Increased prevalence of Autoimmune Diseases in Children with Chronic Spontaneous UrticariaMichelle Le, MD1, Lydia Zhang MD2, Sofianne Gabrielli MSc2, Connor Prosty BSc, MD(c)1, Laura May Miles LLM, MD(c)2, Elena Netchiporouk, MD, MSc1, Sharon Baum, MD3, Shoshana Greenberger, MD3, Luis F. Ensina, MD, MSc, PhD4, Fatemeh Jafarian, MD1, Xun Zhang, PhD5, Moshe Ben-Shoshan, MD, MSc21Division of Dermatology, McGill University, Montreal, QC, Canada2Division of Pediatric Allergy and Clinical Immunology, Department of Pediatrics, McGill University Health Centre, Montreal, QC, Canada3Department of Dermatology, Chaim Sheba Medical Center, Tel-Aviv University, Sackler School of Medicine, Tel Hashomer, Israel4Department of Pediatrics, Federal University of São Paolo, Brazil5Centre for Outcome Research and Evaluation, Research Institute of McGill University Health Centre, Montreal, QC, CanadaCorrespondence: Michelle Le, M.D., 1001 Decarie Blvd, Montréal, Québec, H4A 3J1 email: email@example.comArticle type: LetterManuscript word count: 981References : 10Tables : 1Figures: NoneFunding sources : NoneConflicts of interest: None declaredIRB Approval Status : Reviewed and approved by McGill University Health Centre; approval 12-255GEN
Levetiracetam (LEV) is a second-generation antiepileptic drug (AED) that is well tolerated, has a broad spectrum of action, low protein binding, and minimal hepatic metabolism. The incidence of hypersensitivity to LEV in children and adults is 0.6%. This is the first reported fixed drug eruption (FDE) identified using a patch test in a pediatric case associated with LEV
Background: Guidelines for management of patients with allergic conditions are available, but the added value of nurses, allied health care professionals (AHPs) and general practitioners (GPs), in the management of allergic disease has not been fully clarified. The European Academy of Allergy and Clinical Immunology (EAACI) appointed a task force to explore this issue. Aim: To investigate the added value of nurses, AHPs and GPs in management of allergic diseases, in an integrated model of care. Methods: A search was made of peer-reviewed literature published between 2010 and December 2020 (Cochrane Library, PubMed, and CINAHL) on the involvement of the various specific health care providers (HCPs) in the management of allergic diseases. Results: Facilitative models of care for patients with allergies can be achieved if HCP collaborate in the diagnosis and management. Working in multidisciplinary teams (MDT) can increase patients’ understanding of the disease, adherence to treatment, self-care capabilities, and ultimately improve quality of life. The MDT competencies and procedures can be improved and enhanced in a climate of mutual respect and shared values, and with inclusion of patients in the planning of care. Patient-centered communication among HCPs and emphasis on the added value of each profession can create an effective integrated model of care for patients with allergic diseases. Conclusion: Nurses, AHPs, and GPs, both individually and in collaboration, can contribute to the improvement of the management of patients with allergic disease. The interaction between the HCPs and the patients themselves can ensure maximum support for people with allergies.
We report for the first time the case of allergy to egusi seeds in an atopic child of Nigerian origin with allergy to other seeds and nuts. This case highlights the need to know and explore less common foods as potential allergens, the importance of modified skin prick testing and the basophil activation test to support the diagnosis of rare food allergies and of awareness about world cuisine and exotic foods as potential allergens.
Background: We tested the hypothesis that multiple obesity-related risk factors (obesity, physical activity, cardiopulmonary physical fitness, sleep-disorder breathing (SDB), and sleep quality) are associated with childhood asthma using a Mendelian randomization (MR) design. Furthermore, we aim to investigate whether these risk factors were associated with incident asthma prospectively. Methods: In total, 7069 children aged 12 from the Taiwan Children Health Study were enrolled in the current study. Cross-sectional logistic regression, one-sample MR, summary-level MR sensitivity analyses, and prospective survival analyses were used to investigate each causal pathway. Results: In MR analysis, three of the five risk factors (obesity, SDB, and sleep quality) were associated with asthma, with the highest effect sizes per interquartile range (IQR) increase observed for sleep quality (odds ratio [OR] =1.42; 95% confidence interval [CI]: 1.06 to 1.92) and the lowest for obesity (OR = 1.08; 95% CI: 1.00–1.16). In the prospective survival analysis, obesity showed the highest risk of incident asthma per IQR increase (hazard ratio [HR] = 1.28; 95% CI: 1.05 to 1.56), followed by SDB (HR = 1.18; 95% CI: 1.08 to 1.29) and sleep quality (HR = 1.10; 95% CI: 1.03 to 1.17). Conclusion: The most plausible risk factors for asthma were obesity, SDB, and poor sleep quality. For the prevention of childhood asthma, relevant stakeholders should prioritize improving children’s sleep quality and preventing obesity comorbidities such as SDB.
Eosinophilic pustular folliculitis (EPF) of infancy (EPFI), as a rare variant of EPF, is an inflammatory dermatosis characterized by recurrent outbreaks, itchy papulopustules and involvement of scalp and other body areas. In our case, we present a 3-month-old boy with persistent itchy vesiculopustular rashes on the scalp, hands and feet, eosinophilia in the peripheral blood test, widespread eosinophil clusters in the swab of the pustule and egg allergy in the skin prick test. This is the first case of EPFI associated with food allergy that is permanently suppressed by elimination diet with the limited use of cetirizine.
Background: Allergic rhinitis (AR) is the most common allergic disease in children and is closely associated with asthma in the context of atopic march. The development process of AR in early childhood, however, is not well understood due to the absence of definitive diagnostic criteria. We prospectively investigated the process in regard to not only the nasal symptoms and sensitization, but also the nasal cytology, in relation to asthma in a high-risk cohort. Methods: Infants under 2 years of age with atopic dermatitis (AD) and/or food allergy (FA) without a diagnosis of asthma were recruited and followed prospectively for 2 years. The phenotype of perennial AR was classified based on the presence/absence of 1) persistent nasal symptoms, 2) nasal eosinophils and 3) HDM sensitization, the most common allergen for perennial AR in Japan. AR-like phenotypes were defined as positive for at least 2 of those 3 categories. Results: A total of 304 children were enrolled, and 242 subjects (80%) completed the 2-year observation. The prevalence of eosinophilia in nasal secretions increased from 18.5% to 69.9%, while HDM-specific IgE >0.35 kUA/L increased from 30.6% to 74.8%. AR-like phenotypes increased from 18.4% to 65.0%. The cumulative incidence of physician-diagnosed asthma during the 2-year follow-up was significantly higher in the subjects with an AR-like phenotype at 1 year than in those with a non-AR phenotypes. Conclusions: The prevalence of an HDM-related AR-like phenotype was markedly increased during infancy in high-risk infants with AD/FA and was associated with asthma.
Background: Although well described in adults, there are scarce and heterogeneous data on the diagnosis and management of chronic urticaria (CU) in children (0-18 years) throughout Europe. Our aim was to explore country differences and identify the extent to which the EAACI/GA²LEN/EDF/WAO guideline recommendations for paediatric urticaria are implemented. Methods: The EAACI Taskforce for paediatric CU disseminated an online clinical survey among EAACI paediatric section members. Members were asked to answer 35 multiple choice questions on current practices in their respective centres. Results: The survey was sent to 2,773 physicians of whom 358 (13.8%) responded, mainly paediatric allergists (80%) and paediatricians (49.7%), working in 69 countries. For diagnosis, Southern European countries used significantly more routine tests (e.g., autoimmune testing, allergological tests, and parasitic investigation) than Northern European countries. Most respondents (60.3%) used a 2nd generation antihistamine as first- line treatment of whom 64.8% up dosed as a second- line. Omalizumab, was used as a second line treatment by 1.7% and third-line by 20.7% of respondents. Most clinicians (65%) follow EAACI/WAO/GA2LEN/EDF guidelines when diagnosing CU, and only 7.3% follow no specific guidelines. Some clinicians prefer to follow national guidelines (18.4%, mainly Northern European) or the AAAAI practice parameter (1.7%). Conclusions: Even though most members of the Paediatric Section of EAACI are familiar with the EAACI/WAO/GA2LEN/EDF guidelines, a significant number do not follow them. Also, the large variation in diagnosis and treatment strengthens the need to re-evaluate, update and standardize guidelines on the diagnosis and management of CU in children.
Potential protective effects of breast milk and amniotic fluid against novel coronavirus SARS-CoV-2.Authors: April Rees1, Stephen Turner2, Catherine Thornton1*1 Institute of Life Science, Swansea University Medical School, Swansea, Wales, UK, SA2 8PP2 University of Aberdeen, The Institute of Applied Health Sciences, Aberdeen, Scotland, UK AB24 3FXDisclosure: The authors report no conflict of interest.Funding: This work was supported by the EPSRC Impact Acceleration Account at Swansea University and the Welsh Government Sêr Cymru III Tackling COVID-19 initiative.*Corresponding author:Professor Cathy ThorntonILS1, Swansea University Medical SchoolSingleton CampusSwansea UniversitySwansea, Wales, UKSA2 8PPTelephone: 01792 602122Email: firstname.lastname@example.orgKeywords: Breast milk, amniotic fluid, SARS-CoV-2, neonateWord count: 769
Background: Primary immunodeficiency diseases (PIDs) comprise more than 400 rare diseases with potential life-threatening conditions. Clinical manifestations and genetic defects are heterogeneous and diverse among populations. Here, we aimed to characterize the clinical, immunological and genetic features of Thai pediatric patients with PIDs. The use of whole exome sequencing (WES) in diagnosis and clinical decision making was also assessed. Methods: 36 unrelated patients with clinical and laboratory findings consistent with PIDs were recruited from January 2010 to December 2020. WES was performed to identify the underlying genetic defects. Results: The median age of disease onset was 4 months (range; 1 month to 13 years) and 24 were male (66.7%). Recurrent sinopulmonary tract infection was the most common clinical presentation followed by septicemia, and severe pneumonia. Using WES, we successfully identified the underlying genetic defects in 18 patients (50%). Of the 20 variants identified, six have not been previously described (30%). According to the International Union of Immunological Societies (IUIS), 38.9% of these detected cases (7/18) were found to harbor variants associated with genes in combined immunodeficiencies with associated or syndromic features (Class II). Conclusion: The diagnostic yield of WES in this patient cohort was 50%. Six novel genetic variants in PID genes were identified. The clinical usefulness of WES in PIDs was demonstrated, emphasizing it as an effective diagnostic strategy in these genetically heterogeneous disorders.
Improved treatment adherence and allergic disease control during a COVID-19 pandemic lockdownPauline Poh Lin Chan Ng, MBBS, MRCPCH1,2, Alicia Yi Hui Kang, BSc1, Liang Shen, PhD3, Lydia Su-Yin Wong, MBBS, MRCPCH1,2, Elizabeth Huiwen Tham, MBBS, MCI, MRCPCH*1,2,41Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore (NUS), Singapore2Khoo Teck Puat-National University Children’s Medical Institute, National University Health System (NUHS), Singapore3Biostatistics Unit, Yong Loo Lin School of Medicine, National University of Singapore (NUS), Singapore4Human Potential Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
Background: The European Academy of Allergy and Clinical Immunology (EAACI) is in the process of updating the guidelines on the diagnosis and management of food allergy. The existing guidelines are based on a systematic review of the literature until 30th September 2012. Therefore, a new systematic review must be undertaken to inform the new guidelines. This systematic review aims to assess the accuracy of index tests to support the diagnosis of IgE-mediated food allergy. Methods: The databases Cochrane CENTRAL (Trials), MEDLINE (OVID) and Embase (OVID) will be searched for diagnostic test accuracy studies from 1st October 2012 to 30th June 2021. Inclusion and exclusion criteria will be used to select appropriate studies. Data from these studies will be extracted and tabulated, and then reviewed for risk of bias and applicability using the QUADAS-2 tool. All evaluation will be done in duplicate. Studies with a high risk of bias and low applicability will be excluded. Meta-analysis will be performed if there are three or more studies of the same index test and food. Results: A protocol for the systematic review and meta-analyses is presented and was registered using Prospero prior to commencing the literature search. Discussion: Oral food challenges are the reference standard for diagnosis but involve considerable risks and resources. This protocol for systematic review aims to assess the accuracy of various tests to diagnose food allergy, which can be useful in both clinical and research settings.
Title :Shrimp-Allergic Patients in a Multi-Food Oral Immunotherapy TrialAuthors :Diem-Tran I. Nguyen MD1, Sayantani B. Sindher MD2,3, R. Sharon Chinthrajah MD2,3, Kari Nadeau MD PhD2,3, Carla M. Davis MD1,41Department of Pediatrics, Baylor College of Medicine, Houston, TX, United States2Sean N. Parker Center for Allergy and Asthma Research, Stanford University, Palo Alto, CA, USA3Division of Pulmonary, Allergy and Critical Care Medicine, Dept of Medicine, Stanford, CA, USA.4Section of Immunology, Allergy and Retrovirology, Baylor College of Medicine and Texas Children’s Hospital, Houston, TX, United StatesCorresponding Author:Carla M. Daviscarlad@bcm.eduWord Count: 978To the Editor:Shellfish allergy is one of the most common food allergies in the United States accounting for approximately 25% of adulthood and 20% of childhood food allergies (FA).1,2Of the different types of shellfish, shrimp are considered the most allergenic. The prevalence of shellfish allergy in children is substantial at 1.3% and may result in a greater prevalence in the adult population (3%) given that shellfish allergies have a low rate of spontaneous resolution.2,3Shrimp allergy (SA) is a leading cause of severe food reactions and results in high rates of healthcare usage.4Nearly 50% of patients with SA experience at least one lifetime food allergy related Emergency Department visit, yet only 42% of adults and 61% of children with SA reported having a physician confirmed diagnosis.1,2The lack of physician confirmation of SA is concerning given the potentially life threatening consequences of accidental exposure.5Currently, there is no cure and the only management strategies are avoidance and treatment for severe reactions with epinephrine.6 However, avoidance can be difficult due to the high incidence of cross-contamination, requiring strict dietary limitations.Oral immunotherapy (OIT) has emerged as a promising treatment for FA. In OIT, patients ingest increasing doses of the allergenic food with the goal of achieving desensitization so that reactions are less severe. Once a maintenance dose is achieved, the allergen needs to be regularly ingested to preserve the desensitized state. Although OIT has been recently approved by the FDA for peanut allergies, there has been little data in shrimp allergic patients. In this case-series, we discuss a subset of three patients who received shrimp OIT as part of a phase II, multi-food, omalizumab-facilitated OIT clinical trial.Multi-food allergic patients were recruited to a multi-site clinical trial between January 1 and November 30, 2016. Full details of trial design, inclusion criteria, and exclusion criteria have been previously reported.7Patients initially underwent testing with skin prick testing (SPT), specific IgE testing, and double-blind placebo-controlled food challenge (DBPCFC) to confirm their allergy to their culprit foods. To be included, patients were required to have a positive SPT of> 6 mm wheal diameter, specific IgE> 0.35 kU/L, a total IgE <2,000 kU/L, and a clinical reaction with DBPCFCs at < 125 mg dose.Patients enrolled in this clinical trial received 0.016 mg/kg (IU/mL) omalizumab per month or 0.008 mg/kg (IU/mL) every two weeks (based on asthma dosing guidelines)7 from week 1-16. At week 8, multi-food OIT was started and escalated under an investigator-supervised multi-OIT up-dosing regimen to reach a maintenance dose of > 1g of each allergen. Participants who reached maintenance by week 28-29 were randomized and received week 30 DBPCFC to assess desensitization to the allergenic foods. Patients were then randomized to one of three arms: high dose maintenance (1000 mg), low dose maintenance (300 mg), or placebo (0 mg). This randomized dose was dispensed at the last week 30 DBPCFC and consumed until week 36. At week 36, DBPCFC was repeated to assess sustained unresponsiveness with differing daily doses of protein.A total of 70 patients were enrolled, with three found to have SA. Their demographic data and baseline characteristics are detailed in Table 1. All three patients also had asthma, allergic rhinitis, and atopic dermatitis. Each had a convincing clinical history, elevated total IgE, and positive SPT to a mixture of white, brown, and pink shrimp extract from Greer. The diagnosis was confirmed by a reaction during DBPCFC withLitopenaeus setiferus shrimp flour that was manufactured at a Good Manufacturing Practice facility at Stanford University.Clinical outcomes and adverse events are detailed in Table 2. All 3 patients tolerated dose escalation without serious adverse events or epinephrine requirement, were able to achieve maintenance dose, and did not have an allergic reaction at the Week 30 DBPCFC. Patient A was randomized to the placebo treatment arm while the other two patients were randomized to the 300 mg maintenance OIT arm. At Week 36, Patient A and Patient B had sustained unresponsiveness to 12,000 mg of shrimp extract. Patient C did not follow-up for assessment.It is encouraging that all 3 shrimp allergic patients in this multi-food OIT clinical trial were able to reach maintenance dose OIT (> 1g), and 2 out of 3 had no reaction with the 12g DBPCFC dose at Week 30. These results suggest that OIT is a potentially efficacious treatment for SA and warrants further study. There is little data on the optimal shrimp allergen product, dose escalation regimen, and adjunct therapies such as omalizumab to achieve desensitization.There are several known target allergens that contribute to SA. The first major allergen is tropomyosin, a heat-stable, actin-binding protein found in both muscle and non-muscle cells. Tropomyosin has been implicated as the source of significant cross-reactivity between species of mollusks, crustaceans, and non-shellfish such as cockroaches and mites.8,9Other shrimp allergens that have been identified include arginine kinase, myosin light chain, sarcoplasmic calcium-binding protein, hemocyanin, and troponin C.8,9 It is possible that patients with allergies to different shrimp components may have varied responses to OIT, and thus additional research is necessary to determine which patient subgroups are most likely to benefit from shrimp OIT.Our case series is limited by small sample size, with only three patients receiving shrimp OIT and two following up at week 36. Although all patients appeared to develop short-term tolerance by week 30, it is unclear how durable this response would be with long-term follow up. Furthermore, there are risks associated with OIT.SA is a common and serious food allergy that is underdiagnosed and often lifelong. There are currently no effective treatments other than strict avoidance, which can be difficult to achieve and lead to poor quality of life. Our case series presents initial evidence suggesting that shrimp OIT may be an effective strategy of addressing grave reactions faced by SA patients. Larger studies need to be performed to validate these findings.References :1. Gupta, R. S. et al.Prevalence and Severity of Food Allergies Among US Adults. JAMA Netw Open 2, e185630 (2019).2. Wang, H. T., Warren, C. M., Gupta, R. S. & Davis, C. M. Prevalence and Characteristics of Shellfish Allergy in the Pediatric Population of the United States. J. Allergy Clin. Immunol. Pract. 8, 1359–1370.e2 (2020).3. Zotova, V. et al.Low resolution rates of seafood allergy. J. Allergy Clin. Immunol. Pract. 7, 690–692 (2019).4. Ross, M. P. et al.Analysis of food-allergic and anaphylactic events in the National Electronic Injury Surveillance System. J. Allergy Clin. Immunol.121, 166–171 (2008).5. Tuano, K. T. S. et al. Improved diagnostic clarity in shrimp allergic non-dust-mite sensitized patients. Allergy Asthma Proc. 39, 377–383 (2018).6. Davis CM, Gupta RS, Aktas ON, Diaz V, Kamath SD, Lopata AL. Clinical Management of Seafood Allergy. J Allergy Clin Immunol Pract. 2020 Jan;8(1):37-44.7. Andorf, S. et al. A Phase 2 Randomized Controlled Multisite Study Using Omalizumab-facilitated Rapid Desensitization to Test Continued Discontinued Dosing in Multifood Allergic Individuals.EClinicalMedicine 7, 27–38 (2019).8. Faber, M. A. et al.Shellfish allergens: tropomyosin and beyond. Allergy 72, 842–848 (2017).9. Ruethers T, Taki AC, Johnston EB, Nugraha R, Le TTK, Kalic T, McLean TR, Kamath SD, Lopata AL. Seafood allergy: A comprehensive review of fish and shellfish allergens. Mol Immunol. 2018 Aug;100:28-57.
Transcriptome changes during peanut oral immunotherapy and omalizumab treatmentTo the Editor,Peanut allergy is a common food allergy and the main cause of anaphylaxis among children1. In recent years, oral immunotherapy has emerged as a promising treatment for children with different IgE-mediated food allergies, although safety issues must be considered2. The main aim of immunotherapy is to induce tolerance or desensitization to an allergen which otherwise causes an allergic reaction. For oral immunotherapy this means ingesting the allergen in a controlled manner with gradually increasing dosages. Specifically, peanut oral immunotherapy (pOIT) is able to induce tolerance/desensitization3. While the pathogenesis of food allergy in general is relatively well-studied4, mechanisms of OIT-induced tolerance are not well understood. Omalizumab (anti-IgE) used as treatment for severe allergic asthma and other IgE-driven allergies, can facilitate OIT initiation5, however, little is known about the involved mechanisms, including possible changes at the transcriptional level. We therefore investigated transcriptional changes in whole blood using RNA-sequencing profiles during omalizumab treatment and pOIT in participants from the FASTX (Food Allergen Suppression Therapy with Xolair ®) study previously described in detail elsewhere5.In brief, peanut-allergic adolescents (n=23 of whom 17 completed the study, age 12-18 years) were started on omalizumab (baseline) and treated for at least 8 weeks before starting pOIT (pOIT start) while on omalizumab. The peanut-dose was gradually increased during the 8 weeks until reaching a maintenance dose. Guided by a basophil activation test (BAT/CD-sens)6 after 8 weeks on the maintenance dose, participants decreased the omalizumab dose by 50% (maintenance) and continued to decrease the omalizumab dose if pOIT was tolerated. Eleven patients were able to tolerate pOIT without omalizumab protection for >8 weeks and then passed an open peanut food challenge (final); 6 patients could not discontinue omalizumab, but blood samples were obtained for analysis after 2-3 years of omalizumab treatment (final); 6 patients dropped out of the study. RNA-sequencing was performed on whole blood at baseline, pOIT start, maintenance and final time-points using the NovaSeq 6000 platform. DESeq2 was used for differential expression analysis of the omalizumab effect and a linear mixed-effect model for analyses during pOIT in combination with omalizumab (pOIT+O) after adjustment for treatment outcome and cell type. A complete description of the treatment protocol and method is given in Appendix S1.General characteristics of the study participants at baseline can be found in Table S1 . To elucidate if omalizumab treatment alone induced alterations in peripheral blood gene expression, we investigated the two first timepoints, baseline and pOIT start, however no significant differences were observed (Figure S1 ). In the longitudinal analysis (pOIT start to final), 680 genes associated with pOIT+O at nominal p <0.005 (Table S2 ). The Gene Ontology (GO) biological process of the up- and down-regulation of these 680 genes are presented in Figure 1A,B . Upregulation of 337 genes were linked to GO terms “protein regulation and modification”, while “neutrophil degranulation, immune response, phagocytosis, and metabolic process” were among the top terms for the downregulated 343 genes. Out of the 680 genes, 16 were differentially expressed at false discovery rate (FDR) adjusted p<0.05 (Table 1, Figure S2 ). The three genes with the largest negative and positive coefficients, respectively, are displayed in Figure 1C,D ; downregulation of ASGR2 ,GPBAR1 and HM13, and upregulation of USP44 ,ICOS and CDKN2AIP . Finally, we evaluated the enrichment of 680 pOIT+O-associated genes, relative to peripheral blood gene expression associated with acute peanut allergic reactions in a recently published clinical study by Watson et al using the same p-value cut-off (p<0.005)7. Out of our 680 significant genes, 108 genes overlapped with the differentially expressed genes in Watson et al7, mostly with opposite direction, Penrichment = 0.0095 (Figure 2 ).Our results demonstrate that omalizumab treatment alone does not induce alterations in whole blood gene expression in patients with severe food allergy. This is not surprising given that these patients were unexposed to peanut allergen at the time of blood sampling, and any concomitant asthma, rhinitis or eczema were well controlled. However, the longitudinal analysis during pOIT+O identified up- and downregulation of several immune-related genes. CD278/ICOS (Inducible T-cell costimulatory) is expressed on activated T-cells and appears to play a role in directing effector T-cell differentiation and responses during inflammatory conditions8. ICOS-expression on T regulatory cells and T follicular helper cells may be involved in the allergic disease mechanism9. In the pathway analyses, we observed significant enrichment for several GO biological process terms related to T-cell function and immune responses. Notably, we have previously described alterations in T-cell polyclonal in vitroactivation during pOIT +O in the FASTX study10. Comparing our findings with data described by Watson et al7 , suggests that pOIT+O may alter the expression level of many genes that were found activated during an acute peanut allergy reaction.The main limitations of this study are lack of any control subjects and small sample size. Moreover, further studies are needed to evaluate the long-term biological effect of pOIT+O.In conclusion, omalizumab treatment alone does not alter the transcriptional signature in peripheral blood of peanut allergic patients, but during pOIT+O, several immune-related signatures were observed. These results may provide insights into mechanisms of allergen tolerance.