Local Allergic Rhinitis.

Local allergic rhinitis (LAR) is defined by a clinical history suggestive of allergic rhinitis (AR), negativity of systemic IgE measurement and positive response to nasal allergen challenge (NAC). The term local respiratory allergy includes LAR, local allergic asthma (positive response in bronchial allergen challenge) and dual allergic rhinitis defined by the coexistence of AR and LAR. LAR worsens in severity and presence of comorbidities over time, and it is an independent entity from AR. Prevalence is higher in Mediterranean countries. LAR onset occurs during childhood in 36% of cases. Physiopathological features of LAR are: increased nasal eosinophilic inflammation, tryptase and eosinophil cationic protein, and presence of nasal specific IgE in secretions of 20-40% of subjects. A recent study demonstrated increase in sequential class switch recombination to IgE markers in mucosa of LAR with accumulation of IgE+ CD38+ plasmablasts. Moreover, there is increased expression in B cells of mucosal homing receptors CXCR3+ and CXCR4 in peripheral blood, with accumulation of Th9 and Th2 cells. NAC is the gold standard in the diagnosis of LAR. The measurement of specific IgE in nasal secretions basophil activation test or are still not suitable for diagnosis. There is ample evidence of the usefulness of allergen immunotherapy in the treatment in LAR after 4 DBPCRT in 152 patients. In conclusion, knowledge about LAR is continuously increasing, with detailed definition of physiopathological mechanisms and new phenotypes. More awareness of the disease should be promoted among different specialists, and NAC must be considered an essential diagnostic tool in any age group, including children.

Nasal allergen challenge (NAC): Practical aspects and applications from an EU/US perspective-a Work Group Report of the AAAAI Rhinitis, Rhinosinusitis and Ocular Allergy Committee.

Nasal allergen challenge (NAC) is applied in a variety of settings (research centers, specialty clinics, and hospitals) as a useful diagnostic and research tool. NAC is indicated for diagnosis of seasonal and perennial allergic rhinitis, local allergic rhinitis, and occupational rhinitis; to design the composition of allergen immunotherapy in patients who are polysensitized; and to investigate the physio-pathological mechanisms of nasal diseases. NAC is currently a safe and reproducible technique, although it is time- and resource-consuming. NAC can be performed by a variety of methods, but the lack of a uniform technique for performing and recording the outcomes represents a challenge for those considering NAC as a clinical tool in the office. The availability of standardized allergens for NAC is also different in each country. The objective of this workgroup report is to review the current information about NAC, focusing on the practical aspects and application for diagnosis of difficult rhinitis phenotypes (eg, local allergic rhinitis, occupational rhinitis), taking into account the particular context of practice in the United States and the European Union.

Sequential class switch recombination to IgE and allergen-induced accumulation of IgE+ plasmablasts occur in the nasal mucosa of local allergic rhinitis patients.

BACKGROUND: The involvement of allergen-specific (s)IgE in local allergic rhinitis (LAR) has been debated. Here, we investigate the effect of nasal allergen challenge with Dermatophagoides pteronyssinus (NAC-DP) in mucosal and peripheral B-cell subpopulations in LAR patients. METHODS: Nine LAR, 5 allergic rhinitis (AR), and 5 non-atopic healthy control (HC) individuals were subjected to a 3-day NAC-DP protocol, and nasal biopsies and blood samples were collected before and after provocation. Nasal biopsies were used for immunohistochemistry and gene expression studies, whereas the frequency of lymphocyte subsets and basophil activation test (BAT) were analyzed in blood samples by flow cytometry. sIgG was measured in sera. RESULTS: NAC-DP induced an increase in IgE+ CD38+ plasmablasts in the nasal mucosa of LAR patients, but not in AR or HC individuals. Markers of sequential recombination to IgE (εCSR) (from IgG) were observed in 33% of LAR, 20% of AR, and 0% of HC subjects. NAC-DP increased the proportion of peripheral CD19+ CD20+ CD38+ plasmablasts in AR and LAR patients, but not in HC. Expression of the mucosal homing receptor CXCR3 in peripheral CD19+ CD20+ CD38+ plasmablasts from LAR, AR, and HC individuals was 7%, 5%, and 0.5%, respectively. In vitro DP stimulation increased proliferating CD19+ CD20+ CD38+ plasmablasts in LAR and AR patients, but not in HC. Serum DP-sIgG was higher in LAR and AR patients as compared to HC. BAT was positive in 33%, 100%, and 0% of LAR, AR, and HC subjects, respectively. CONCLUSION: These results suggest that allergen exposure induces the sequential εCSR of IgG+ CD19+ CD20+ CD38+ plasmablasts in the nasal mucosa of LAR patients.

Systematic evaluation of allergic phenotypes of rhinitis in children and adolescents.

BACKGROUND: Three allergic phenotypes of rhinitis have been described in adults: allergic rhinitis (AR), local allergic rhinitis (LAR), and dual allergic rhinitis (DAR, coexistence of AR and LAR). Nevertheless, most centers follow a diagnostic approach only based on skin prick test and serum allergen-specific IgE (collectively called atopy tests, AT). This approach prevents the recognition of LAR and DAR, the diagnosis of which requires a nasal allergen challenge (NAC). Here, we investigate the existence of LAR and DAR phenotypes in children and adolescents, and the misdiagnosis rate associated with a work-up exclusively based on AT. METHODS: Clinical data were obtained during physician-conducted interviews, and AT and NAC were systematically performed in 5- to 18-year-old patients with chronic rhinitis. The misdiagnosis rate was defined as the proportion of cases where AT and NAC results were discordant. RESULTS: A total of 173 patients (mean age 15.1 years, 39.9% male) completed the study. AR (positive AT and NAC), LAR (negative AT and positive NAC), DAR (positive AT and NAC for some allergens and negative AT and positive NAC for other allergens), and non-allergic rhinitis (negative NAC) were diagnosed in 45.7%, 24.9%, 11.6%, and 17.9% of individuals, respectively. The clinical profile was comparable among allergic phenotypes, but allergic patients had a significantly earlier rhinitis onset, higher conjunctivitis prevalence, and more severe disease than NAR individuals. A diagnostic work-up exclusively based on AT misclassified 37.6% of patients. CONCLUSIONS: LAR and DAR represent relevant differential diagnosis in pediatric rhinitis. NAC increases the diagnostic accuracy of clinical algorithms for rhinitis in children and adolescents.

The role of aspirin desensitization followed by oral aspirin therapy in managing patients with aspirin-exacerbated respiratory disease: A Work Group Report from the Rhinitis, Rhinosinusitis and Ocular Allergy Committee of the American Academy of Allergy, Asthma & Immunology.

Aspirin-exacerbated respiratory disease (AERD) is characterized by the clinical triad of chronic rhinosinusitis with nasal polyps, asthma, and an intolerance to medications that inhibit the cycloxgenase-1 enzyme. Patients with AERD on average have more severe respiratory disease compared with patients with chronic rhinosinusitis with nasal polyps and/or asthma alone. Although patients with AERD traditionally develop significant upper and lower respiratory tract symptoms on ingestion of cycloxgenase-1 inhibitors, most of these same patients report clinical benefit when desensitized to aspirin and maintained on daily aspirin therapy. This Work Group Report provides a comprehensive review of aspirin challenges, aspirin desensitizations, and maintenance aspirin therapy in patients with AERD. Identification of appropriate candidates, indications and contraindications, medical and surgical optimization strategies, protocols, medical management during the desensitization, and recommendations for maintenance aspirin therapy following desensitization are reviewed. Also included is a summary of studies evaluating the clinical efficacy of aspirin therapy after desensitization as well as a discussion on the possible cellular and molecular mechanisms explaining how this therapy provides unique benefit to patients with AERD.

Correction to: Benefits and harm of systemic steroids for short- and long-term use in rhinitis and rhinosinusitis: an EAACI position paper.

[This corrects the article DOI: 10.1186/s13601-019-0303-6.].

Local allergic rhinitis: a pediatric perspective.

Local allergic rhinitis (LAR) is a differentiated rhinitis phenotype defined by perennial or seasonal rhinitis symptoms without systemic atopy. The diagnosis can be made by a positive response to the nasal allergen challenge (NAC) (the gold standard for diagnosis) in the absence of skin prick test and/or serum allergenspecific immunoglobulin E. Clinical and epidemiological studies have demonstrated that LAR affects individuals from different countries, races, and age ranges. Several studies have shown that the onset of nasal symptoms occurs during childhood in a significant proportion of LAR individuals. Evidence of LAR has been growing, especially in pediatric and Asian populations. A review of the literature reveals that most LAR studies of pediatric populations have appeared in the last three years. The prevalence of LAR in children ranges from 3.7% to 66.6%, and similar to what has been observed in adults, prevalence is higher in Western countries. Publications have shown that LAR in children can be either seasonal or perennial, and diagnosis of LAR confirmed by NAC have been reported with numerous allergens (house dust mites, pollens, molds, and dander). These findings illustrate that LAR is an important differential diagnosis in children with presumed non-allergic rhinitis, and a through review of the very recent literature can contribute to the clinical identification and diagnosis of LAR in children with no evidence of systemic atopy, as well as update readers` knowledge of the topic.

FENOMA Study: Achieving Full Control in Patients with Severe Allergic Asthma.

INTRODUCTION: A Spanish real-world study in patients with severe persistent asthma who achieved asthma control after a one-year treatment with omalizumab highlighted the phenotypic heterogeneity of these patients (FENOMA study). In this subanalysis, we describe the clinical improvement in patients with severe allergic asthma in this study (positive skin test and IgE level 30-1500 IU/mL); n=240. PATIENTS AND METHODS: FENOMA was an observational, multicentre, retrospective study in 345 patients achieving asthma control according to Spanish guidelines (GEMA). Baseline demographic and asthma-related characteristics were collected. Outcomes analyzed were those included in asthma control definition plus changes in background treatments and in blood eosinophil count (%) and exhaled nitric oxide fraction [FeNO]. RESULTS: At baseline, patients were aged 45.4±15.0 years; 67% were women. Median (Q1;Q3) IgE levels were 302.5 (154.0; 553.5) IU/mL. After one-year treatment with omalizumab: 43.3% of patients had daytime symptoms vs 97.7% before treatment and 49.6% stopped taking oral corticosteroids. FEV1 increased a median of 12.0 (4.0; 23.0)%; P <0.0001. The number of non-severe asthma exacerbations decreased a median of -4.0 (-7.0; 2.0); P <0.0001. Median unplanned visits to primary care or specialists and days of school/workplace absenteeism decreased from 4.9 (2.0; 6.0), 1.0 (0.0; 3.0) and 0.0 (0.0; 14.0) to 0.0 (0.0; 1.0), 0.0 (0.0; 0.0) and 0.0 (0.0; 0.0), respectively. Median eosinophil blood count and FeNO decreased from 5.0 (3:0; 8.0)% to 3.0 (2.0; 5.5)% and from 36.0 (23:0; 53.0) ppb to 20.0 (13.0; 34.0) ppb, respectively. CONCLUSION: This study highlights the asthma control achieved by patients with severe allergic asthma treated with omalizumab, with relevant benefits on the burden of the disease both on patients and the healthcare system.

Coexistence of nasal reactivity to allergens with and without IgE sensitization in patients with allergic rhinitis.

BACKGROUND: Allergic rhinitis (AR) and local allergic rhinitis (LAR) are defined by nasal reactivity to aeroallergens with and without positive skin prick test (SPT), respectively. In this study, we aimed to investigate whether both types of allergen-specific reactivity can coexist in the same individual. METHODS: Forty-eight patients with perennial rhinitis symptoms and positive SPT with seasonal allergens only (discrepant group) were subjected to consecutive nasal allergen challenges (NAC) with seasonal (NAC-S) and perennial allergens (NAC-P). A nasal lavage was collected before and after the NACs to measure eosinophil cationic protein (ECP). A basophil activation test (BAT) with seasonal and/or perennial allergens was performed in ten patients from the discrepant group and in six seasonal allergic rhinitis (SAR), eight perennial local allergic rhinitis (LAR), six nonallergic rhinitis (NAR), and six healthy control (HC) individuals. RESULTS: All patients in the discrepant group tested positive in the NAC-S, and 41 of them (85.4%), also in the NAC-P (group A). Conversely, seven patients tested negative in the NAC-P (group B). ECP in the nasal lavage increased after the NAC-P in the group A (P = .004), but not in the group B. The BAT with seasonal allergens was positive in 100% of SAR and group A cases, whereas the BAT with perennial allergens was positive in 37.5% and 60% of LAR and group A cases, respectively. All NAR and HC subjects tested negative for the BAT. CONCLUSION: This study shows that nasal reactivity to aeroallergens with and without positive SPT can coexist in the same patient. We propose the term dual allergic rhinitis for this rhinitis phenotype.

Benefits and harm of systemic steroids for short- and long-term use in rhinitis and rhinosinusitis: an EAACI position paper.

Because of the inflammatory mechanisms of most chronic upper airway diseases such as rhinitis and chronic rhinosinusitis, systemic steroids have been used for their treatment for decades. However, it has been very well documented that-potentially severe-side-effects can occur with the accumulation of systemic steroid courses over the years. A consensus document summarizing the benefits of systemic steroids for each upper airway disease type, as well as highlighting the potential harms of this treatment is currently lacking. Therefore, a panel of international experts in the field of Rhinology reviewed the available literature with the aim of providing recommendations for the use of systemic steroids in treating upper airway disease.

Severe asthma phenotypes in patients controlled with omalizumab: A real-world study.

BACKGROUND: The appropriate identification of asthma phenotypes of responders to omalizumab would optimize the selection of treatment. OBJECTIVE: To describe the most frequent clinical phenotypes in patients with severe asthma responding to omalizumab and their clinical and pulmonary function improvement. METHODS: This was an observational, retrospective, multicenter study. Adult patients with severe asthma, who achieved good control after the first year of treatment with omalizumab were included. Omalizumab was prescribed according to clinical routine practice. Responders were assigned to one pre-established phenotype based on the most predominant one before they had started treatment with omalizumab, all according to the physician's criteria. Data about asthma symptoms, number of non-severe asthma exacerbations, medication intake (inhaled and oral corticosteroids and rescue medication), lung function, high fractional exhaled nitric oxide (FeNO) and peripheral eosinophils counts were recorded. RESULTS: Among the 345 patients included, the main phenotypes were severe asthma with frequent exacerbations (29.9%), early-onset allergic asthma (23.8%), severe steroid-dependent asthma (18.8%), and severe eosinophilic asthma (13.6%). Clinical and respiratory changes observed after first year of treatment with omalizumab included: reduction in asthma symptoms, reduction in the use and dose of corticosteroids and need for rescue therapy, improvement of pulmonary function, reduction in the number of episodes of non-severe asthma exacerbations regardless of the duration of severe disease since the diagnosis. Increased blood levels of peripheral eosinophils and high FeNO levels were found at baseline. CONCLUSION: Several heterogeneous severe asthma phenotypes were observed as good responders to omalizumab.

How to Diagnose and Treat Local Allergic Rhinitis: A Challenge for Clinicians.

Chronic rhinitis is a very common disease that can be divided in various phenotypes. Historically, the condition has been classified into the allergic rhinitis (AR) and non-allergic non-infectious rhinitis (NAR) forms, based on the results of the classical biomarkers of atopy: skin prick test and serum allergen-specific IgE However, this classification does not reflect the complexity of the rhinitis syndrome, as illustrated by the existence of non-atopic rhinitis patients who display a nasal reactivity to environmental allergens. This new phenotype has been termed local allergic rhinitis (LAR) and can be only recognized if an additional test such as the nasal allergen challenge (NAC) is integrated in the diagnostic algorithm for chronic rhinitis. Recent data shows that the NAC is a very safe and reliable technique ready for the clinical practice. LAR is a differentiated rhinitis phenotype which often commences during childhood and quickly progresses towards a clinical worsening and the association of comorbidities in other mucosal organs. Recent evidence supports the existence of a bronchial counterpart of LAR (local allergic asthma), which highlights the pathophysiological links between the upper and lower airways and reinforces the united airways concept. Importantly, several controlled studies have demonstrated the ability of allergen immunotherapy to control LAR symptoms while the therapy is being administered. This review emphasizes the need to implement the NAC in the clinical practice in order to facilitate the recognition of LAR patients, allowing for an early prescription of specific therapies with disease-modifying potential.

Bronchial asthma triggered by house dust mites in patients with local allergic rhinitis.

BACKGROUND: Over 30% of local allergic rhinitis (LAR) patients self-report bronchial symptoms suggestive of asthma, but the relationship between the allergen exposure and the bronchial symptoms has not been studied. OBJECTIVE: To investigate whether a bronchial counterpart of LAR exists. METHODS: Patients were classified by clinical history, skin prick test/serum specific IgE (sIgE), and nasal allergen provocation test (NAPT) into the LAR, allergic rhinitis (AR), and nonallergic rhinitis (NAR) phenotypes. Twenty-eight LAR, 18 AR, and 19 NAR patients self-reporting bronchial symptoms suggestive of asthma and 8 healthy controls (HC) were subjected to a methacholine test (MT) before (Visit 1) and 24 hours after (Visit 3) a bronchial provocation test with Dermatophagoides pteronyssinus (BPT-DP) (Visit 2). Induced sputum and peripheral blood obtained after each MT were analyzed for immune cell populations, tryptase, ECP, and sIgE. RESULTS: A positive MT was found in 50% of LAR, 83.3% of AR, 57.89% of NAR, and 0% of HC individuals (P = 0.022 AR vs LAR) at V1. BPT-DP was positive in 8 LAR and 15 AR patients (28% vs 83.3%, P < 0.001), with no positive responses in NAR and HC. All BPT-DP+ patients experienced a significant decrease of PC20 at V3 vs V1 (P = 0.016 LAR, P ≤ 0.001 AR). BPT-DP+ patients also showed a significant increase of eosinophils, monocytes, and ECP in induced sputum at V3 compared with V1. CONCLUSION: The results suggest the existence of a new asthma phenotype (local allergic asthma) defined by absence of systemic atopy and positivity to BPT with allergen.

Eicosanoid mediator profiles in different phenotypes of nonsteroidal anti-inflammatory drug-induced urticaria.

BACKGROUND: The role of arachidonic acid metabolites in NSAID-induced hypersensitivity has been studied in depth for NSAID-exacerbated respiratory disease (NERD) and NSAID-exacerbated cutaneous disease (NECD). However, no information is available for NSAID-induced urticarial/angioedema (NIUA), despite it being the most frequent clinical entity induced by NSAID hypersensitivity. We evaluated changes in leukotriene and prostaglandin metabolites for NIUA patients, using patients with NECD and single-NSAID-induced urticaria/angioedema or anaphylaxis (SNIUAA) for comparison. METHODS: Urine samples were taken from patients with confirmed NSAID-induced urticaria and healthy controls, at baseline and at various time intervals after ASA administration. Eicosanoid measurement was performed using high-performance liquid chromatography-tandem mass spectrometry and gas chromatography-mass spectrometry. RESULTS: No differences were found between groups at baseline. Following ASA administration, LTE4 and 9α,11ß-PGF2 levels were increased in both NIUA and NECD patients compared to baseline, rising initially, before decreasing toward initial levels. In addition, the levels of these metabolites were higher in NIUA and NECD when compared with the SNIUAA and control groups after ASA administration. No changes were found with respect to baseline values for SNIUAA and control groups. CONCLUSIONS: We present for the first time data regarding the role of COX-1 inhibition in NIUA. Patients with this entity show a similar pattern eicosanoid levels following ASA challenge to those with NECD. Further studies will help ascertain the cell populations involved and the underlying molecular mechanisms.

Safety and reproducibility of nasal allergen challenge.

BACKGROUND: The nasal allergen challenge (NAC) is a useful tool for the diagnosis of allergic rhinitis (AR) and local allergic rhinitis (LAR) and might serve to design and monitor allergen immunotherapy. Nevertheless, data about its safety and reproducibility are scarce. OBJECTIVE: To investigate the safety and reproducibility of NAC in pediatric and adult rhinitis patients with/without asthmatic symptoms, and in healthy controls. METHODS: A retrospective evaluation of the NACs conducted in our Unit for 2005-2017 and monitored by acoustic rhinometry and nasal-ocular symptoms was performed to analyze the safety of two methods for allergen application (metered spray & micropipette) and NAC protocols (NAC with single or multiple allergens/session [NAC-S & NAC-M]). The adverse events (AEs), spirometry values, and rescue medication required for AE were recorded. The reproducibility was examined by a prospective analysis of three repeated NAC-S performed at 1-2-month interval in AR, LAR and nonallergic rhinitis patients, and in healthy controls. RESULTS: A total of 11 499 NACs were performed in 518 children and 5830 adults. Only four local AE occurred, and 99.97% of NACs were well tolerated. The reproducibility and positive and negative predictive values of three consecutive NAC-S performed in 710 subjects were 97.32%, 100%, and 92.91%, respectively. There were no false-positive results in the 710 analyzed subjects. Safety and reproducibility were comparable between the methods of allergen application and the rhinitis phenotypes. CONCLUSION: The NAC is a safe and highly reproducible diagnostic test ready to be used in the clinical practice in both children and adults with or without asthma.

IgE Test in Secretions of Patients with Respiratory Allergy.

PURPOSE OF REVIEW: IgE is a key player in multiple inflammatory airway diseases. Ample literature demonstrates its presence in mucosa of patients with allergic rhinitis (AR), local allergic rhinitis (LAR), asthma, or chronic rhinosinusitis with nasal polyposis (CRSwNP). RECENT FINDINGS: Current evidence shows that high-affinity IgE in blood stream of allergic individuals derives mainly from the mucosae. Also, mucosal synthesis of IgE can occur in the absence of systemic atopy, and may be relevant in atopic and non-atopic phenotypes of rhinitis as demonstrated in LAR. Specific IgE (sIgE) detection varies depending on technique used for sample collection and its measurement. sIgE detection is highly specific for diagnosis of LAR. Moreover, measurement of sIgE in secretions could be useful in monitoring response to allergen-specific immunotherapy in both AR and LAR phenotypes. This review will focus on recent developments in the role of IgE in respiratory diseases, and the clinical implications of its measurement in secretions.

Asthma and allergic rhinitis associate with the rs2229542 variant that induces a p.Lys90Glu mutation and compromises AKR1B1 protein levels.

Asthma and rhinitis are two of the main clinical manifestations of allergy, in which increased reactive oxygen or electrophilic species can play a pathogenic role. Aldose reductase (AKR1B1) is involved in aldehyde detoxification and redox balance. Recent evidence from animal models points to a role of AKR1B1 in asthma and rhinitis, but its involvement in human allergy has not been addressed. Here, the putative association of allergic rhinitis and asthma with AKR1B1 variants has been explored by analysis of single-strand variants on the AKR1B1 gene sequence in 526 healthy subjects and 515 patients with allergic rhinitis, 366 of whom also had asthma. We found that the rs2229542 variant, introducing the p.Lys90Glu mutation, was significantly more frequent in allergic patients than in healthy subjects. Additionally, in cells transfected with expression vectors carrying the wild-type or the p.Lys90Glu variant of AKR1B1, the mutant consistently attained lower protein levels than the wild-type and showed a compromised thermal stability. Taken together, our results show that the rs2229542 variant associates with asthma and rhinitis, and hampers AKR1B1 protein levels and stability. This unveils a connection between the genetic variability of aldose reductase and allergic processes.

Is the evidence of local allergic rhinitis growing?

PURPOSE OF REVIEW: To examine the recent advances on epidemiological studies, diagnostic approach and clinical management of local allergic rhinitis (LAR) in adults and children. RECENT FINDINGS: Evidence about LAR is growing especially in pediatric and Asian populations. The prevalence of LAR is lower in Asian countries compared with western countries in both children and adults. LAR is considered a chronic condition and an independent rhinitis phenotype that affects up to 26.5% of nonatopic rhinitis patients. The disease rapidly progress toward the clinical worsening with associated onset of asthma and conjunctivitis, which further impairs patient's quality of life. Nasal Allergen Provocation Test is the diagnostic gold standard that can be complemented by basophil activation test and the detection of specific IgE in nasal secretions. Allergen immunotherapy induces a significant and early improvement in both clinical symptoms and quality of life in LAR patients. SUMMARY: LAR is a common entity, with different prevalence depending on geographical locations. LAR has to be considered in the process of differential diagnosis in children and adults with rhinitis. Diagnosis of LAR is crucial in order to start an etiologic treatment such as allergen immunotherapy, which has proven to be very effective in these patients.

Immunological Changes Induced in Peach Allergy Patients with Systemic Reactions by Pru p 3 Sublingual Immunotherapy.

SCOPE: Sublingual immunotherapy using peach extract enriched in Pru p 3 (Pru p 3-enriched-SLIT) brings a new perspective to treating patients with allergy to lipid transfer proteins. We evaluate the immunological changes induced by Pru p 3-enriched-SLIT during one year. METHODS AND RESULTS: Three groups are included: peach allergic patients who receive Pru p 3-enriched-SLIT, peach allergic untreated patients, and controls. Peripheral blood mononuclear cells are obtained before treatment and at different time-points. Monocyte-derived dendritic cells (moDCs) maturation and lymphocyte proliferation are assessed by flow cytometry. Data showed a significant reduction of moDCs maturation status during one year of treatment and an increase in PD-L1. Moreover, we observed a significant decrease of the Pru p 3-specific proliferation of effector cells and an increase in regulatory T (Treg) cells with higher PD-L1 expression and IL-10 production. These are observed in patients treated only. CONCLUSION: Successful Pru p 3-enriched-SLIT is linked to an important immunosuppression of allergen-specific effector T cells, potentially due to an increase of allergen-specific Treg cells. These cellular changes are orchestrated by the activity of moDCs promoting the expression of PD-L1 that will participate in the regulatory response. These changes may serve as biomarkers during SLIT alongside other features such as IgE/IgG4 ratio.