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Altman MC, Segnitz RM, Larson D, et al., 2023, Nasal and blood transcriptomic pathways underpinning the clinical response to grass pollen immunotherapy, Journal of Allergy and Clinical Immunology, Vol: 152, Pages: 1247-1260, ISSN: 0091-6749
BACKGROUND: Allergen immunotherapy (AIT) is a well-established disease-modifying therapy for allergic rhinitis, yet the fundamental mechanisms underlying its clinical effect remain inadequately understood. OBJECTIVE: The GRASS study was a randomized, double-blind, placebo-controlled trial of timothy grass allergic individuals who received 2 years of placebo (n=30), subcutaneous (SCIT) (n=27), or sublingual immunotherapy (SLIT) (n=27) and were then followed for 1 additional year. Here we used yearly biospecimens from the GRASS study to identify molecular mechanisms of response. METHODS: We utilized longitudinal transcriptomic profiling of nasal brush and peripheral blood mononuclear cell (PBMC) samples after allergen provocation to uncover airway and systemic expression pathways mediating responsiveness to AIT. RESULTS: SCIT and SLIT demonstrated similar changes in gene module expression over time. In nasal samples, alterations included downregulation of pathways of mucus hypersecretion, leukocyte migration/activation, and endoplasmic reticulum stress (log2 fold changes (logFC) -0.133 to -0.640, FDRs <0.05). Interestingly, we observed upregulation of modules related to epithelial development, junction formation, and lipid metabolism (logFC 0.104 to 0.393, FDRs <0.05). In PBMCs, modules related to cellular stress response and type 2 cytokine signaling were reduced by immunotherapy (logFC -0.611 to -0.828, FDRs <0.05). Expression of these modules was also significantly associated with both Total Nasal Symptom Score and Peak Nasal Inspiratory Flow responses, indicating important links among treatment, module expression, and allergen response. CONCLUSION: Our results identify specific molecular responses of the nasal airway impacting barrier function, leukocyte migration activation, and mucus secretion, that are affected by both SCIT and SLIT, offering potential targets to guide novel strategies for AIT.
Shamji MH, Larson D, Eifan A, et al., 2021, Differential induction of allergen-specific IgA responses following timothy grass subcutaneous and sublingual immunotherapy, JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, Vol: 148, Pages: 1061-+, ISSN: 0091-6749
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Eifan A, Scadding G, Durham S, et al., 2021, Comparison of nasal allergen challenges with dissolved Timothy Grass pollen tablets and aqueous extract, Allergy, Vol: 76, Pages: 1543-1545, ISSN: 0105-4538
Sharif H, Acharya S, Dhondalay GKR, et al., 2021, Altered chromatin landscape in circulating T follicular helper and regulatory cells following grass pollen subcutaneous and sublingual immunotherapy, Journal of Allergy and Clinical Immunology, Vol: 147, Pages: 663-676, ISSN: 0091-6749
BACKGROUND: Allergen-specific immunotherapy (AIT) is a disease-modifying treatment that induces long-term T cell tolerance. OBJECTIVE: To evaluate the role of circulating CXCR5+PD-1+T follicular helper (cTFH) and T follicular regulatory (TFR) cells following grass pollen subcutaneous (SCIT) and sublingual (SLIT) immunotherapy and the accompanying changes in their chromatin landscape. METHODS: Phenotype and function of cTFH cells were initially evaluated in grass pollen-allergics (GPA, n= 28) and non-atopic controls (NAC, n=13) by mathematical algorithms developed to manage high-dimensional data and cell culture, respectively. cTFH and TFR cells were further enumerated in NAC (n=12), GPA (n=14), SCIT (n=10) and SLIT (n=8)-treated groups. Chromatin accessibility in cTFH and TFR cells was assessed by ATAC-seq to investigate epigenetic mechanisms underlying the differences between NAC, GPA, SCIT and SLIT. RESULTS: cTFH cells were shown to be distinct from TH2 and TH2A cell subsets, capable of secreting IL-4 and IL-21. Both cytokines synergistically promoted B cell class switching to IgE and plasma cell differentiation. Grass pollen allergen induced cTFH cell proliferation in GPA but not in NAC (P<.05). cTFH cells were higher in GPA compared to NAC and were lower in SCIT and SLIT (P<.01). Time-dependent induction of IL-4, IL-21 and IL-6 were observed in nasal mucosa following intranasal allergen challenge in GPA but not in SCIT and SLIT groups. TFR and IL-10+ cTFH cells were induced in SCIT and SLIT (all, P<.01). ATAC-seq analyses revealed differentially accessible chromatin regions in all groups. CONCLUSION: For the first time, we showed dysregulation of cTFH cells in GPA compared to NAC, SCIT and SLIT and induction of TFR and IL-10+ cTFH cells following SCIT and SLIT. Changes in the chromatin landscape were observed following AIT in cTFH and TFR cells.
Orban N, Jacobson MR, Nouri-Aria KT, et al., 2021, Repetitive nasal allergen challenge in allergic rhinitis: priming and Th2-type inflammation but no evidence of remodelling., Clinical and Experimental Allergy, Vol: 51, Pages: 329-338, ISSN: 0954-7894
BACKGROUND: Local tissue eosinophilia and Th2-cytokines are characteristic features of seasonal allergic rhinitis. Airway-remodelling is a feature of asthma whereas evidence for remodelling in allergic rhinitis (AR) is conflicting. OBJECTIVE: By use of a novel human repetitive nasal allergen challenge (RAC) model, we evaluated the relationship between allergic inflammation and features of remodelling in AR. METHODS: Twelve patients with moderate-severe AR underwent 5-alternate day challenges with diluent which after 4-weeks were followed by 5-alternate day challenges with grass pollen extract. Nasal symptoms, Th1/Th2 cytokines in nasal secretion and serum were evaluated. Nasal biopsies were taken 24 hours after the 1st and 5th challenges with diluent and with allergen. Sixteen healthy controls underwent a single challenge with diluent and with allergen. Using immunohistochemistry, epithelial and sub-mucosal inflammatory cells, and remodelling markers were evaluated by computed image analysis. RESULTS: There was an increase in early and late-phase symptoms after every allergen challenge compared to diluent (both p<0.05) with evidence of both clinical and immunological priming. Nasal tissue eosinophils and IL-5 in nasal secretion increased significantly after RAC compared to corresponding diluent challenges (p<0.01, p=0.01, respectively). There was a correlation between submucosal mast cells and the early-phase clinical response (r=0.79, p=0.007) and an association between epithelial eosinophils and IL-5 concentrations in nasal secretion (r=0.69, p=0.06) in allergic rhinitis. No differences were observed after RAC with regards to epithelial integrity, reticular basement membrane thickness, glandular area, expression of markers of activation of airway-remodelling including α-SMA, HSP-47, extracellular matrix (MMP7, 9 and TIMP-1), angiogenesis and lymphangiogenesis for AR compared to healthy controls. CONCLUSION: Novel repetitive nasal allergen challenge in
Alvaro-Lozano M, Akdis CA, Akdis M, et al., 2020, Allergen Immunotherapy in Children User’s Guide, Pediatric Allergy and Immunology, Vol: 31, Pages: 1-101, ISSN: 0905-6157
Allergen immunotherapy is a cornerstone in the treatment of allergic children. The clinical efficiency relies on a well-defined immunologic mechanism promoting regulatory T cells and downplaying the immune response induced by allergens. Clinical indications have been well documented for respiratory allergy in the presence of rhinitis and/or allergic asthma, to pollens and dust mites. Patients who have had an anaphylactic reaction to hymenoptera venom are also good candidates for allergen immunotherapy. Administration of allergen is currently mostly either by subcutaneous injections or by sublingual administration. Both methods have been extensively studied and have pros and cons. Specifically in children, the choice of the method of administration according to the patient's profile is important. Although allergen immunotherapy is widely used, there is a need for improvement. More particularly, biomarkers for prediction of the success of the treatments are needed. The strength and efficiency of the immune response may also be boosted by the use of better adjuvants. Finally, novel formulations might be more efficient and might improve the patient's adherence to the treatment. This user's guide reviews current knowledge and aims to provide clinical guidance to healthcare professionals taking care of children undergoing allergen immunotherapy.
Layhadi JA, Sharif H, Singh I, et al., 2019, Immunomodulatory properties of lolium perenne peptides for the treatment of seasonal allergic rhinitis, Congress of the European-Academy-of-Allergy-and-Clinical-Immunology (EAACI), Publisher: WILEY, Pages: 79-79, ISSN: 0105-4538
Shamji MH, Kappen J, Abubakar-Waziri H, et al., 2019, Nasal allergen neutralising IgG4 antibodies block IgE-mediated responses: novel biomarker of subcutaneous grass pollen immunotherapy, Journal of Allergy and Clinical Immunology, Vol: 143, Pages: 1067-1076, ISSN: 0091-6749
BACKGROUND: Grass pollen subcutaneous immunotherapy (SCIT) is associated with induction of serum IgG4-associated inhibitory antibodies that prevent IgE-facilitated allergen binding to B cells. OBJECTIVE: To determine whether SCIT induces nasal allergen-specific IgG4 antibodies with inhibitory activity that correlate closely with clinical response. METHODS: In a cross-sectional, controlled study, nasal fluid and sera were collected during the grass pollen season from 10 SCIT-treated patients, 13 untreated allergics (SAR) and 12 non-atopic controls (NA). Nasal and serum IgE and IgG4 to Phleum pratense (Phl p) components were measured by ISAC microarray. Inhibitory activity was measured by IgE-FAB assay. IL-10+Breg cells were quantified in peripheral blood by flow cytometry. RESULTS: Nasal and serum Phl p1 and Phl p5-specific IgE levels were elevated in SAR compared to NA (all, P < .001) and SCIT group. Nasal IgG4 levels were increased in SCIT compared to SAR group (P < .001) during the pollen season compared to out of season. IgG-associated inhibitory activity in nasal fluid and serum was significantly increased in SCIT compared to SAR group (both, P < .001). The magnitude of the inhibitory activity was 96% in the nasal fluid compared to 66% in serum and was reversed following depletion of IgG in nasal fluid (P = .03) and serum (P = .002). Both nasal fluid (r = -0.67, P = .0011) and serum (r = -0.59, P = .0097) blocking activity correlated global symptom improvement. IL-10+Breg cells were increased in season compared to out of season in SCIT group (P < .01). CONCLUSION: For the first time, we show that nasal IgG4-associated inhibitory activity correlate closely with the clinical response to allergen immunotherapy in allergic rhinitis with/without asthma.
Penagos M, Eifan AO, Durham SR, et al., 2018, Duration of allergen immunotherapy for long-term efficacy in allergic rhinoconjunctivitis, Current Treatment Options in Allergy, Vol: 5, Pages: 275-290, ISSN: 2196-3053
RationaleSubcutaneous and sublingual immunotherapy are effective for allergic rhinitis. An important question is whether allergen immunotherapy provides a sustained clinical effect after treatment cessation. In view of potential side effects, cost and the necessary patient commitment, long-term benefit is an important consideration for the recommendation of immunotherapy over standard pharmacotherapy.Purpose of reviewIn this review, we analyse the existing evidence for long-term effects of both routes of administration in the context of double-blind, placebo-controlled, randomised clinical trials that included a follow-up phase of at least 1 year after treatment cessation.Recent findingsOverall, evidence suggests that 3 years of either subcutaneous or sublingual immunotherapy result in clinical benefit and immunological changes consistent with allergen-specific tolerance sustained for at least 2–3 years after treatment cessation.SummaryThe data presented here support recommendations in international guidelines that both routes of administration should be continued for a minimum of 3 years. Gaps in the evidence remain regarding the long-term efficacy of immunotherapy for perennial rhinitis and studies performed in children.
Eifan A, Scadding G, Calderon M, et al., 2017, Relationship between response to grass pollen nasal allergen challenge and seasonal symptoms and the effect of treatment compliance, Annual Meeting of the British-Society-for-Allergy-and-Clinical-Immunology (BSACI), Publisher: WILEY, Pages: 1686-1687, ISSN: 0954-7894
Eifan AO, Orban N, Hwang W, et al., 2017, Increased expression of SMAD7 in persistent allergic rhinitis, Congress of the European-Academy-of-Allergy-and-Clinical-Immunology, Publisher: WILEY, Pages: 85-85, ISSN: 0105-4538
Scadding GW, Calderon MA, Shamji MH, et al., 2017, Effect of 2 years of treatment with sublingual grass pollen immunotherapy on nasal response to allergen challenge at three years among patients with moderate to severe seasonal allergic rhinitis: The GRASS randomized clinical trial, Journal of the American Medical Association, Vol: 317, Pages: 615-625, ISSN: 0098-7484
Importance Sublingual immunotherapy and subcutaneous immunotherapy are effective in seasonal allergic rhinitis. Three years of continuous treatment with subcutaneous immunotherapy and sublingual immunotherapy has been shown to improve symptoms for at least 2 years following discontinuation of treatment.Objective To assess whether 2 years of treatment with grass pollen sublingual immunotherapy, compared with placebo, provides improved nasal response to allergen challenge at 3-year follow-up.Design, Setting, and Participants A randomized double-blind, placebo-controlled, 3–parallel-group study performed in a single academic center, Imperial College London, of adult patients with moderate to severe seasonal allergic rhinitis (interfering with usual daily activities or sleep). First enrollment was March 2011, last follow-up was February 2015.Interventions Thirty-six participants received 2 years of sublingual immunotherapy (daily tablets containing 15 µg of major allergen Phleum p 5 and monthly placebo injections), 36 received subcutaneous immunotherapy (monthly injections containing 20 µg of Phleum p 5 and daily placebo tablets) and 34 received matched double-placebo. Nasal allergen challenge was performed before treatment, at 1 and 2 years of treatment, and at 3 years (1 year after treatment discontinuation).Main Outcomes and Measures Total nasal symptom scores (TNSS; range; 0 [best] to 12 [worst]) were recorded between 0 and 10 hours after challenge. The minimum clinically important difference for change in TNSS within an individual is 1.08. The primary outcome was TNSS comparing sublingual immunotherapy vs placebo at year 3. Subcutaneous immunotherapy was included as a positive control. The study was not powered to compare sublingual immunotherapy with subcutaneous immunotherapy.Results Among 106 randomized participants (mean age, 33.5 years; 34 women [32.1%]), 92 completed the study at 3 years. In the intent-to-treat population, mean TNSS sc
Scadding G, Eifan AO, Calderon MA, et al., 2017, Response to Nasal Challenge Correlates with Seasonal Outcomes during Grass Pollen Immunotherapy with Either Subcutaneous or Sublingual Immunotherapy, Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology (AAAAI), Publisher: MOSBY-ELSEVIER, Pages: AB385-AB385, ISSN: 0091-6749
Calderon M, Scadding G, Dumitru F, et al., 2016, Subcutaneous and sublingual grass pollen immunotherapy both reduce seasonal rhinitis symptoms and improve quality of life - a randomised, controlled trial, Annual Meeting of the British-Society-for-Allergy-and-Clinical-Immunology (BSACI), Publisher: WILEY-BLACKWELL, Pages: 1625-1625, ISSN: 0954-7894
Scadding G, Calderon M, Shamji M, et al., 2016, Grass pollen subcutaneous and sublingual immunotherapy inhibit allergen-induced nasal and skin responses: a randomised controlled trial, Annual Meeting of the British-Society-for-Allergy-and-Clinical-Immunology (BSACI), Publisher: WILEY-BLACKWELL, Pages: 1639-1640, ISSN: 0954-7894
Eifan AO, Durham SR, 2016, Pathogenesis of Rhinitis, Clinical and Experimental Allergy, Vol: 46, Pages: 1139-1151, ISSN: 1365-2222
Rhinitis is a heterogeneous condition that has been associated with inflammatory responses asin allergic rhinitis but can also occur in the absence of inflammation such as in so-called‘idiopathic’ (previously ‘vasomotor’) rhinitis. Allergic rhinitis affects approximately 1 in 4 ofthe population of westernised countries and is characterized by typical symptoms of nasalitching, sneezing, watery discharge and congestion. The intention of this review is toillustrate key concepts of the pathogenesis of rhinitis. Imbalance in innate and adaptiveimmunity together with environmental factors is likely to play major roles. In allergic rhinitis,initial allergen exposure and sensitization involves antigen presenting cells, T and Blymphocytes and results in the generation of allergen-specific T cells and allergen specificIgE antibodies. On re-exposure to relevant allergens crosslinking of IgE on mast cells resultsin the release of mediators of hypersensitivity such as histamine and immediate nasalsymptoms. Within hours, there is an infiltration by inflammatory cells, particularly Th2 Tlymphocytes, eosinophils and basophils into nasal mucosal tissue that results in the late-phaseallergic response. Evidence for nasal priming and whether or not remodelling may be afeature of allergic rhinitis will be reviewed. The occurrence of so-called ‘local’ allergicrhinitis in the absence of systemic IgE will be discussed. Non-allergic (non-IgE mediated)rhinitis will be considered in the context of inflammatory and non-inflammatory disorders.
Scadding G, Calderon M, Shamji MH, et al., 2016, Grass pollen subcutaneous and sublingual immunotherapy inhibit allergen-induced nasal responses and local Th2 cytokines: a randomised controlled trial, Meeting of the European-Academy-of-Allergy-and-Clinical-Immunology, Publisher: WILEY-BLACKWELL, Pages: 3-3, ISSN: 0105-4538
Orban N, Eifan A, Jacobson M, et al., 2016, A optimum human repetitive allergen challenge model of allergic rhinitis faithfully replicates seasonal Th2 mediated allergic inflammation, Meeting of the European-Academy-of-Allergy-and-Clinical-Immunology, Publisher: WILEY-BLACKWELL, Pages: 108-108, ISSN: 0105-4538
Steveling-Klein EH, Lao-Araya M, Koulias C, et al., 2016, A randomised placebo-controlled trial of sublingual immunotherapy tablet for seasonal rhinitis to grass allergen: clinical outcomes, local symptoms and early time course of immunologic changes, Meeting of the European-Academy-of-Allergy-and-Clinical-Immunology, Publisher: WILEY-BLACKWELL, Pages: 616-616, ISSN: 0105-4538
Scadding G, Calderon M, Shamji M, et al., 2016, Grass pollen subcutaneous immunotherapy results in faster and greater suppression of allergen-induced skin responses compared to sublingual immunotherapy: a randomised controlled trial, Meeting of the European-Academy-of-Allergy-and-Clinical-Immunology, Publisher: WILEY-BLACKWELL, Pages: 172-172, ISSN: 0105-4538
Steveling EH, Lao-Araya M, Koulias C, et al., 2016, Randomised Placebo-Controlled Trial of Grass Pollen Allergen Tablet Immunotherapy for Seasonal Rhinitis: Clinical and Surrogate Outcomes and Early Time Course of Immunologic Changes, Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology (AAAAI), Publisher: MOSBY-ELSEVIER, Pages: AB197-AB197, ISSN: 0091-6749
Orban N, Eifan A, Jacobson M, et al., 2016, Altered TGF-(I)over-cap<SUP>2</SUP> Signalling in Inflammatory Nasal Polyps Drive Remodelling in Crswnp, Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology (AAAAI), Publisher: MOSBY-ELSEVIER, Pages: AB402-AB402, ISSN: 0091-6749
Karakoc-Aydiner E, Eifan AO, Baris S, et al., 2016, Long-Term Effect of Sublingual and Subcutaneous Immunotherapy in Dust Mite-Allergic Children With Asthma/Rhinitis: A 3-Year Prospective Randomized Controlled Trial (vol 25, pg 334, 2015), JOURNAL OF INVESTIGATIONAL ALLERGOLOGY AND CLINICAL IMMUNOLOGY, Vol: 26, Pages: 144-144, ISSN: 1018-9068
Steveling EH, Lao-Araya M, Koulias C, et al., 2015, Protocol for a randomised, double-blind, placebo-controlled study of grass allergen immunotherapy tablet for seasonal allergic rhinitis: time course of nasal, cutaneous and immunological outcomes, Clinical and Translational Allergy, Vol: 5, ISSN: 2045-7022
BACKGROUND: Seasonal Allergic Rhinitis is characterised by inflammation of the nasal mucosa upon exposure to common aeroallergens, affecting up to 20-25 % of the population. For those patients whose symptoms are not controlled by standard medical treatment, allergen specific immunotherapy is a therapeutic alternative. Although several studies have shown changes in immunologic responses as well as long term tolerance following treatment with a sublingual allergy immunotherapy tablet, a detailed time course of the early mechanistic changes of local and systemic T and B cell responses and the effects on B cell repertoire in the nasal mucosa have not been fully examined. METHODS/DESIGN: This is a randomized, double-blind, single-centre, placebo controlled, two arm time course study based in the United Kingdom comparing sublingual allergy immunotherapy tablet (GRAZAX(®), ALK-Abello Horsholm, Denmark) plus standard treatment with placebo plus standard treatment. Up to 50 moderate to severe grass pollen allergic participants will be enrolled to ensure randomisation of at least 44. Further, we shall enrol 20 non-atopic volunteers. Screening will be completed before eligible atopic participants are randomised to one of the two treatment arms in a 1 to 1 ratio. The primary endpoint will be the total nasal symptom score assessed over 60 min following grass pollen nasal allergen challenge after 12 months of treatment. Clinical assessments and/or mechanistic analyses on blood, nasal fluid, brushing and biopsies will be performed at baseline at 1, 2, 3, 4 (coinciding with the peak pollen season), 6 and 12 months of treatment. After 12 months of treatment, unblinding will take place. Those atopic participants receiving active treatment will continue therapy for another 12 months followed by a post treatment phase of 12 months. Assessments and collection of biologic samples from these participants will take place again at 24 and at 36 mon
Eifan AO, Orban NT, Jacobson MR, et al., 2015, Severe Persistent Allergic Rhinitis Inflammation but No Histologic Features of Structural Upper Airway Remodeling, American Journal of Respiratory and Critical Care Medicine, Vol: 192, Pages: 1431-1439, ISSN: 1535-4970
Rationale: Increases in airway smooth muscle, extracellular matrix, and vascularity are prominent features of airway remodeling in asthma, whereas the extent of such remodeling in patients with persistent allergic rhinitis (PAR) is unknown.Objectives: To test the hypothesis that upper airway remodeling is a feature of PAR.Methods: Total nasal symptoms scores, nasal biopsies, and Th1 and Th2 cytokines from nasal lavage were assessed in subjects with severe PAR (n = 46) and healthy control subjects (n = 19). Angiolymphangiogenesis was examined using immunohistochemistry staining against CD31 (vascular endothelial cells), vascular endothelial growth factor-A, and D2-40 (lymphatic endothelial cells). Collagen and extracellular matrix proteins, such as heat shock protein-47 (markers of collagen synthesis), matrix metalloproteinase-9, and tissue inhibitor metalloproteinase-1, and α-smooth muscle actin (myofibroblasts) were evaluated as markers of activation of upper airway remodeling using image analysis, together with reticular basement membrane thickness, mucus gland area, collagen area, and submucosal effector inflammatory cells.Measurements and Main Results: Total nasal symptoms scores, visual analog scale, and total quality of life were significantly higher in PAR compared with healthy control subjects (P < 0.0001). Nasal lavage cytokine levels of IL-4 (P < 0.01), IL-5, and IL-13 (P < 0.001, respectively) were significantly higher in PAR compared with healthy control subjects. In addition there was an increase in submucosal eosinophils (P = 0.06). No statistical difference in terms of angiogenesis, lymphangiogenesis, deposition of extracellular matrix, collagen markers, reticular basement membrane thickness, or glandular percentage area was observed between PAR and healthy control subjects.Conclusions: Our data suggest that tissue remodeling is not a feature of PAR and
Eifan A, Jacobson M, Orban N, et al., 2015, Transforming growth factor-β may regulate allergic inflammation in allergic rhinitis but not remodeling, Annual Meeting of the British-Society-for-Allergy-and-Clinical-Immunology, Publisher: WILEY-BLACKWELL, Pages: 1896-1896, ISSN: 0954-7894
Eifan AO, Orban NT, Jacobson MR, et al., 2015, Decreased expression of nasal tissue TGF-beta may contribute to allergic inflammation in allergic rhinitis but not remodeling, Congress of the European-Academy-of-Allergy-and-Clinical-Immunology, Publisher: WILEY-BLACKWELL, Pages: 628-628, ISSN: 0105-4538
Eifan A, 2015, In Memory of My Mentor Professor Isil Barlan, TURKISH JOURNAL OF IMMUNOLOGY, Vol: 3, Pages: 46-46, ISSN: 1301-109X
Scadding GW, Eifan AO, Lao-Araya M, et al., 2015, Effect of grass pollen immunotherapy on clinical and local immune response to nasal allergen challenge, ALLERGY, Vol: 70, Pages: 689-696, ISSN: 0105-4538
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Scadding GW, Eifan A, Penagos M, et al., 2015, Local and systemic effects of cat allergen nasal provocation, Clinical and Experimental Allergy, Vol: 45, Pages: 613-623, ISSN: 0954-7894
BackgroundCat allergen is widely distributed in homes and schools; allergic sensitization is common.ObjectiveTo develop a model of cat allergen nasal challenge to establish dose–response and time–course characteristics and investigate local and systemic biomarkers of allergic inflammation.MethodsNineteen cat‐allergic individuals underwent titrated nasal challenge, range 0.243 to 14.6 μg/mL Fel d1, and matched diluent‐only provocation. Clinical response to 8 h was assessed by symptom scores and peak nasal inspiratory flow (PNIF). Nasal fluid was collected using polyurethane sponges and analysed by ImmunoCAP and multiplex assays. Whole blood flow cytometry for basophil surface CD63, CD107a, and CD203c was carried out at baseline and 6 h post‐challenge.ResultsA dose–response to allergen was seen in symptom scores and PNIF, maximal at 10 000 BU/mL (4.87 μg/mL Fel d1), P < 0.0001 vs. diluent. Nasal fluid tryptase was elevated at 5 min after challenge (P < 0.05 vs. diluent); eotaxin, IL‐4, ‐5, ‐9, and ‐13 were increased at 8 h (P < 0.05 to P < 0.0001 vs. diluent); TSLP was undetectable; IL‐10, IL‐17A, and IL‐33 were unchanged compared to diluent challenge. Nasal fluid IL‐5 and IL‐13 correlated inversely with PNIF after challenge (IL‐5, r = −0.79, P < 0.0001; IL‐13, r = −0.60, P = 0.006). Surface expression of CD63 and CD107a was greater at 6 h than at baseline, both in the presence (both P < 0.05) and absence (CD63, P < 0.01; CD107a, P < 0.05) of in vitro allergen stimulation; no changes were seen on diluent challenge day.ConclusionsCat allergen nasal challenge produces local and systemic Th2‐driven inflammatory responses and has potential as a surrogate outcome measure in clinical trials.
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