Publications
803 results found
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
Garcia RM, Belgrave D, Clark A, et al., 2016, Cardiac haemodynamic changes during acute IgE-mediated peanut allergic reactions in man, Meeting of the European-Academy-of-Allergy-and-Clinical-Immunology, Publisher: WILEY-BLACKWELL, Pages: 287-288, ISSN: 0105-4538
Bousquet J, Farrell J, Crooks G, et al., 2016, Scaling up strategies of the chronic respiratory disease programme of the European Innovation Partnership on Active and Healthy Ageing (Action Plan B3: Area 5)., Clinical and Translational Allergy, Vol: 6, ISSN: 2045-7022
Action Plan B3 of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) focuses on the integrated care of chronic diseases. Area 5 (Care Pathways) was initiated using chronic respiratory diseases as a model. The chronic respiratory disease action plan includes (1) AIRWAYS integrated care pathways (ICPs), (2) the joint initiative between the Reference site MACVIA-LR (Contre les MAladies Chroniques pour un VIeillissement Actif) and ARIA (Allergic Rhinitis and its Impact on Asthma), (3) Commitments for Action to the European Innovation Partnership on Active and Healthy Ageing and the AIRWAYS ICPs network. It is deployed in collaboration with the World Health Organization Global Alliance against Chronic Respiratory Diseases (GARD). The European Innovation Partnership on Active and Healthy Ageing has proposed a 5-step framework for developing an individual scaling up strategy: (1) what to scale up: (1-a) databases of good practices, (1-b) assessment of viability of the scaling up of good practices, (1-c) classification of good practices for local replication and (2) how to scale up: (2-a) facilitating partnerships for scaling up, (2-b) implementation of key success factors and lessons learnt, including emerging technologies for individualised and predictive medicine. This strategy has already been applied to the chronic respiratory disease action plan of the European Innovation Partnership on Active and Healthy Ageing.
Durham SR, Creticos PS, Nelson HS, et al., 2016, Treatment effect of sublingual immunotherapy tablets and pharmacotherapies for seasonal and perennial allergic rhinitis: Pooled analyses, Journal of Allergy and Clinical Immunology, Vol: 138, Pages: 1081-1088.e4, ISSN: 1097-6825
BACKGROUND: Data comparing the treatment effect of allergy immunotherapy and pharmacotherapy are lacking. OBJECTIVE: We sought to indirectly compare the treatment effect of sublingual immunotherapy (SLIT)-tablets with pharmacotherapy for seasonal allergic rhinitis (SAR) and perennial allergic rhinitis (PAR). METHODS: Pooled data from randomized, double-blind, placebo-controlled trials for the clinical development programs of selected allergic rhinitis treatments were evaluated. Total nasal symptom scores (TNSSs) relative to placebo were compared. Subjects scored symptoms daily during entire pollen seasons in 6 timothy grass SLIT-tablet trials (n = 3094) and 2 ragweed SLIT-tablet trials (n = 658) and during the last 8 weeks of treatment in 2 house dust mite (HDM) SLIT-tablet trials (n = 1768). Subjects scored symptoms daily in 7 montelukast (10 mg, n = 6799), 9 desloratadine (5 mg, n = 4455), and 8 mometasone furoate nasal spray (MFNS; 200 μg daily, n = 2140) SAR or PAR trials. SLIT-tablet trials allowed rescue medication use, whereas most pharmacotherapy trials did not. A fixed-effect meta-analysis method estimated differences in on-treatment average TNSSs. RESULTS: In grass and ragweed SLIT-tablet trials, overall improvement in TNSSs relative to placebo was 16.3% and 17.1%, respectively. In HDM SLIT-tablet trials, TNSS overall improvement relative to placebo was 16.1%. In the montelukast, desloratadine, and MFNS trials, TNSS overall improvement relative to placebo was 5.4%, 8.5%, and 22.2%, respectively, for SAR trials, and 3.7%, 4.8%, and 11.2%, respectively, for PAR trials. CONCLUSIONS: Although comparisons were limited by study design heterogeneity and use of rescue medications in SLIT-tablet trials, effects on nasal symptoms with timothy grass and ragweed SLIT-tablets were nearly as great as with MFNS and numerically greater than with montelukast and desloratadine for SAR. H
Tam HH, Calderon MA, Manikam L, et al., 2016, Specific allergen immunotherapy for the treatment of atopic eczema: a Cochrane systematic review, ALLERGY, Vol: 71, Pages: 1345-1356, ISSN: 0105-4538
Varricchi G, Harker J, Borriello F, et al., 2016, T follicular helper (Tfh ) cells in normal immune responses and in allergic disorders., Allergy, Vol: 71, Pages: 1086-1094, ISSN: 0105-4538
Follicular helper T cells (Tfh ) are located within germinal centers of lymph nodes. Cognate interaction between Tfh , B cells, and IL-21 drives B cells to proliferate and differentiate into plasma cells thereby leading to antibody production. Tfh cells and IL-21 are involved in infectious and autoimmune diseases, immunodeficiencies, vaccination, and cancer. Human peripheral blood CXCR5(+) CD4(+) T cells comprise different subsets of Tfh -like cells. Despite the importance of the IgE response in the pathogenesis of allergic disorders, little is known about the role of follicular and blood Tfh cells and IL-21 in human and experimental allergic disease. Here, we review recent advances regarding the phenotypic and functional characteristics of both follicular and blood Tfh cells and of the IL-21/IL-21R system in the context of allergic disorders.
Tam H, Calderon MA, Manikam L, et al., 2016, Specific allergen immunotherapy for the treatment of atopic eczema: a systematic review, Allergy, Vol: 71, Pages: 1345-1356, ISSN: 0105-4538
Background: Specific allergen immunotherapy (SIT) is an effective allergy treatment, but it is unclear whether SIT is effective for atopic eczema (AE). We undertook a systematic review to assess SIT efficacy and safety for treating AE.Methods: We searched databases, ongoing clinical trials registers, and conference proceedings up to July 2015. Randomised-controlled trials (RCTs) of SIT using standardised allergen extracts, compared with placebo/control for treating AE in patients with allergic sensitisation were eligible. Results: We identified 12 eligible trials with 733 participants. Interventions included subcutaneous (6 trials), sublingual (4 trials), oral, or intradermal SIT in children/adults allergic to house dust mite (10 trials), grass pollen or other inhalants. Risk of bias was moderate, with high loss to follow-up and non-blinding as the main concerns. For our primary outcomes three studies (208 participants) reported no significant difference - patient-reported global disease severity improvement RR 0.75 (95%CI 0.45, 1.26); eczema symptoms mean difference -0.74 on a 20-point scale (95%CI -1.98, 0.50). Two studies (85 participants) reported a significant difference - SIT improved global disease severity RR 2.85 (95%CI 1.02, 7.96); and itch mean difference -4.20 on a 10-point scale (95%CI -3.69, -4.71). Meta-analysis was limited due to extreme statistical heterogeneity. For some secondary outcomes, meta-analyses showed benefits for SIT eg investigator-rated improvement in eczema severity RR 1.48 (95%CI 1.16, 1.88; 6 trials, 262 participants). We found no evidence of adverse effects. The overall quality of evidence was low.
Bousquet J, Schünemann HJ, Hellings PW, et al., 2016, MACVIA clinical decision algorithm in adolescents and adults with allergic rhinitis, Journal of Allergy and Clinical Immunology, Vol: 138, Pages: 367-374.e2, ISSN: 1097-6825
The selection of pharmacotherapy for patients with allergic rhinitis (AR) depends on several factors, including age, prominent symptoms, symptom severity, control of AR, patient preferences, and cost. Allergen exposure and the resulting symptoms vary, and treatment adjustment is required. Clinical decision support systems (CDSSs) might be beneficial for the assessment of disease control. CDSSs should be based on the best evidence and algorithms to aid patients and health care professionals to jointly determine treatment and its step-up or step-down strategy depending on AR control. Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon (MACVIA-LR [fighting chronic diseases for active and healthy ageing]), one of the reference sites of the European Innovation Partnership on Active and Healthy Ageing, has initiated an allergy sentinel network (the MACVIA-ARIA Sentinel Network). A CDSS is currently being developed to optimize AR control. An algorithm developed by consensus is presented in this article. This algorithm should be confirmed by appropriate trials.
Dhami S, Nurmatov U, Roberts G, et al., 2016, Allergen immunotherapy for allergic rhinoconjunctivitis: protocol for a systematic review., Clinical and Translational Allergy, Vol: 6, ISSN: 2045-7022
BACKGROUND: The European Academy of Allergy and Clinical Immunology (EAACI) is in the process of developing the EAACI Guidelines for Allergen Immunotherapy (AIT) for the Management of Allergic Rhinoconjunctivitis. We seek to critically assess the effectiveness, cost-effectiveness and safety of AIT in the management of allergic rhinoconjunctivitis. METHODS: We will undertake a systematic review, which will involve searching international biomedical databases for published, in progress and unpublished evidence. Studies will be independently screened against pre-defined eligibility criteria and critically appraised using established instruments. Data will be descriptively and, if possible and appropriate, quantitatively synthesised. CONCLUSION: The findings from this review will be used to inform the development of recommendations for EAACI's Guidelines on AIT.
Tam H, Calderon MA, Manikam L, et al., 2016, Specific allergen immunotherapy for the treatment of atopic eczema., Cochrane Database of Systematic Reviews, Vol: 2, ISSN: 1469-493X
BACKGROUND: Specific allergen immunotherapy (SIT) is a treatment that may improve disease severity in people with atopic eczema (AE) by inducing immune tolerance to the relevant allergen. A high quality systematic review has not previously assessed the efficacy and safety of this treatment. OBJECTIVES: To assess the effects of specific allergen immunotherapy (SIT), including subcutaneous, sublingual, intradermal, and oral routes, compared with placebo or a standard treatment in people with atopic eczema. SEARCH METHODS: We searched the following databases up to July 2015: the Cochrane Skin Group Specialised Register, CENTRAL in the Cochrane Library (Issue 7, 2015), MEDLINE (from 1946), EMBASE (from 1974), LILACS (from 1982), Web of Science™ (from 2005), the Global Resource of EczemA Trials (GREAT database), and five trials databases. We searched abstracts from recent European and North American allergy meetings and checked the references of included studies and review articles for further references to relevant trials. SELECTION CRITERIA: Randomised controlled trials (RCTs) of specific allergen immunotherapy that used standardised allergen extracts in people with AE. DATA COLLECTION AND ANALYSIS: Two authors independently undertook study selection, data extraction (including adverse effects), assessment of risk of bias, and analyses. We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We identified 12 RCTs for inclusion in this review; the total number of participants was 733. The interventions included SIT in children and adults allergic to either house dust mite (10 trials), grass pollen, or other inhalant allergens (two trials). They were administered subcutaneously (six trials), sublingually (four trials), orally, or intradermally (two trials). Overall, the risk of bias was moderate, with high loss to follow up and lack of blinding as the main methodological concern.Our primary outcomes were 'Participant- or parent-reported globa
Durham SR, Penagos M, 2016, Sublingual or subcutaneous immunotherapy for allergic rhinitis?, JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, Vol: 137, Pages: 339-+, ISSN: 0091-6749
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- Citations: 136
Slovick AD, Douiri A, Muir R, et al., 2016, A Randomized Placebo-Controlled Trial of Intradermal Grass Pollen Immunotherapy for Seasonal Allergic Rhinitis, Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology (AAAAI), Publisher: MOSBY-ELSEVIER, Pages: AB94-AB94, 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
Allekotte S, Shamji MH, Zadoyan GV, et al., 2016, Facilitated Allergen Binding (FAB) Is a Meaningful Immunological Biomarker for Monitoring Immediate Clinical Efficacy in Short-Term Peptide Allergen Immunotherapy, Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology (AAAAI), Publisher: MOSBY-ELSEVIER, Pages: AB403-AB403, ISSN: 0091-6749
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Sharif HHHA, Parkin R, Ito C, et al., 2016, Immune Tolerance Induction Following AIT Is Associated with Induction of Circulating CD4+CXCR5+PD-1+FoxP3+T Follicular Regulatory Cells, Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology (AAAAI), Publisher: MOSBY-ELSEVIER, Pages: AB97-AB97, ISSN: 0091-6749
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
Ntavli E, Turner PJ, Boyle RJ, et al., 2016, Group 2 Innate Lymphoid Cells: New Players in Peanut Allergy, Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology (AAAAI), Publisher: MOSBY-ELSEVIER, Pages: AB74-AB74, ISSN: 0091-6749
Mohseni YR, Turner PJ, Boyle RJ, et al., 2016, Intracellular Expression of Fluorochrome Labelled-Diamine Oxidase in Basophils: A Novel Diagnostic Tool for Peanut Allergy, Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology (AAAAI), Publisher: MOSBY-ELSEVIER, Pages: AB137-AB137, ISSN: 0091-6749
Ruiz-Garcia M, Hayward C, Tang A, et al., 2016, Effects of Intramuscular Epinephrine on Cardiovascular Parameters during IgE-Mediated Allergic Reactions to Peanut, Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology (AAAAI), Publisher: MOSBY-ELSEVIER, Pages: AB50-AB50, ISSN: 0091-6749
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Chaker AM, Shamji MH, Dumitru FA, et al., 2016, Short-term subcutaneous grass pollen immunotherapy under the umbrella of anti-IL-4: A randomized controlled trial, JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, Vol: 137, Pages: 452-+, ISSN: 0091-6749
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- Citations: 41
Froidure A, Mouthuy J, Durham SR, et al., 2016, Asthma phenotypes and IgE responses, European Respiratory Journal, Vol: 47, Pages: 304-319, ISSN: 1399-3003
The discovery of IgE represented a major breakthrough in allergy and asthma research, whereas the clinical interest given to IgE in asthma has been blurred until the arrival of anti-IgE biotherapy. Novel facets of the complex link between IgE and asthma have been highlighted by the effect of this treatment and by basic research. In parallel, asthma phenotyping recently evolved to the concept of endotypes, relying on identified/suspected pathobiological mechanisms to phenotype patients, but has not yet clearly positioned IgE among biomarkers of asthma.In this review, we first summarise recent knowledge about the regulation of IgE production and its main receptor, FcεRI. In addition to allergens acting as classical IgE inducers, viral infections as well as air pollution may trigger the IgE pathway, notably resetting the threshold of IgE sensitivity by regulating FcεRI expression. We then analyse the place of IgE in different asthma endo/phenotypes and discuss the potential interest of IgE among biomarkers in asthma.
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
Lam EPS, Kariyawasam HH, Rana BMJ, et al., 2015, IL-25/IL-33–responsive TH2 cells characterize nasal polyps with a default TH17 signature in nasal mucosa, Journal of Allergy and Clinical Immunology, Vol: 137, Pages: 1514-1524, ISSN: 1097-6825
BackgroundChronic rhinosinusitis with nasal polyposis (CRSwNP) in Western countries is characterized by eosinophilia, IgE production, and TH2 cytokine expression. Type 2 innate lymphoid cells from polyps produce IL-5 and IL-13 in response to IL-25 and IL-33, although the relevance of this axis to local mucosal T-cell responses is unknown.ObjectiveWe sought to investigate the role of the IL-25/IL-33 axis in local mucosal T-cell responses in patients with CRSwNP.MethodsPolyp tissue and blood were obtained from patients undergoing nasal polypectomy. Control nasal biopsy specimens and blood were obtained from healthy volunteers. Tissue was cultured in a short-term explant model. T-cell surface phenotype/intracellular cytokines were assessed by means of flow cytometry. T-cell receptor variable β-chain analysis was performed with the immunoSEQ assay. Microarrays were performed for gene expression analysis.ResultsIL-25 receptor (IL-17RB)–expressing TH2 effector cells were identified in nasal polyp tissue but not the healthy nasal mucosa or periphery. IL-17RB+CD4+ polyp–derived TH2 cells coexpressed ST2 (IL-33 receptor) and responded to IL-25 and IL-33 with enhanced IL-5 and IL-13 production. Within IL-17RB+CD4+ T cells, several identical T-cell receptor variable β-chain complementarity-determining region 3 sequences were identified in different subjects, suggesting clonal expansion driven by a common antigen. Abundant IL-17–producing T cells were observed in both healthy nasal mucosal and polyp populations, with TH17-related genes the most overexpressed compared with peripheral blood T cells.ConclusionIL-25 and IL-33 can interact locally with IL-17RB+ST2+ polyp T cells to augment TH2 responses in patients with CRSwNP. A local TH17 response might be important in healthy nasal mucosal immune homeostasis.
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
Sharif HHHA, Ito C, Scadding GW, et al., 2015, Induction of circulating T follicular regulatory (Tfr) cells following grass pollen immunotherapy in patients with severe seasonal allergic rhinitis, Annual Meeting of the British-Society-for-Allergy-and-Clinical-Immunology, Publisher: WILEY-BLACKWELL, Pages: 1897-1897, ISSN: 0954-7894
Bousquet J, Schunemann HJ, Fonseca J, et al., 2015, MACVIA-ARIA Sentinel NetworK for allergic rhinitis (MASK-rhinitis): the new generation guideline implementation, Allergy, Vol: 70, Pages: 1372-1392, ISSN: 0105-4538
Several unmet needs have been identified in allergic rhinitis: identification of the time of onset of the pollen season, optimal control of rhinitis and comorbidities, patient stratification, multidisciplinary team for integrated care pathways, innovation in clinical trials and, above all, patient empowerment. MASK-rhinitis (MACVIA-ARIA Sentinel NetworK for allergic rhinitis) is a simple system centred around the patient which was devised to fill many of these gaps using Information and Communications Technology (ICT) tools and a clinical decision support system (CDSS) based on the most widely used guideline in allergic rhinitis and its asthma comorbidity (ARIA 2015 revision). It is one of the implementation systems of Action Plan B3 of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA). Three tools are used for the electronic monitoring of allergic diseases: a cell phone-based daily visual analogue scale (VAS) assessment of disease control, CARAT (Control of Allergic Rhinitis and Asthma Test) and e-Allergy screening (premedical system of early diagnosis of allergy and asthma based on online tools). These tools are combined with a clinical decision support system (CDSS) and are available in many languages. An e-CRF and an e-learning tool complete MASK. MASK is flexible and other tools can be added. It appears to be an advanced, global and integrated ICT answer for many unmet needs in allergic diseases which will improve policies and standards.
Pfaar O, Demoly P, van Wijk RG, et al., 2015, Recommendations for the standardization of clinical outcomes used in allergen immunotherapy trials for allergic rhinoconjunctivitis: an EAACI Position Paper, ALLERGOLOGIE, Vol: 38, Pages: 545-566, ISSN: 0344-5062
Gadermaier E, James LK, Shamji MH, et al., 2015, Epitope specificity determines cross-protection of a SIT-induced IgG4 antibody, Allergy, Vol: 71, Pages: 36-46, ISSN: 0105-4538
BackgroundThe calcium-binding 2EF-hand protein Phl p 7 from timothy grass pollen is a highly cross-reactive pollen pan-allergen that can induce severe clinical symptoms in allergic patients. Recently, a human monoclonal Phl p 7-specific IgG4 antibody (mAb102.1F10) was isolated from a patient who had received grass pollen-specific immunotherapy (SIT).MethodsWe studied epitope specificity, cross-reactivity, affinity and cross-protection of mAb102.1F10 towards homologous calcium-binding pollen allergens. Sequence comparisons and molecular modelling studies were performed with ClustalW and SPADE, respectively. Surface plasmon resonance measurements were made with purified recombinant allergens. Binding and cross-reactivity of patients' IgE and mAb102.1F10 to calcium-binding allergens and peptides thereof were studied with quantitative RAST-based methods, in ELISA, basophil activation and IgE-facilitated allergen presentation experiments.ResultsAllergens from timothy grass (Phl p 7), alder (Aln g 4), birch (Bet v 4), turnip rape (Bra r 1), lamb's quarter (Che a 3) and olive (Ole e 3, Ole e 8) showed high sequence similarity and cross-reacted with allergic patients' IgE. mAb102.1F10 bound the C-terminal portion of Phl p 7 in a calcium-dependent manner. It cross-reacted with high affinity with Ole e 3, whereas binding and affinity to the other allergens were low. mAb102.1F10 showed limited cross-inhibition of patients' IgE binding and basophil activation. Sequence comparison and surface exposure calculations identified three amino acids likely to be responsible for limited cross-reactivity.ConclusionsOur results demonstrate that a small number of amino acid differences among cross-reactive allergens can reduce the affinity of binding by a SIT-induced IgG and thus limit cross-protection.
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
Pillai P, Chan Y-C, Wu S-Y, et al., 2015, Omalizumab improves lung function despite treatment reduction, while reducing mucosal IgE expression in moderate to severe nonatopic asthma, Congress of the European-Academy-of-Allergy-and-Clinical-Immunology, Publisher: WILEY-BLACKWELL, Pages: 637-637, ISSN: 0105-4538
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