306 results found
Sampath V, Shalakhti O, Veidis E, et al., 2023, Acute and Chronic Impacts of Heat Stress on Planetary Health., Allergy
Heat waves are increasing in intensity, frequency, and duration causing significant heat stress in all living organisms. Heat stress has multiple negative effects on plants affecting photosynthesis, respiration, growth, development, and reproduction. It also impacts animals leading to physiological and behavioral alterations, such as reduced caloric intake, increased water intake, and decreased reproduction and growth. In humans, epidemiological studies have shown that heat waves are associated with increased morbidity and mortality. There are many biological effects of heat stress (structural changes, enzyme function disruption, damage through reactive oxygen or nitrogen species). While plants and animals can mitigate some of these effects through adaptive mechanisms such as the generation of heat shock proteins, antioxidants, stress granules, and others, these mechanisms may likely be inadequate with further global warming. This review summarizes the effects of heat stress on plants and animals and the adaptative mechanisms that have evolved to counteract this stress.
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.
Bousquet J, Melén E, Haahtela T, et al., 2023, Rhinitis associated with asthma is distinct from rhinitis alone: The ARIA-MeDALL hypothesis., Allergy
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 polysensitisation and multimorbidity, (iii) advances in mHealth for novel phenotype definition, (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 sensitisation patterns (mono- or pauci-sensitisation versus polysensitisation), (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 auto-immune diseases.
Shamji MH, Ollert M, Adcock IM, et al., 2023, EAACI guidelines on environmental science in allergic diseases and asthma - Leveraging artificial intelligence and machine learning to develop a causality model in exposomics, ALLERGY, ISSN: 0105-4538
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.
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, 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.
Pablo-Torres C, Izquierdo E, Tan TJ, et al., 2023, Deciphering the role of platelets in severe allergy by an integrative omics approach, ALLERGY, ISSN: 0105-4538
Boyle RJ, Shamji MH, 2023, What does Clinical and Experimental Allergy mean by Trusted Evidence in Allergy'?, CLINICAL AND EXPERIMENTAL ALLERGY, Vol: 53, Pages: 4-6, ISSN: 0954-7894
Bousquet J, Anto JM, Sousa-Pinto B, et al., 2023, Digitally-enabled, patient-centred care in rhinitis and asthma multimorbidity: The ARIA-MASK-air((R)) approach, CLINICAL AND TRANSLATIONAL ALLERGY, Vol: 13
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.
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
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
BACKGROUND: The self-reporting of asthma frequently leads to patient misidentification in epidemiological studies. Strategies combining the triangulation of data sources may help to improve the identification of people with asthma. We aimed to combine information from the self-reporting of asthma, medication use and symptoms to identify asthma patterns in the users of an mHealth app. METHODS: We studied MASK-air® users who reported their daily asthma symptoms (assessed by a 0-100 visual analogue scale - "VAS Asthma") at least three times (either in three different months or in any period). K-means cluster analysis methods were applied to identify asthma patterns based on: (i) whether the user self-reported asthma; (ii) whether the user reported asthma medication use and (iii) VAS asthma. Clusters were compared by the number of medications used, VAS asthma levels and Control of Asthma and Allergic Rhinitis Test (CARAT) levels. FINDINGS: We assessed a total of 8,075 MASK-air® users. The main clustering approach resulted in the identification of seven groups. These groups were interpreted as probable: (i) severe/uncontrolled asthma despite treatment (11.9-16.1% of MASK-air® users); (ii) treated and partly-controlled asthma (6.3-9.7%); (iii) treated and controlled asthma (4.6-5.5%); (iv) untreated uncontrolled asthma (18.2-20.5%); (v) untreated partly-controlled asthma (10.1-10.7%); (vi) untreated controlled asthma (6.7-8.5%) and (vii) no evidence of asthma (33.0-40.2%). This classification was validated in a study of 192 patients enrolled by physicians. INTERPRETATION: We identified seven profiles based on the probability of having asthma and on its level of control. mHealth tools are hypothesis-generating and complement classical epidemiological approaches in identifying patients with asthma.
Poto R, Shamji M, Marone G, et al., 2022, Neutrophil Extracellular Traps in Asthma: Friends or Foes?, CELLS, Vol: 11
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
Durham SR, Shamji MH, 2022, Allergen immunotherapy: past, present and future, NATURE REVIEWS IMMUNOLOGY, ISSN: 1474-1733
- Author Web Link
- Citations: 3
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
Boyle RJ, Munblit D, Shamji MH, 2022, Patient-oriented allergy, CLINICAL AND EXPERIMENTAL ALLERGY, Vol: 52, Pages: 1012-1014, ISSN: 0954-7894
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
Labella M, Cespedes JA, Dona I, et al., 2022, Reply to correspondence: Basophil reactivity to BNT162b2 in COVID-19 convalescence, ALLERGY, Vol: 77, Pages: 2266-2267, ISSN: 0105-4538
Shamji MH, Boyle RJ, Roberts G, 2022, Prize-winning abstracts from BSACI/WAO 2022 meeting, CLINICAL AND EXPERIMENTAL ALLERGY, Vol: 52, Pages: 830-832, ISSN: 0954-7894
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
- Author Web Link
- Citations: 3
Boyle RJ, Shamji MH, 2022, Clinical and Experimental Allergy boycotts formula advertising, CLINICAL AND EXPERIMENTAL ALLERGY, Vol: 52, Pages: 828-829, ISSN: 0954-7894
Shamji MH, Boyle RJ, 2022, Biomarkers of airway inflammation and immunotherapy, CLINICAL AND EXPERIMENTAL ALLERGY, Vol: 52, Pages: 726-728, 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
Boyle RJ, Shamji MH, 2022, Early origins of allergic disease, CLINICAL AND EXPERIMENTAL ALLERGY, Vol: 52, Pages: 592-594, ISSN: 0954-7894
Farraia M, Paciencia I, Castro Mendes F, et al., 2022, Allergen immunotherapy for asthma prevention: A systematic review and meta-analysis of randomized and non-randomized controlled studies, ALLERGY, Vol: 77, Pages: 1719-1735, ISSN: 0105-4538
- Author Web Link
- Citations: 7
Shamji MH, Boyle RJ, 2022, Immune modulation and the role of innate immune cells in allergy and asthma, CLINICAL AND EXPERIMENTAL ALLERGY, Vol: 52, Pages: 474-475, ISSN: 0954-7894
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