Publications
358 results found
Boyle RJ, Shamji MH, 2023, Food anaphylaxis in older people, CLINICAL AND EXPERIMENTAL ALLERGY, Vol: 53, Pages: 488-490, ISSN: 0954-7894
Bousquet J, Melén E, Haahtela T, et al., 2023, Rhinitis associated with asthma is distinct from rhinitis alone: The ARIA-MeDALL hypothesis, Allergy, Vol: 78, Pages: 1169-1203, ISSN: 0105-4538
Asthma, rhinitis, and atopic dermatitis (AD) are interrelated clinical phenotypes that partly overlap in the human interactome. The concept of "one-airway-one-disease," coined over 20 years ago, is a simplistic approach of the links between upper- and lower-airway allergic diseases. With new data, it is time to reassess the concept. This article reviews (i) the clinical observations that led to Allergic Rhinitis and its Impact on Asthma (ARIA), (ii) new insights into polysensitization and multimorbidity, (iii) advances in mHealth for novel phenotype definitions, (iv) confirmation in canonical epidemiologic studies, (v) genomic findings, (vi) treatment approaches, and (vii) novel concepts on the onset of rhinitis and multimorbidity. One recent concept, bringing together upper- and lower-airway allergic diseases with skin, gut, and neuropsychiatric multimorbidities, is the "Epithelial Barrier Hypothesis." This review determined that the "one-airway-one-disease" concept does not always hold true and that several phenotypes of disease can be defined. These phenotypes include an extreme "allergic" (asthma) phenotype combining asthma, rhinitis, and conjunctivitis. Rhinitis alone and rhinitis and asthma multimorbidity represent two distinct diseases with the following differences: (i) genomic and transcriptomic background (Toll-Like Receptors and IL-17 for rhinitis alone as a local disease; IL-33 and IL-5 for allergic and non-allergic multimorbidity as a systemic disease), (ii) allergen sensitization patterns (mono- or pauci-sensitization versus polysensitization), (iii) severity of symptoms, and (iv) treatment response. In conclusion, rhinitis alone (local disease) and rhinitis with asthma multimorbidity (systemic disease) should be considered as two distinct diseases, possibly modulated by the microbiome, and may be a model for understanding the epidemics of chronic and autoimmune diseases.
Pablo-Torres C, Izquierdo E, Tan TJ, et al., 2023, Deciphering the role of platelets in severe allergy by an integrative omics approach, ALLERGY, Vol: 78, Pages: 1319-1332, ISSN: 0105-4538
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- Citations: 2
Durham SR, Shamji MH, 2023, Allergen immunotherapy: past, present and future, NATURE REVIEWS IMMUNOLOGY, Vol: 23, Pages: 317-328, ISSN: 1474-1733
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- Citations: 30
Bousquet J, Sousa-Pinto B, Shamji MH, et al., 2023, Improvement of daily allergy control by sublingual immunotherapy: A MASK-air® study, CLINICAL AND EXPERIMENTAL ALLERGY, ISSN: 0954-7894
Del Giacco S, Shamji M, Torres M, et al., 2023, EAACI-Kongress 2023, 9. – 11. Juni 2023, ISSN: 0344-5062
Sousa-Pinto B, Jacome C, Pereira AM, et al., 2023, Development and validation of an electronic daily control score for asthma (e-DASTHMA): a real-world direct patient data study, LANCET DIGITAL HEALTH, Vol: 5, Pages: E227-E238
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- Citations: 2
Boyle RJ, Flohr C, Shamji MH, 2023, Global trends in eczema prevalence during early life, CLINICAL AND EXPERIMENTAL ALLERGY, Vol: 53, Pages: 252-254, ISSN: 0954-7894
Batard T, Canonica WG, Pfaar O, et al., 2023, Current advances in house dust mite allergen immunotherapy (AIT): Routes of administration, biomarkers and molecular allergen profiling., Mol Immunol, Vol: 155, Pages: 124-134
Allergy to house dust mites (HDM) is a perennial respiratory disease that affect more than half a billion people worldwide. Dermatophagoides pteronyssinus and D. farinae, two HDM species, are major sources of indoor allergens triggering allergic inflammation. Although symptomatic drugs are widely used to block the allergic reaction, allergen immunotherapy is the only curative treatment of IgE-mediated type I respiratory allergies. In this article, we review recent advances in various routes of allergen immunotherapy. We particularly focus on subcutaneous (SCIT) and sublingual (SLIT) immunotherapy, used as a reference therapy since they have transformed allergic treatments by improving symptoms (asthma and rhinitis) as well as the quality of life of patients. We also highlight recent data in more exploratory routes (i.e., oral, intralymphatic, epicutaneous and intradermal) and discuss respective advantages of various route, as well as their foreseen modes of action. Finally, we provide an update on biomarkers as well as on the relevance of the molecular profiling of allergic individuals related to treatment efficacy or asthma prediction.
Magnan A, Nicolas J-F, Caimmi D, et al., 2023, Deciphering Differential Behavior of Immune Responses as the Foundation for Precision Dosing in Allergen Immunotherapy., J Pers Med, Vol: 13, ISSN: 2075-4426
Like in many fields of medicine, the concept of precision dosing has re-emerged in routine practice in allergology. Only one retrospective study on French physicians' practice has addressed this topic so far and generated preliminary data supporting dose adaptation, mainly based on experience, patient profile understanding and response to treatment. Both intrinsic and extrinsic factors shape the individual immune system response to allergen immunotherapy (AIT). Herein, we focus on key immune cells (i.e., dendritic cells, innate lymphoid cells, B and T cells, basophils and mast cells) involved in allergic disease and its resolution to further understand the effect of AIT on the phenotype, frequency or polarization of these cells. We strive to discriminate differences in immune responses between responders and non-responders to AIT, and discuss the eligibility of a non/low-responder subset for dose adaptation. A differential behavior in immune cells is clearly observed in responders, highlighting the importance of conducting clinical trials with large cohorts of well-characterized subjects to decipher the immune mechanism of AIT. We conclude that there is a need for designing new clinical and mechanistic studies to support the scientific rationale of dose adaptation in the interest of patients who do not properly respond to AIT.
Layhadi J, Lobo RM, Ju TT, et al., 2023, Single-cell RNA-Seq identifies precise tolerogenic cellular and molecular pathways induced by depigmented-polymerized grass pollen allergen extract, Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology (AAAAI), Publisher: MOSBY-ELSEVIER, Pages: AB167-AB167, ISSN: 0091-6749
Shamji MH, Boyle RJ, 2023, Biological therapy practice, biomarkers of severe asthma and novel approaches for attaining immunomodulation in upper airway disease., Clin Exp Allergy, Vol: 53, Pages: 130-131
The hybrid rDer p 2231 stimulated in PBMCs isolated from atopic patients, higher levels of IL-2, IL-10, IL-15 and IFN-γ, as well as lower levels of IL-4, IL-5, IL-13, TNF-α and GM-CSF. The use of hybrid molecules as a therapeutic model in D. pteronyssinus allergic mice led to the reduction of IgE production and lower eosinophilic peroxidase activity in the airways. We found increased levels of IgG antibodies, which blocked the IgE binding to the parental allergens in serum of atopic patients. Furthermore, the stimulation of splenocytes from mice treated with rDer p 2231 induced higher levels of IL-10 and IFN-γ and decreased the secretion of IL-4 and IL-5, when compared to parental allergens and D. pteronyssinus extract. (7).
Layhadi J, Moya R, Tan TJ, et al., 2023, Single-cell RNA-Seq identifies precise tolerogenic cellular and molecular pathways induced by depigmented-polymerized grass pollen allergen extract, Journal of Allergy and Clinical Immunology, Vol: 151, Pages: 1357-1370.e9, ISSN: 0091-6749
Background:Immunological mechanism of action of allergoids remains poorly understood. Previous models of allergenicity and immunogenicity have yielded sub-optimal knowledge of these immunotherapeutic vaccine products. Novel single-cell RNA-seq technology offers a bridge to this gap in knowledge.Objective:To identify the underpinning tolerogenic molecular and cellular mechanisms of depigmented-polymerized Phleum pratense extract.MethodsThe molecular mechanisms underlying native Phleum pratense (Phl p), depigmented Phl p (DPG-Phl p), and depigmented-polymerized (DPG-POL-Phl p) allergoid were investigated using scRNA-seq. Allergen-specific Th2A, Tfh and IL-10+ Breg cells were quantified by flow cytometry in PBMCs from 16 grass pollen allergics (GPA) and 8 non-atopic controls (NAC). The ability of Phl p, DPG-Phl p and DPG-POL-Phl p to elicit FcεRI and FcεRII-mediated IgE responses was measured by basophil activation test and IgE-FAB assay.Results:ScRNA-seq analysis revealed that DPG-POL-Phl p downregulated genes associated with Th2 signaling, induced functional Tregs exhibiting immunosuppressive roles through CD52 and Siglec-10, modulated genes encoding immunoproteasome that dysregulate the processing and presentation of antigens to T cells and promoted a shift from IgE towards an IgA1 and IgG responses. In GPA, DPG-POL-Phl p exhibited reduced capacity to elicit proliferation of Th2A, IL-4+ Tfh and IL-21+ Tfh cells whilst being the most prominent at inducing CD19+CD5hiIL-10+ and CD19+CD5hiCD38intCD24intIL-10+ Breg cell subsets compared to Phl p (all, P<.05). Furthermore, DPG-POL-Phl p demonstrated a hypoallergenic profile through basophil activation and histamine release compared to Phl p (31.54-fold, P<.001).Conclusions:ScRNA-seq provides an in-depth resolution of the mechanisms underlying the tolerogenic profile of DPG-POL-Phl p.
Boyle RJ, Shamji MH, 2023, What does <i>Clinical and Experimental Allergy</i> mean by Trusted Evidence in Allergy'?, CLINICAL AND EXPERIMENTAL ALLERGY, Vol: 53, Pages: 4-6, ISSN: 0954-7894
Agache I, Shamji MH, Kermani NZ, et al., 2023, Multidimensional endotyping using nasal proteomics predicts molecular phenotypes in the asthmatic airways, Journal of Allergy and Clinical Immunology, Vol: 151, Pages: 128-137, ISSN: 0091-6749
BACKGROUND: Unsupervised clustering of biomarkers derived from non-invasive samples such as nasal fluid is less evaluated as a tool for describing asthma endotypes. OBJECTIVE: To evauate whether protein expression in nasal fluid would identify distinct clusters of asthmatics with specific lower airway molecular phenotypes. METHODS: Unsupervised clustering of 168 nasal inflammatory and immune proteins and Shapley values was used to stratify 43 severe asthmatic patients (ENDANA) using a two 'modelling blocks' machine learning (ML) approach. This algorithm was also applied to nasal brushings transcriptomics from U-BIOPRED. Feature reduction and functional gene analysis were used to compare proteomic and transcriptomic clusters. Gene set variation analysis (GSVA) provided enrichment scores (ESs) of the ENDANA protein signature within U-BIOPRED sputum and blood. RESULTS: The nasal protein ML model identified two severe asthma endotypes, which were replicated in U-BIOPRED nasal transcriptomics. Cluster 1 patients had significant airway obstruction, small airways disease, air trapping, decreased diffusing capacity and increased oxidative stress, although only 4/18 were current smokers. Shapley identified 20 cluster-defining proteins. Forty-one proteins were significantly higher in Cluster 1. Pathways associated with proteomic and transcriptomic clusters were linked to Th1, Th2, neutrophil, JAK-STAT, TLR and infection activation. GSVA analysis of the nasal protein and gene signatures were enriched in subjects with sputum neutrophilic/mixed granulocytic asthma and in subjects with a molecular phenotype found in sputum neutrophil-high subjects. CONCLUSIONS: Protein or gene analysis may indicate molecular phenotypes within the asthmatic lower airway and provide a simple, non-invasive test for non-T2 asthma that is currently unavailable.
Bousquet J, Anto JM, Sousa-Pinto B, et al., 2023, Digitally-enabled, patient-centred care in rhinitis and asthma multimorbidity: The ARIA-MASK-air<SUP>®</SUP> approach, CLINICAL AND TRANSLATIONAL ALLERGY, Vol: 13
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- Citations: 3
Tan TJ, Delgado-Dolset MI, Escribese MM, et al., 2022, Biomarkers of AIT: Models of prediction of efficacy, Allergologie, Vol: 45, Pages: 857-867, ISSN: 0344-5062
Allergic rhinitis is an IgE-mediated inflammation that remains a clinical challenge, affecting 40% of the UK population with a wide range of severity from nasal discomfort to life-threatening anaphylaxis. It can be managed by pharmacotherapeutics and in selected patients by allergen immunotherapy (AIT), which provides long-term clinical efficacy, especially during peak allergy season. However, there are no definitive biomarkers for AIT efficacy. Here, we aim to summarize the key adaptive, innate, humoral, and metabolic advances in biomarker identification in response to AIT. Mechanisms of efficacy consist of an immune deviation towards TH1-secreting IFN-γ, as well as an induction of IL10+ cTFR and TREG have been observed. TH2 cells undergo exhaustion after AIT due to chronic allergen exposure and correlates with the exhaustion markers PD-1, CTLA-4, TIGIT, and LAG3. IL10+ DCREG expressing C1Q and STAB are induced. KLRG1+IL10+ILC2 were shown to be induced in AIT in correlation with efficacy. BREG cells secreting IL-10, IL-35, and TGF-β are induced. Blocking antibodies IgG, IgA, and IgG4 are increased during AIT; whereas inflammatory metabolites, such as eicosanoids, are reduced. There are multiple promising biomarkers for AIT currently being evaluated. A panomic approach is essential to better understand cellular, molecular mechanisms and their correlation with clinical outcomes. Identification of predictive biomarkers of AIT efficacy will hugely impact current practice allowing physicians to select eligible patients that are likely to respond to treatment as well as improve patients' compliance to complete the course of treatment.
Shamji MH, Boyle RJ, 2022, Mepolizumab for eosinophilic chronic rhinosinusitis, loss of smell and challenges with accessibility to allergen immunotherapy, CLINICAL AND EXPERIMENTAL ALLERGY, Vol: 52, Pages: 1358-1360, ISSN: 0954-7894
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- Citations: 1
Agache I, Zemelka-Wiącek M, Shamji MH, et al., 2022, Immunotherapy: State-of-the-art review of therapies and theratypes., J Allergy Clin Immunol, Vol: 150, Pages: 1279-1288
Through its disease-modifying potential, immunotherapy is the keystone to curing allergic diseases. Allergen immunotherapy, applied for more than a century, is currently supported by novel modalities such as mAb-based therapies or small molecules targeting the key nodes of the allergic inflammation network. In this review, a summary of the most significant advances in immunotherapy is presented, addressing not only novel approaches to stratifying patients but also major controlled clinical trials and real-world evidence that strengthen the role of immunotherapy in the treatment of allergies.
Bousquet J, Sousa-Pinto B, Anto JM, et al., 2022, Identification by cluster analysis of patients with asthma and nasal symptoms using the MASK-air® mHealth app, PULMONOLOGY, Vol: 29, Pages: 292-305, ISSN: 2531-0437
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- Citations: 4
Boyle RJ, Shamji MH, 2022, Are paediatric allergy services promoting or harming public health?, CLINICAL AND EXPERIMENTAL ALLERGY, Vol: 52, Pages: 1238-1240, ISSN: 0954-7894
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- Citations: 2
Poto R, Shamji M, Marone G, et al., 2022, Neutrophil Extracellular Traps in Asthma: Friends or Foes?, CELLS, Vol: 11
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- Citations: 1
Shamji MH, Boyle RJ, 2022, Immunophenotyping and leukocyte redistribution in corticosteroid resistant severe asthma, CLINICAL AND EXPERIMENTAL ALLERGY, Vol: 52, Pages: 1126-1128, ISSN: 0954-7894
Farraia M, Paciencia I, Mendes FC, et al., 2022, Cost-effectiveness analysis of house dust mite allergen immunotherapy in children with allergic asthma, ALLERGY, Vol: 77, Pages: 2688-2698, ISSN: 0105-4538
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- Citations: 2
Bergmann C, Poli A, Agache I, et al., 2022, AllergoOncology: Danger signals in allergology and oncology: A European Academy of Allergy and Clinical Immunology (EAACI) Position Paper, ALLERGY, Vol: 77, Pages: 2594-2617, ISSN: 0105-4538
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- Citations: 2
Boyle RJ, Munblit D, Shamji MH, 2022, Patient-oriented allergy, CLINICAL AND EXPERIMENTAL ALLERGY, Vol: 52, Pages: 1012-1014, ISSN: 0954-7894
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- Citations: 1
Shamji MH, Boyle RJ, 2022, Immune modulation an COVID 19 in the Asia-Pacific region, CLINICAL AND EXPERIMENTAL ALLERGY, Vol: 52, Pages: 922-923, ISSN: 0954-7894
Jutel M, Torres MJ, Palomares O, et al., 2022, COVID-19 vaccination in patients receiving allergen immunotherapy (AIT) or biologicals-EAACI recommendations, ALLERGY, Vol: 77, Pages: 2313-2336, ISSN: 0105-4538
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- Citations: 10
Tan TJ, Layhadi JA, Shamji MH, 2022, Mechanisms and biomarkers of subcutaneous immunotherapy and sublingual immunotherapy in allergen immunotherapy, ALLERGY AND ASTHMA PROCEEDINGS, Vol: 43, Pages: 254-259, ISSN: 1088-5412
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- Citations: 4
Fieten KB, Drijver-Messelink MT, Cogo A, et al., 2022, Alpine altitude climate treatment for severe and uncontrolled asthma: An EAACI position paper, ALLERGY, Vol: 77, Pages: 1991-2024, ISSN: 0105-4538
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- Citations: 13
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