Allergen immunotherapy (AIT) is a disease-modifying treatment for IgE-mediated diseases. Randomized controlled trials (RCTs) support AIT's potential role in asthma prevention but evidence from non-randomized studies of interventions (NRSI) and longitudinal observational studies has been poorly addressed. Therefore, we aimed to conduct a systematic review and meta-analysis to assess clinical data from all study types to evaluate quantitatively the preventive role of AIT in asthma onset.

We search three databases. Studies were screened, selected and evaluated for quality using risk-of-bias (ROB) tools. Data were descriptively summarized and meta-analysed using random effects. We performed a sensitivity, influence and subgroup analyses. Publication bias and heterogeneity were assessed.

From the 4549 identified studies, 24 (12 RCTs and 12 NRSI) were included in the qualitative synthesis and 18 underwent metaanalysis. One study was at low ROB, seven had moderate ROB, and 15 were proven of high ROB. Random-effects analysis showed a significant decrease in the risk of developing asthma following AIT by 25% (RR, 95% CI: 0.75, 0.64-0.88). This effect was not significant in the sensitivity analysis. Publication bias raised concerns, together with the moderate heterogeneity between studies (I2 = 58%). Subgroup analysis showed a remarkable preventive effect of AIT in children (RR, 95% CI: 0.71, 0.53-0.96), when completing 3 years of therapy (RR, 95% CI: 0.64, 0.47-0.88), and in mono-sensitized patients (RR, 95% CI: 0.49, 0.39-0.61).

Our findings support a possible preventive effect of AIT in asthma onset and suggest an enhanced effect when administered in children, mono-sensitized, and for at least 3 years, independently of allergen type.

The PALISADE study, an international, phase 3 trial of peanut oral immunotherapy (POIT) with AR101, resulted in desensitization in children and adolescents who were highly allergic to peanut. An improved understanding of the immune mechanism induced in response to food allergen immunotherapy would enable more informed and effective therapeutic strategies. Our main purpose was to examine the immunological changes in blood samples from a subset of peanut allergic individuals undergoing oral desensitization immunotherapy with AR101.

Blood samples obtained as part of enrollment screening and at multiple time points during PALISADE study were used to assess basophil and CD4+ T-cell reactivity to peanut.

The absence of clinical reactivity to the entry double-blinded placebo controlled peanut challenge (DBPCFC) was accompanied by a significantly lower basophil sensitivity and T-cell reactivity to peanut compared with DBPCFC reactors. At baseline, peanut-reactive TH2A cells were observed in many but not all peanut-allergic patients and their level in peripheral blood correlates with T-cell reactivity to peanut and with serum peanut-specific IgE and IgG4 levels. POIT reshaped circulating peanut-reactive T-cell responses in a subset-dependent manner. Changes in basophil and T-cell responses to peanut closely paralleled clinical benefits to AR101 therapy and resemble responses in those with lower clinical sensitivity to peanut. However, no difference in peanut reactive Treg cell frequency was observed between groups.

Oral desensitization therapy with AR101 leads to decreased basophil sensitivity to peanut and reshapes peanut-reactive T effector cell responses supporting its potential as an immunomodulatory therapy.

There is a need for a fast, efficient and safe way to induce tolerance in patients with severe allergic rhinitis. Intralymphatic immune therapy has been shown to be effective.

Patients with severe birch and timothy allergy were randomized and received three doses of 0.1 ml of birch and 5-grass allergen extracts (10,000 SQ units/ml, ALK-Abelló), or birch and placebo or 5 grass and placebo by ultrasound-guided injections into inguinal lymph nodes at monthly intervals. Rhinoconjunctivitis total symptom score, medication score and rhinoconjunctivitis quality of life questionnaire were evaluated before treatment and after each birch and grass pollen season during three subsequent years. Circulating proportions of T helper subsets and allergeninduced cytokine and chemokine production were analysed by flow cytometry and Luminex.

The three groups reported fewer symptoms, lower use of medication and improved quality of life during the birch and grass pollen seasons each year after treatment at an almost similar rate independently of treatment with one or two allergens. Mild local pain was the most common adverse event. IgE levels to birch decreased, whereas birch-induced IL-10 secretion increased in all three groups. IgG4 levels to birch and timothy and skin prick test reactivity remained mainly unchanged. Conjunctival challenge tests with timothy extract showed a higher threshold for allergen. In all three groups, regulatory T cell frequencies were increased 3 years after treatment.

Intralymphatic immunotherapy with one or two allergens in patients with grass and birch pollen allergy was safe, effective and may be associated with bystander immune modulatory responses.

Ragweed allergen causes Allergic rhinoconjunctivitis and sublingual immunotherapy is one of the treatment modalities to desensitize allergic individuals. This systematic review assesses the effectiveness and safety of sublingual immunotherapy for allergic rhinoconjunctivitis caused due to Ragweed.

The databases search was done through December 2020. English language randomized controlled trials were included if they compared sublingual immunotherapy with placebo, pharmacotherapy, or other sublingual immunotherapy regimens, and reported clinical outcomes. The strength of the evidence for each comparison and outcome was graded based on the risk of bias, consistency, magnitude of effect, and the directness of the evidence.

The searches performed according to the protocol identified 134 abstracts of which 67 were duplicates. A total of 37 full papers were therefore reviewed of which 5 were included for the final study. Participants' ages ranged from 4 to 58 years. The risk of bias was low in most studies. The review suggests that sublingual immunotherapy improves rhinoconjunctivitis symptoms, with 4 of 4 studies reporting efficacy showed improvement in the symptom score of SLIT groups compared to placebo. Local reactions were frequent, but anaphylaxis was not reported in any of the studies. Serious adverse events were very few in all the studies.

The overall evidence showed the effectiveness of sublingual immunotherapy for the treatment of allergic rhinoconjunctivitis with or without asthma, but high-quality studies are still needed to answer questions regarding optimal dosing strategies.

Previous studies involving predominantly adults concluded that the patients developing frequent large local reactions (LLRs) might be at greater risk for systemic reactions (SRs) during subcutaneous allergen immunotherapy (SCIT).

To determine the rate of side effects to SCIT and evaluate frequency of LLR among pediatric patients with SRs.

The retrospective study included pediatric patients receiving SCIT. Data on the demographic features, season at onset of SCIT, the indication for treatment, additional allergic diseases, laboratory results, the allergens applied, side effects after injection, grade of SRs, and the total number of injections for each patient were collected retrospectively from the medical records and injection charts.

A total of 19,562 injections were administered to 261 patients with conventional SCIT. The incidence LLRs was 0.2% per injection; 1.15% of all patients (n = 3) experienced LLRs on at least two consecutive visits. Systemic side effects were seen in 1% of all SCIT injections. No grade 3 or grade 4 SRs were observed. Logistic regression analysis showed that having an LLR was 3.32 times (95% CI, 1.313-8. 440; P = 0.011) and initiation of SCIT in summer and spring was 4.309 and 3.056 times than autumn (95% CI, 1.527-12.157, P = 0.006; 95% CI, 1.358-6.849, P = 0.007), respectively, increased risk for an SR.

Having LLRs might predict the risk of SRs at any time during immunotherapy in also pediatric patients. Knowing the risk factors is important for developing a personalized protocol in these patients.

To compare systemic allergen sensitivity and local allergen sensitivity in the sinonasal tissue of patients with a recently identified subtype of chronic rhinosinusitis strongly associated with allergy: central compartment atopic disease (CCAD).

Prospective cohort study.

Academic tertiary care rhinology clinic.

Fifteen participants with endoscopic and radiographic evidence of CCAD underwent systemic allergy testing with skin testing and measurement of serum specific immunoglobulin E (sIgE) to 15 regionally common aeroallergens. Local allergen sensitivity was determined by measuring sIgE to these same 15 allergens in their sinonasal tissue. sIgE testing was performed by ImmunoCAP assay.

Of the 15 participants, 14 were sensitive to at least 1 allergen locally in the central compartment and systemically on skin or serum testing. Among all participants, 4 were sensitive to allergens on central compartment sIgE testing that they were not sensitive to on skin and serum sIgE testing (range, 1-8 discordant allergens). Comparisons between local and systemic aeroallergen sensitivity results showed statistically significant correlations (P < .05) ranging from weak to strong.

Systemic allergy testing is recommended in the initial workup for CCAD. Local allergen sensitivities may be present in a subset of patients with CCAD. Further study of the clinical significance of these sensitivities should be undertaken in CCAD, with evaluation of the role of medical therapies and allergen immunotherapy in the treatment of CCAD.

Vespa velutina nigrithorax (VVN), typically known as the Asian yellow-legged wasp, has been one of the most significant invasive species in western Europe since 2010. Currently, VVN has become the most prevalent cause of Hymenoptera anaphylaxis in the north and northwestern Spain. For this reason, it is crucial to diagnose anaphylaxis cases in the acute moment for carrying out the best available treatment as soon as possible.

To achieve a complete understanding of the venom allergen composition that will help to develop efficient diagnostics and immunotherapy treatments on the basis of this venom.

In this study, autochthonous VVN venom was obtained and characterized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, isoelectric focusing, followed by a mass spectrometry analysis. In addition, the allergenic sensitization profile of patients diagnosed with allergy to VVN in the Allergology Service of Navarra University Hospital between the years 2017 and 2020 was studied by immunoblotting and specific IgE (ImmunoCAP, Thermo Fisher Scientific, Uppsala, Sweden).

Two new allergens (dipeptidyl peptidase IV and serin protease) were identified in the autochthonous VVN venom, and their identity was confirmed by liquid chromatography-mass spectrometry analysis. The study by ImmunoCAP using sera from 12 patients who had a systemic reaction after a VVN sting revealed groups 5 and 1 as predominant allergens (92% and 34%, respectively). Furthermore, the immunoblotting assay recognized dipeptidyl peptidase IV (50%) in the sera of these patients.

Serine protease and the dipeptidyl peptidase IV are components of the VVN venom, and the latter is an allergen recognized in the studied population.

Venom immunotherapy (VIT) is the only efficient therapy for the Hymenoptera insect venom allergy. Immunotherapy with bee venom is encumbered with a higher risk of systemic side effects and/or therapeutic failures. The objective of the study was to assess if specific profiles of molecular IgE (Immunoglobulin E) responses are associated with an increased risk of systemic side effects and/or the treatment's inefficacy. The study group numbered 64 bee venom allergic patients (BVA) who received venom immunotherapy modo ultra-rush (VIT-UR (f/m: 32/32, mean age 43.4 ± 17.2). In total, 54.84% of them manifested allergic reactions of grades I-III (acc. to Mueller's scale), while 48.66% manifested reactions of grade IV. In all the patients, IgE against bee venom extract, rApi m 1 and tryptase (sBT) were assessed. In 46 patients, assessments of IgE against rApi m 2, 3, 5, 10 were also performed. BVA patients manifesting cardiovascular symptoms (SYS IV0) showed higher levels of both sIgE-rApi m 5 (p = 0.03) and tryptase (p = 0.07) than patients with SYS I-III. Systemic adverse events during VIT with bee venom were more frequent in the induction phase than in the maintenance phase: 15.22% vs. 8.7%. In BVA patients who experienced systemic adverse events during VIT, higher concentrations of sIgE-rApi m 5 (p < 0.05), rApi m 1 (p = 0.009), and sBT (p = 0.019) were demonstrated. We conclude that higher levels of sIgE against rApi m 1, rApi m 5, and tryptase many constitute a potential marker of the severity of allergic reactions and therapeutic complications that can occur during VIT with bee venom.

Pollen-food allergy syndrome (PFAS) usually manifests as an itching sensation in the mouth and throat immediately after eating fresh fruits and vegetables. However, some patients with PFAS experience systemic symptoms including anaphylaxis. In Europe, cypress gibberellin-regulated protein (GRP) has been noted to cause allergenicity and exhibit cross-reactivity with peach GRP. Japanese cedar (Cryptomeria japonica), classified in the cypress family, is the primary causative substance among all environmental allergens in Japan. However, studies on the prevalence of GRP sensitization in patients with cedar pollinosis are lacking.

This study examined the prevalence of GRP sensitization in patients with Japanese cedar pollinosis.

We enrolled 52 patients who had requested sublingual immunotherapy treatment with mild-to-severe rhinitis during spring, and had a JCP specific immunoglobulin E (IgE) levels of >0.7 UA/mL. Peach GRP was purified using affinity chromatography with a monoclonal antibody column. Specific IgE levels to peach GRP were measured using an enzyme-linked immunosorbent assay. Samples exhibiting absorbance at 450 nm of over mean plus three standard deviations of the negative control value were defined as positive. Sera from three patients with severe peach allergy were used as positive controls.

Eleven sera from 52 patients with JCP-induced allergic rhinitis were positive for peach GRP.

Twenty percent of patients with cedar pollinosis were sensitized to peach GRP. Well-powered studies are needed to clarify whether these patients are at an increased risk for systemic symptoms or whether they primarily demonstrate only localized symptoms.

Alternaria is a genus of worldwide fungi found in different habitats such as soil, the atmosphere, plants or indoor environments. Alternaria species are saprobic-largely involved in the decomposition of organic material-but they can also act as animal pathogens, causing disease in humans and animals, developing infections, toxicosis and allergic diseases. A. alternata is considered one of the most important sources of fungal allergens worldwide and it is associated with severe asthma and respiratory status. Among the A. alternata allergens, Alt a 1 is the main sensitizing allergen and its usefulness in diagnosis and immunotherapy has been demonstrated. Alt a 1 seems to define a protein family that can be used to identify related pathogenic fungi in plants and fruits, and to establish taxonomic relationships between the different fungal divisions.