Publications
358 results found
Boyle RJ, Shamji MH, 2021, Allergy societies and the formula industry, CLINICAL AND EXPERIMENTAL ALLERGY, Vol: 51, Pages: 1260-1261, ISSN: 0954-7894
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- Citations: 7
Bousquet J, Agache I, Blain H, et al., 2021, Management of anaphylaxis due to COVID-19 vaccines in the elderly, ALLERGY, Vol: 76, Pages: 2952-2964, ISSN: 0105-4538
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- Citations: 13
Shamji MH, Boyle RJ, 2021, Unmet needs in food allergy, CLINICAL AND EXPERIMENTAL ALLERGY, Vol: 51, Pages: 1258-1259, ISSN: 0954-7894
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- Citations: 1
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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- Citations: 24
Warren CM, Snow TT, Lee AS, et al., 2021, Assessment of Allergic and Anaphylactic Reactions to mRNA COVID-19 Vaccines With Confirmatory Testing in a US Regional Health System, JAMA NETWORK OPEN, Vol: 4, ISSN: 2574-3805
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- Citations: 72
Boyle RJ, Shamji MH, 2021, Asthma management and impact on COVID-19 outcomes, CLINICAL AND EXPERIMENTAL ALLERGY, Vol: 51, Pages: 1100-1102, ISSN: 0954-7894
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- Citations: 1
De Kam P-J, Kramer MF, Shamji MH, et al., 2021, Dogmas, challenges, and promises in phase III allergen immunotherapy studies., World Allergy Organ J, Vol: 14, ISSN: 1939-4551
The concept of treatment of an allergy with the offending allergen was introduced more than a century ago. Allergen immunotherapy (AIT) is the only disease modifying treatment of allergic diseases caused by inhalational allergens and insect venoms. Despite this, only few AIT products have reached licensure in the US or an official marketing authorization status in European countries. Moreover, most of these AIT products are provided on an individual patient basis as named patient products (NPP) in Europe, while individualized preparations of (mixed) allergenic extract vials for subcutaneous administration (compounding) is common practice in the US. AIT products are generally considered safe and well tolerated, but the major practical clinical development challenge is to define the optimal dose and prove the efficacy and safety of these products using state-of-the art Phase II and pivotal Phase III studies. In planning Phase II-III AIT studies, a thorough understanding of the study challenges is essential (e.g. variability and non-validated status of subjective primary endpoints, limitations of pollen season definitions) and dogmas of these products (e.g., for sublingual immunotherapy (SLIT) trials double-blinding conditions cannot be maintained, resulting in stronger placebo responses in the active treatment group and inflated treatment effects in Phase III). There is future promise for more objective biomarker endpoints (e.g. basophil activation (CD63 and CD203c), subsets of regulatory dendritic, T and B cells, IL-10-producing group 2 innate lymphoid cells; alone or in combination) to overcome several of these dogmas and challenges; innovation in AIT clinical trials can only progress with integral biomarker research to complement the traditional endpoints in Phase II-III clinical development. The aim of this paper is to provide an overview of these dogmas, challenges and recommendations based on published data, to facilitate the design of Phase III studies and impr
Shamji MH, Palmer E, Layhadi JA, et al., 2021, Biological treatment in allergic disease, ALLERGY, Vol: 76, Pages: 2934-2937, ISSN: 0105-4538
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- Citations: 5
Shamji MH, Boyle RJ, 2021, Biomarkers in asthma and allergic diseases, CLINICAL AND EXPERIMENTAL ALLERGY, Vol: 51, Pages: 982-984, ISSN: 0954-7894
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- Citations: 1
Shamji MH, Singh I, Layhadi JA, et al., 2021, Passive Prophylactic Administration with a Single Dose of Anti-Fel d 1 Monoclonal Antibodies REGN1908-1909 in Cat Allergen-induced Allergic Rhinitis A Randomized, Double-Blind, Placebo-controlled Clinical Trial, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 204, Pages: 23-33, ISSN: 1073-449X
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- Citations: 30
Boyle RJ, Shamji MH, 2021, Evidence Synthesis in Allergy - A call for submissions, CLINICAL AND EXPERIMENTAL ALLERGY, Vol: 51, Pages: 868-869, ISSN: 0954-7894
Sokolowska M, Eiwegger T, Ollert M, et al., 2021, EAACI statement on the diagnosis, management and prevention of severe allergic reactions to COVID-19 vaccines, ALLERGY, Vol: 76, Pages: 1629-1639, ISSN: 0105-4538
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- Citations: 81
Klimek L, Jutel M, Akdis CA, et al., 2021, ARIA-EAACI statement on severe allergic reactions to COVID-19 vaccines - An EAACI-ARIA Position Paper, ALLERGY, Vol: 76, Pages: 1624-1628, ISSN: 0105-4538
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- Citations: 73
Sampath V, Rabinowitz G, Shah M, et al., 2021, Vaccines and Allergic reactions: The past, the current COVID-19 pandemic, and future perspectives, ALLERGY, Vol: 76, Pages: 1640-1660, ISSN: 0105-4538
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- Citations: 67
Shamji MH, Boyle RJ, 2021, Real word evidence studies: Is it the way forward?, CLINICAL AND EXPERIMENTAL ALLERGY, Vol: 51, Pages: 748-750, ISSN: 0954-7894
Bousquet J, Pfaar O, Agache I, et al., 2021, ARIA-EAACI care pathways for allergen immunotherapy in respiratory allergy, CLINICAL AND TRANSLATIONAL ALLERGY, Vol: 11
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- Citations: 16
Boyle RJ, Shamji MH, 2021, What does it mean to be food allergic?, CLINICAL AND EXPERIMENTAL ALLERGY, Vol: 51, Pages: 634-635, ISSN: 0954-7894
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- Citations: 2
Bousquet J, Jutel M, Pfaar O, et al., 2021, The Role of Mobile Health Technologies in Stratifying Patients for AIT and Its Cessation: The ARIA-EAACI Perspective., J Allergy Clin Immunol Pract, Vol: 9, Pages: 1805-1812
Allergen immunotherapy (AIT) is a proven therapeutic option for the treatment of allergic rhinitis and/or asthma. Many international or national practice guidelines have been produced, but the evidence-based method varies and they do not usually propose care pathways. The present article considers the possible role of mobile health in AIT for allergic rhinitis/asthma. There are no currently available validated biologic biomarkers that can predict AIT success, and mobile health biomarkers have some relevance. In the current article, the following aspects will be discussed: patient stratification for AIT, symptom-medication scores for the follow-up of patients, clinical trials, as well as the approach of the European Academy of Allergy and Clinical Immunology.
Alpan O, Layhadi JA, Ulrik Sonder S, et al., 2021, Basophil activation test: A diagnostic, predictive and monitoring assay for allergen immunotherapy, ALLERGY, Vol: 76, Pages: 1321-1324, ISSN: 0105-4538
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- Citations: 3
Shamji MH, Layhadi JA, Sharif H, et al., 2021, Immunological Responses and Biomarkers for Allergen-Specific Immunotherapy Against Inhaled Allergens, JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE, Vol: 9, Pages: 1769-1778, ISSN: 2213-2198
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- Citations: 40
Singh I, Beirag N, Kishore U, et al., 2021, Surfactant protein D: A therapeutic target for allergic airway diseases, The Collectin Protein Family and Its Multiple Biological Activities, Pages: 135-145, ISBN: 9783030670474
Surfactant protein D (SP-D), expressed in respiratory epithelium, is important for modulating both innate and adaptive immunity against inhaled allergens. This chapter evaluates the key immunomodulatory role of SP-D in allergic airway inflammatory events. Studies have shown that SP-D ameliorated various cellular mechanisms implicated in pulmonary allergic reactions, including allergic eosinophilia through induction of apoptosis and clearance of activated eosinophils, and inhibition of basophils activation. In addition, blocking allergen-specific IgE synthesis, T cell proliferation, and hindrance to the binding of allergen-IgE complex to B lymphocytes are also brought about by SP-D. In vitro, a recombinant fragment of human SP-D, composed of homotrimeric neck and C-type lectin domains (rfhSP-D), binds to allergens derived from Aspergillus fumigatus, house dust mite and grass pollen in a calcium-dependent manner and inhibits specific IgE interaction with allergens. Murine models of hypersensitivity reactions, when treated with rfhSP-D, showed reduced levels of IgE, clearance of peripheral and pulmonary eosinophilia, and Th2 polarisation to Th1 type. SP-D knock-out mice accordingly show hypereosinophilia and predominantly exaggerated Th2 response following allergen challenge; these features can be ameliorated by rfhSP-D treatment. The current state of the filed appears to suggest that rfhSP-D is an excellent therapeutic immunomodulator in airway allergic diseases.
Shamji M, Palmer E, Layhadi J, et al., 2021, Biological treatment provides disease-modifying immunological effects
<jats:p id="p1">Advances in molecular biology alongside the accelerated development ofgene and cell engineering have contributed to the development of severalendotype-targeted biological therapies against chronic immune-mediatedallergic diseases. Conventional therapies for asthma, chronicrhinosinusitis with polyposis (CRSwNP), chronic spontaneous urticariaand atopic dermatitis (AD) are not without limitations, and as such theadvent of biological therapies have provided a promising alternativetreatment option. Biologicals have proven efficacious in the treatmentof refractory chronic spontaneous urticaria, asthma, AD, CRSwNP andthere is increasing evidence for their utility in treating food allergy.Biologicals are applied and investigated for the most urgent need: acutetreatment, symptom control and reduction of steroid usage. Currentlythere are five approved biologicals for allergic disease management,targeted against IgE (omalizumab), type 2 (T2) cytokines and cytokinereceptors (IL-4Ra; dupilumab, IL-5; mepolizumab/reslizumab, IL-5Ra;benralizumab).</jats:p>
Layhadi JA, Shamji MH, 2021, Uncovering the immunological properties of isolated lymphoid follicles, ALLERGY, Vol: 76, Pages: 1292-1293, ISSN: 0105-4538
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- Citations: 5
Shamji MH, Boyle RJ, 2021, New innovations in allergy treatment and phenotyping, CLINICAL AND EXPERIMENTAL ALLERGY, Vol: 51, Pages: 514-517, ISSN: 0954-7894
Shamji M, Valenta R, Jardetzky T, et al., 2021, The role of IgE, IgG, and IgA in tolerance, sensitization, and targeted treatment of allergic disease
<jats:p id="p1">Immunoglobulin E (IgE)-mediated allergy is the most commonhypersensitivity disease affecting more than 30% of the population. Ingenetically-predisposed subjects exposure to minute quantities ofallergens leads to the production of IgE antibodies which is termedallergic sensitization and mainly occurs in early childhood.Allergen-specific IgE then binds to the high (FcRI) and low affinityreceptors (FcRII, also called CD23) for IgE on effector cells andantigen-presenting cells, respectively. Subsequent and repeated allergenexposure increases allergen-specific IgE levels and, by receptorcross-linking, triggers immediate release of inflammatory mediators frommast cells and basophils whereas IgE-facilitated allergen presentationperpetuates T cell-mediated allergic inflammation. Due to engagement ofreceptors which are highly selective for IgE even tiny amounts ofallergens can induce massive inflammation. Naturally occurringallergen-specific IgG and IgA antibodies usually recognize differentepitopes on allergens compared to IgE, and do not efficiently interferewith allergen-induced inflammation. However IgG and IgA antibodies tothese important IgE epitopes can be induced by allergen-specificimmunotherapy or by passive immunization. These will lead to competitionwith IgE for binding with the allergen and prevent allergic responses.Similarly, anti-IgE treatment does the same by preventing IgE frombinding to its receptor on mastcells and basophils. Here we review thecomplex interplay of allergen-specific IgE, IgG and IgA and thecorresponding cell receptors in allergic diseases and its relevance fordiagnosis, treatment and prevention of allergy.</jats:p>
Pfaar O, Agache I, Bergmann K-C, et al., 2021, Placebo effects in allergen immunotherapy-An EAACI Task Force Position Paper, ALLERGY, Vol: 76, Pages: 629-647, ISSN: 0105-4538
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- Citations: 27
Boyle RJ, Shamji MH, 2021, Aetiology and prevention of eczema, CLINICAL AND EXPERIMENTAL ALLERGY, Vol: 51, Pages: 380-381, ISSN: 0954-7894
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- Citations: 1
Sahiner UM, Layhadi JA, Golebski K, et al., 2021, Innate Lymphoid Cells: The Missing Part Of A Puzzle In Food Allergy., Allergy
Food allergy is an increasingly prevalent disease which is mainly driven by uncontrolled type 2 immune response. Currently, knowledge about the underlying mechanisms that initiate and promote the immune response to dietary allergens is limited. Patients with food allergy are commonly sensitized through the skin in their early life, later on developing allergy symptoms within the gastrointestinal tract. Food allergy results from a dysregulated type 2 response to food allergens, characterized by enhanced levels of IgE, IL-4, IL-5 and IL-13 with infiltration of mast cells, eosinophils and basophils. Recent studies raised a possible role for the involvement of innate lymphoid cells (ILCs) in driving food allergy. They represent a group of lymphocytes that lack specific, recombined antigen receptors. ILCs contribute to immune responses not only by releasing cytokines and other mediators but also by responding to cytokines produced by activated cells in their local microenvironment. Due to their localization at barrier surfaces ofthe airways, gut and skin, ILCs form a link between the innate and adaptive immunity. This review summarizes recent evidence on how skin and gastrointestinal mucosal immune system contribute to both homeostasis and the development of food allergy, as well as the involvement of ILCs towards inflammatory processes and regulatory mechanisms.
Golebski K, Layhadi JA, Sahiner U, et al., 2021, Induction of IL-10-producing type 2 innate lymphoid cells by allergen immunotherapy is associated with clinical response., Immunity, Vol: 54, Pages: 291-307.e7, ISSN: 1074-7613
The role of innate immune cells in allergen immunotherapy that confers immune tolerance to the sensitizing allergen is unclear. Here, we report a role of interleukin-10-producing type 2 innate lymphoid cells (IL-10+ ILC2s) in modulating grass-pollen allergy. We demonstrate that KLRG1+ but not KLRG1- ILC2 produced IL-10 upon activation with IL-33 and retinoic acid. These cells attenuated Th responses and maintained epithelial cell integrity. IL-10+ KLRG1+ ILC2s were lower in patients with grass-pollen allergy when compared to healthy subjects. In a prospective, double-blind, placebo-controlled trial, we demonstrated that the competence of ILC2 to produce IL-10 was restored in patients who received grass-pollen sublingual immunotherapy. The underpinning mechanisms were associated with the modification of retinol metabolic pathway, cytokine-cytokine receptor interaction, and JAK-STAT signaling pathways in the ILCs. Altogether, our findings underscore the contribution of IL-10+ ILC2s in the disease-modifying effect by allergen immunotherapy.
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.
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