalTrial.gov) and manual searches up to November 2023. Populations, treatments, and outcome data were combined. Efficacy was assessed based on symptom score (SS) and medication score (MS), measured as standardized mean difference (SMD) or mean difference (MD).

Results from 5 RCTs comprising 1468 patients revealed a significant reduction in SS (SMD, -0.36; 95%confidence interval [CI], - 0.52 to -0.19; P < 0.05) and MS (SMD, -0.29; 95%CI, -0.40 to -0.19; P < 0.05) compared to placebo. The difference of -0.36 SMD for SS corresponds to a MD of -1.26 SS points, greater than the minimal important difference. Subgroup analysis did not show differences in efficacy according to age, asthma status, and geographic location of the study (USA, Canada, Europe, Russia). No safety issues were reported.

This product-specific meta-analysis reinforces the evidence of clinical benefits associated with the 300 IR 5-grass SLIT tablet, suggesting its appropriateness as a therapeutic choice for patients with ARC, irrespective of concurrent asthma, and exhibiting a favorable safety profile.

Allergen immunotherapy (AIT) aims at modulating the immune response by administration of allergen preparations at regular intervals over several years (1). For subcutaneous AIT (SCIT), the treatment is initiated with a dose escalation phase followed by a maintenance dose administration. Over the last decade, there has been a trend towards shortening dose escalation regimens to increase patient adherence. This open-label, phase II trial aimed to investigate the safety and tolerability of a house dust mites (HDMs) SCIT product when used in a newly designed one-strength dose escalation scheme.

Patients, aged 12-65, suffering from HDM-allergic rhinitis/rhinoconjunctivitis ± asthma were included. Patients were randomized to the one-strength (6 injections from the highest strength 3) or the Standard dose escalation regimen (14 injections from strengths 1 to 3) using the HDMs-SCIT product. All adverse events were reported. Tolerability was assessed on the Likert scale.

One hundred and forty-three patients were randomized, 79 adults and 64 adolescents. In total, the one-strength regimen caused more adverse drug reactions (ADRs) than the Standard regimen (p = .0457). With both regimens most ADRs were local reactions which occurred more often in the one-strength group (p = .0393). But there was no significant difference in the number of patients affected by systemic or serious ADRs between both regimens. No relevant differences occurred between the two age groups and no other risks were observed for adolescents compared to adults.

The safety and tolerability of both regimens can be considered comparable, as most ADRs were local reactions, primarily rated as mild in intensity. Nevertheless, the one-strength regimen caused more ADRs. Reducing the number of injections from 14 to 6 while using only one strength offers the potential to improve patient adherence which further might increase clinical efficacy. Future trials could confirm this hypothesis.

Pollen-food-allergy syndrome (PFAS) is common among patients with allergic rhinitis. Treatment recommendations for patients with PFAS remain variable.

To develop consensus recommendation statements for managing patients with PFAS.

An international panel of allergists, researchers, and nutritionists with an interest in PFAS from 25 different institutions across 11 countries convened and a list of statements was written by 3 authors. The RAND/University of California Los Angeles methodology wasadopted to establish consensus on the statements.

After 2 Delphi rounds, a consensus was reached on 14 statements. The panel agreed that patients with PFAS would benefit from counseling on the nature and basis of PFAS and the rare chance of more severe systemic reactions and their recognition. The panel agreed on avoiding the raw food responsible for the index reaction, but not potentially cross-reactive fruits/vegetables based on the responsible food of the index reaction. Epinephrine autoinjectors should be recommended for patients with PFAS who experienced severe symptoms (beyond the oropharynx) or for patients considered at risk for severe reactions. The panel agreed that the benefit of allergen immunotherapy remains unclear and that PFAS should not be considered the primary indication for such intervention.

We developed consensus statements regarding counselling patients about the nature and severity of PFAS, potential risk factors, dietary avoidance, epinephrine autoinjector prescription, and allergen immunotherapy consideration for patients with PFAS.

As there is much controversy in using intralymphatic immunotherapy (ILIT) as a therapeutic means for allergic rhinitis (AR), its efficacy and safety for AR were investigated based on a systematic review and meta-analysis.

Databases PubMed, Embase, Cochrane library, and Web of Science were employed to retrieve relevant randomized control studies on ILIT for AR. The search deadline was September 15, 2023. Meta-analysis was performed on the data of the included literature using Stata 15.0.

Eleven randomized control studies were included involving a total of 406 patients. Meta-analysis results revealed that ILIT improved patients' quality of life [standardized mean difference (SMD) = -0.53, 95% confidence interval (CI) = (-1.00, -0.050)], and reduced the adverse events of nasal symptoms [risk ratio (RR) = 0.16, 95% CI = (0.06, 0.45)] as compared to control, whereas no significant difference was discovered in symptom score [SMD = 0.14, 95% CI = (-0.34, 0.62)], IgE [SMD = 0.93, 95% CI = (-0.44, 2.30)], medication scores [SMD = 1.37, 95% CI = (-0.45, 3.18)], comprehensive symptom and medication scores [SMD = 0.93, 95% CI = (-0.62, 2.47)], nasal symptoms [RR = 0.16, 95% CI = (0.06, 0.45)], and lymphadenectasis [RR = 2.27, 95% CI = (0.37, 6.73)] versus control.

After the application of the ILIT strategy against AR, the quality of life of patients was improved and the incidence of adverse events associated with nasal symptoms was reduced, but the conclusion needed further verification with more high quality research.

Allergen Immunotherapy (AIT) is the only etiological therapeutic method available for allergic rhinitis (AR). Currently, several options for AIT in the market, such as subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT), have different routes of administration. These traditional methods have achieved encouraging outcomes in clinic. However, the side effects associated with these methods have raised the need for innovative approaches for AIT that improve safety, shorten the course of treatment and increase local drug concentration. Nanoparticles (NPs) are particles ranging in size from 1 to 100 nm, which have been hired as potential adjuvants for AIT. NPs can be employed as agents for modulating immune responses in AR or/and carriers for loading proteins, peptides or DNA molecules. This review focuses on different kinds of nanoparticle delivery systems, including chitosan nanoparticles, exosomes, metal nanoparticles, and viral nanoparticles. We summarized the advantages and limitations of NPs for the treatment of allergic rhinitis. Overall, NPs are expected to be a therapeutic option for AR, which requires more in-depth studies and long-term therapeutic validation.

Hymenoptera venom allergy is a public health issue and has an undeniable impact on quality of life. Allergen immunotherapy (AIT) has shown long-term efficacy in this severe and potentially lethal allergy. However, no biomarker can predict the effectiveness of this treatment.

We evaluated the contribution of IgE blocking activity, a functional biomarker carried out in our center using flow cytometry, to predict the efficacy of AIT.

This retrospective study from 1985 to 2022 describes in detail the demographic, clinical, and biological characteristics of patients who benefited from AIT with Hymenoptera venom at the University Hospital of Limoges. The outcome measure used was the presence of anaphylactic reaction (grade I to IV according to Ring and Messmer) in case of a new sting after discontinuation of AIT.

Our study, mainly composed of patients allergic to Vespula wasp venom, did not emphasize the interest of IgE blocking activity in the prediction of a relapse after a new sting. However, this inhibition showed a significant correlation with the amount of IgG4 antibodies.

There is no biomarker that can help make the decision of stopping AIT. However, low levels of IgE blocking activity may suggest a likelihood of relapse. Serum IgG4, in correlation with IgE blocking activity, could be useful for monitoring treatment response. Additional studies are necessary to gain a thorough understanding of the composition of inhibitory antibodies.

Allergy immunotherapy (AIT), a treatment approach for allergic rhinitis (AR), is recognized for its potential to modify the disease course beyond mere symptom relief. Interleukin 36γ (IL-36γ), a key player in immune responses, has been implicated in promoting eosinophilic inflammation in AR by activating eosinophils. We aimed to investigate the effect of IL-36γ on group II lymphoid cell (ILC2) in AR patients who underwent sublingual immunotherapy (SLIT).

Twenty-four AR patients were enrolled and administered with SLIT. Serum proteins of IL-36γ, interleukin-5 (IL-5), and interleukin-13 (IL-13) during SLIT were quantitatively assessed using enzyme-linked immunosorbent assay (ELISA). The proportion of ILC2 was determined by flow cytometry. Sorted ILC2s were stimulated by IL-36γ and ILC2 cell differentiation, and type II cytokines expression were examined.

SLIT treatment decreased the serum protein levels of IL-36γ, IL-5, IL-13, and the proportion of ILC2 significantly. IL-36γ suppressed the proliferation of ILC2 by inhibiting the levels of ILC2 transcription factor. IL-36γ also inhibited IL-5 and IL-13 expression from ILC2.

The changes of IL-36γ during SLIT were related to the inhibited function of ILC2, implying that IL-36γ may be used as a new biomarker for monitoring the efficacy of SLIT in AR.