Imperial College London

ProfessorMohamedShamji

Faculty of MedicineNational Heart & Lung Institute

Professor of Immunology and Allergy
 
 
 
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Contact

 

+44 (0)20 7594 3476m.shamji99 Website

 
 
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Location

 

Room 111Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Publication Type
Year
to

353 results found

Starchenka S, Oluwayi K, Heath M, Armfield O, Shamji M, Layhadi J, Lis K, Cadavez L, Rusyn O, Skinner M, De Kam P-Jet al., 2024, Peripheral blood mononuclear cell transcriptome profile in a clinical trial with subcutaneous, grass pollen allergoid immunotherapy., Clin Exp Allergy, Vol: 54, Pages: 130-142

INTRODUCTION: Allergen-specific immunotherapy (AIT) is the only disease-modifying treatment in allergic airway diseases. Underlying immunological mechanisms and candidate biomarkers, which may be translated into predictive/surrogate measures of clinical efficacy, remain an active area of research. The aim of this study was to evaluate Pollinex Quattro (PQ) Grass AIT induced immunomodulatory mechanisms, based on transcriptome profiling of peripheral blood mononuclear cells. METHODS: 119 subjects with grass pollen induced seasonal allergic rhinitis (SAR) were randomized in a 2:2:1:1 ratio to receive a cumulative dose of PQ Grass as a conventional or extended pre-seasonal regimen, placebo, or placebo with MicroCrystalline Tyrosine. Gene expression analysis was an exploratory endpoint evaluated in a subgroup of 30 subjects randomly selected from the four treatment arms. Samples were collected at three time points: screening (baseline), before the start of the grass pollen season and at the end of the season. This study was funded by the manufacturer of PQ. RESULTS: Transcriptome analysis demonstrated that the most significant changes in gene expression, for both treatment regimens, were at the end of the grass pollen season, with the main Th1 candidate molecules (IL-12A, IFNγ) upregulated and Th2 signature cytokines downregulated (IL-4, IL-13, IL-9) (p < .05). Canonical pathways analysis demonstrated Th1, Th2, Th17 and IL-17 as the most significantly enriched pathways based on absolute value of activation z-score (IzI score ≥ 2, p < .05). Upstream regulator analysis showed pronounced inhibition of pro-inflammatory allergic molecules IgE, IL-17A, IL-17F, IL-25 (IL-17E) (IzI score ≥ 2, FDR < 0.05) and activation of pro-tolerogenic molecules IL-12A, IL-27, IL-35 (EBI3) at the end of the grass pollen season. CONCLUSION: Peripheral blood mononuclear cells transcriptome profile showed a

Journal article

Pascal M, Edelman SM, Nopp A, Möbs C, Geilenkeuser WJ, Knol EF, Ebo DG, Mertens C, Shamji MH, Santos AF, Patil S, Eberlein B, Mayorga C, Hoffmann HJet al., 2024, EAACI task force report: A consensus protocol for the basophil activation test for collaboration and external quality assurance., Allergy, Vol: 79, Pages: 290-293

Journal article

Busold S, Aglas L, Menage C, Desgagnés R, Faye L, Fitchette A-C, de Jong EC, Martel C, Stigler M, Catala-Stordeur V, Tropper G, Auger L, Morel B, Versteeg SA, Vézina L-P, Gomord V, Layhadi JA, Shamji M, Geijtenbeek TBH, van Ree Ret al., 2024, Plant-produced Der p 2-bearing bioparticles activate Th1/Treg-related activation patterns in dendritic cells irrespective of the allergic background., Clin Exp Allergy

Journal article

Layhadi JA, Lalioti A, Palmer E, van Zelm MC, Wambre E, Shamji MHet al., 2024, Mechanisms and predictive biomarkers of allergen immunotherapy in the clinic, Journal of Allergy and Clinical Immunology: In Practice, Vol: 12, Pages: 59-66, ISSN: 2213-2198

Allergen-specific immunotherapy (AIT) remains the only disease-modifying treatment for IgE-mediated allergic diseases such as allergic rhinitis (AR). It can provide long-term clinical benefits when given for three years or longer. Mechanisms of immune tolerance induction by AIT are underscored by the modulation of several compartments within the immune system. These include repair of disruption in epithelial barrier integrity, modulation of the innate immune compartment that includes regulatory dendritic cells (DCreg) and innate lymphoid cells (ILCreg), and adaptive immune compartments such as induction of regulatory T and B cells. Altogether, these are also associated with dampening allergen-specific Th2 (Th2A) and T follicular helper cell responses and subsequent generation of blocking antibodies. Whilst AIT is effective in modifying the immune response, there is a lack of validated and clinically relevant biomarkers that can be used to monitor desensitization, efficacy, and the likelihood of response, all of which can contribute to accelerating personalized medication and increasing patient care. Candidate biomarkers comprise humoral, cellular, metabolic and in vivo biomarkers; however, these are primarily studied in small trials and require further validation. In this review, we evaluate the current candidates of biomarkers of AIT and how we can implement changes in future studies to help us identify clinically relevant biomarkers of safety, compliance and efficacy.

Journal article

Shamji MH, Li J, 2024, Immunotherapy in the Clinic., J Allergy Clin Immunol Pract, Vol: 12, Pages: 67-68

Journal article

Hoof I, Bønnelykke K, Stranzl T, Brand S, Li X, Shamji MH, Meyers DA, Bateman ED, Bleecker E, Andersen PSet al., 2023, Genetic and T2 biomarkers linked to the efficacy of HDM sublingual immunotherapy in asthma., Thorax

BACKGROUND: Hypersensitivity to house dust mite (HDM) allergens is a common cause of allergic asthma symptoms and can be effectively treated with allergy immunotherapy (AIT). OBJECTIVE: To investigate whether genetic and type 2 (T2) inflammatory biomarkers correlate with disease severity in subjects with allergic asthma, and whether this can be modified by AIT. METHODS: MITRA (NCT01433523) was a phase III, randomised, double-blind, placebo-controlled trial of HDM sublingual immunotherapy (SLIT)-tablets in adults with HDM allergic asthma. Post hoc analyses of the study population (N=742) evaluated associations between T2 inflammatory (blood eosinophils, eosinophil cationic protein (ECP), total IgE and tryptase) and genetic (single-nucleotide polymorphisms, SNP) biomarkers (n=582) for the primary study endpoint (time to first moderate/severe asthma exacerbation). SNP associations were verified in HDM-positive subgroup from an independent 3-year Severe Asthma Research Programme (SARP3) subject cohort. RESULTS: An increased asthma exacerbation risk in subjects homozygous for SNP rs7216389 (chromosomal locus 17q12-21) was reduced (p=0.037) by treatment with HDM SLIT (HR=0.37 (95% CI 0.22 to 0.64), p<0.001). The associations between exacerbation risk and 17q12-21 SNPs were replicated in the SARP3 HDM-positive subgroup. High levels of T2 biomarkers were associated with increased risk of asthma exacerbations in the placebo group. HDM SLIT-tablet treatment reduced this risk (blood eosinophils: HR=0.50 (95% CI 0.30 to 0.85); ECP: HR=0.45 (95% CI 0.29 to 0.87); tryptase: HR=0.45 (95% CI 0.25 to 0.80)). The treatment effect was higher (p=0.006) for subjects with a higher number of elevated T2 biomarkers. CONCLUSIONS: HDM SLIT-tablet AIT is efficacious in HDM-sensitised asthma subjects with a genetic asthma predisposition and/or an underlying T2 endotype. TRIAL REGISTRATION NUMBER: NCT01433523.

Journal article

Shamji MH, Boyle RJ, Roberts G, 2023, Prize-winning abstracts from the BSACI 2023 meeting., Clin Exp Allergy, Vol: 53, Pages: 1234-1235

Journal article

Zemelka-Wiacek M, Agache I, Akdis CA, Akdis M, Casale TB, Dramburg S, Jahnz-Różyk K, Kosowska A, Matricardi PM, Pfaar O, Shamji MH, Jutel Met al., 2023, Hot topics in allergen immunotherapy, 2023: Current status and future perspective., Allergy

The importance of allergen immunotherapy (AIT) is multifaceted, encompassing both clinical and quality-of-life improvements and cost-effectiveness in the long term. Key mechanisms of allergen tolerance induced by AIT include changes in memory type allergen-specific T- and B-cell responses towards a regulatory phenotype with decreased Type 2 responses, suppression of allergen-specific IgE and increased IgG1 and IgG4 , decreased mast cell and eosinophil numbers in allergic tissues and increased activation thresholds. The potential of novel patient enrolment strategies for AIT is taking into account recent advances in biomarkers discoveries, molecular allergy diagnostics and mobile health applications contributing to a personalized approach enhancement that can increase AIT efficacy and compliance. Artificial intelligence can help manage and interpret complex and heterogeneous data, including big data from omics and non-omics research, potentially predict disease subtypes, identify biomarkers and monitor patient responses to AIT. Novel AIT preparations, such as synthetic compounds, innovative carrier systems and adjuvants, are also of great promise. Advances in clinical trial models, including adaptive, complex and hybrid designs as well as real-world evidence, allow more flexibility and cost reduction. The analyses of AIT cost-effectiveness show a clear long-term advantage compared to pharmacotherapy. Important research questions, such as defining clinical endpoints, biomarkers of patient selection and efficacy, mechanisms and the modulation of the placebo effect and alternatives to conventional field trials, including allergen exposure chamber studies are still to be elucidated. This review demonstrates that AIT is still in its growth phase and shows immense development prospects.

Journal article

Altman MC, Segnitz RM, Larson D, Jayavelu ND, Smith M, Patel S, Scadding GW, Qin T, Sanda S, Steveling E, Eifan AO, Penagos M, Jacobson MR, Parkin RV, Shamji MH, Togias A, Durham SRet 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.

Journal article

Xu Z, Huang Y, Meese T, Van Nevel S, Holtappels G, Vanhee S, Broeker BM, Li Z, de Meester E, De Ruyck N, Van Zele T, Gevaert P, Van Nieuwerburgh F, Zhang L, Shamji MH, Wen W, Zhang N, Bachert Cet al., 2023, The multi-omics single-cell landscape of sinus mucosa in uncontrolled severe chronic rhinosinusitis with nasal polyps, CLINICAL IMMUNOLOGY, Vol: 256, ISSN: 1521-6616

Journal article

Shamji MH, Boyle RJ, 2023, Management of childhood asthma and tools to evaluate asthma pathophysiology., Clin Exp Allergy, Vol: 53, Pages: 1138-1140

Journal article

Mösges R, Zeyen C, Raskopf E, Acikel C, Sahin H, Allekotte S, Cuevas M, Shamji MH, Subiza JL, Casanovas Met al., 2023, A randomized, double-blind, placebo-controlled trial with mannan-conjugated birch pollen allergoids., Allergy

BACKGROUND: There is still great need to develop new strategies to improve the efficacy of allergen immunotherapies with optimal safety standards for patients. A new promising approach is to couple allergoids to mannan. The objective of this phase IIa/IIb study was to identify the optimal dose of mannan-conjugated birch pollen allergoids for the short-course treatment of birch pollen-induced allergic rhinoconjunctivitis. METHODS: For this prospective, randomized, double-blind, placebo-controlled, dose-finding study, 246 birch pollen-allergic adults received 0.5 mL placebo or 1000, 3000 or 10,000 mTU/mL of mannan-conjugated birch pollen allergoids at five pre-seasonal visits. Efficacy was assessed by comparing allergic rhinoconjunctivitis symptoms and use of anti-allergic medication during the peak of the birch pollen season 2020. Immunologic, tolerability and safety effects were also analysed. RESULTS: The highest dose of mannan-conjugated birch pollen allergoids reduced the combined symptom and medication score during the peak birch pollen season by a median of 24.7% compared to placebo. The production of Bet v 1 specific IgG4 significantly increased in a dose-dependent manner (3.6- and 4.5-fold) in the 3000 and 10,000 mTU/mL groups. The Bet v 1 specific IgE/IgG4 ratio was also strongly reduced (up to -70%). No fatalities nor serious adverse events were reported, and no adrenaline was used. In total, four systemic reactions occurred (two grade I and two grade II). CONCLUSION: All doses of mannan-conjugated birch pollen allergoids can be considered as safe. Since the application of 10,000 mTU/mL resulted in the highest efficacy, this dose qualifies for further investigation.

Journal article

Jutel M, Agache I, Zemelka-Wiacek M, Akdis M, Chivato T, del Giacco S, Gajdanowicz P, Gracia IE, Klimek L, Lauerma A, Ollert M, O'Mahony L, Schwarze J, Shamji MH, Skypala I, Palomares O, Pfaar O, Torres MJ, Bernstein JA, Cruz AA, Durham SR, Galli SJ, Gomez RM, Guttman-Yassky E, Haahtela T, Holgate ST, Izuhara K, Kabashima K, Larenas-Linnemann DE, von Mutius E, Nadeau KC, Pawankar R, Platts-Mills TAE, Sicherer SH, Park H-S, Vieths S, Wong G, Zhang L, Bilo MB, Akdis CAet al., 2023, Nomenclature of allergic diseases and hypersensitivity reactions: Adapted to modern needs: An EAACI position paper, ALLERGY, ISSN: 0105-4538

Journal article

Boyle RJ, Shamji MH, Skypala IJ, Garcia-Larssen Vet al., 2023, Nutrition and Allergy., Clin Exp Allergy, Vol: 53, Pages: 982-983

Journal article

Boyle RJ, Shamji MH, 2023, Adrenaline auto-injectors for people at risk of anaphylaxis, CLINICAL AND EXPERIMENTAL ALLERGY, Vol: 53, Pages: 896-898, ISSN: 0954-7894

Journal article

Sousa-Pinto B, Louis R, Anto JM, Amaral R, Sá-Sousa A, Czarlewski W, Brussino L, Canonica GW, Chaves Loureiro C, Cruz AA, Gemicioglu B, Haahtela T, Kupczyk M, Kvedariene V, Larenas-Linnemann DE, Okamoto Y, Ollert M, Pfaar O, Pham-Thi N, Puggioni F, Regateiro FS, Romantowski J, Sastre J, Scichilone N, Taborda-Barata L, Ventura MT, Agache I, Bedbrook A, Becker S, Bergmann KC, Bosnic-Anticevich S, Bonini M, Boulet L-P, Brusselle G, Buhl R, Cecchi L, Charpin D, de Blay F, Del Giacco S, Ivancevich JC, Jutel M, Klimek L, Kraxner H, Kuna P, Laune D, Makela M, Morais-Almeida M, Nadif R, Niedoszytko M, Papadopoulos NG, Papi A, Patella V, Pétré B, Rivero Yeverino D, Robalo Cordeiro C, Roche N, Rouadi PW, Samolinski B, Savouré M, Shamji MH, Sheikh A, Suppli Ulrik C, Usmani OS, Valiulis A, Yorgancioglu A, Zuberbier T, Fonseca JA, Costa EM, Bousquet Jet al., 2023, Adherence to inhaled corticosteroids and long-acting β2-agonists in asthma: A MASK-air study., Pulmonology

INTRODUCTION: Adherence to controller medication is a major problem in asthma management, being difficult to assess and tackle. mHealth apps can be used to assess adherence. We aimed to assess the adherence to inhaled corticosteroids+long-acting β2-agonists (ICS+LABA) in users of the MASK-air® app, comparing the adherence to ICS+formoterol (ICS+F) with that to ICS+other LABA. MATERIALS AND METHODS: We analysed complete weeks of MASK-air® data (2015-2022; 27 countries) from patients with self-reported asthma and ICS+LABA use. We compared patients reporting ICS+F versus ICS+other LABA on adherence levels, symptoms and symptom-medication scores. We built regression models to assess whether adherence to ICS+LABA was associated with asthma control or short-acting beta-agonist (SABA) use. Sensitivity analyses were performed considering the weeks with no more than one missing day. RESULTS: In 2598 ICS+LABA users, 621 (23.9%) reported 4824 complete weeks and 866 (33.3%) reported weeks with at most one missing day. Higher adherence (use of medication ≥80% of weekly days) was observed for ICS+other LABA (75.1%) when compared to ICS+F (59.3%), despite both groups displaying similar asthma control and work productivity. The ICS+other LABA group was associated with more days of SABA use than the ICS+F group (median=71.4% versus 57.1% days). Each additional weekly day of ICS+F use was associated with a 4.1% less risk in weekly SABA use (95%CI=-6.5;-1.6%;p=0.001). For ICS+other LABA, the percentage was 8.2 (95%CI=-11.6;-5.0%;p<0.001). CONCLUSIONS: In asthma patients adherent to the MASK-air app, adherence to ICS+LABA was high. ICS+F users reported lower adherence but also a lower SABA use and a similar level of control.

Journal article

Sampath V, Shalakhti O, Veidis E, Efobi JAI, Shamji MH, Agache I, Skevaki C, Renz H, Nadeau KCet al., 2023, Acute and chronic impacts of heat stress on planetary health, ALLERGY, Vol: 78, Pages: 2109-2120, ISSN: 0105-4538

Journal article

Shamji MH, Boyle RJ, 2023, Immunotherapy and prevention of allergic diseases., Clin Exp Allergy, Vol: 53, Pages: 788-790

Journal article

Kappen J, Diamant Z, Agache I, Bonini M, Bousquet J, Canonica GW, Durham SRR, Guibas GVV, Hamelmann E, Jutel M, Papadopoulos NGG, Roberts G, Shamji MHH, Zieglmayer P, van Wijk RG, Pfaar Oet al., 2023, Standardization of clinical outcomes used in allergen immunotherapy in allergic asthma: An EAACI position paper, ALLERGY, ISSN: 0105-4538

Journal article

Bousquet J, Shamji MH, Anto JM, Schuenemann HJ, Canonica GW, Jutel M, Del Giacco S, Zuberbier T, Pfaar O, Fonseca JA, Sousa-Pinto B, Klimek L, Czarlewski W, Bedbrook A, Amaral R, Ansotegui IJ, Bosnic-Anticevich S, Braido F, Chaves Loureiro C, Gemicioglu B, Haahtela T, Kulus M, Kuna P, Kupczyk M, Matricardi PM, Regateiro FS, Samolinski B, Sofiev M, Toppila-Salmi S, Valiulis A, Ventura MT, Barbara C, Bergmann KC, Bewick M, Blain H, Bonini M, Boulet L-P, Bourret R, Brusselle G, Brussino L, Buhl R, Cardona V, Casale T, Cecchi L, Charpin D, Cherrez-Ojeda I, Chu DK, Cingi C, Costa EM, Cruz AA, Devillier P, Dramburg S, Fokkens WJ, Gotua M, Heffler E, Ispayeva Z, Ivancevich JC, Joos G, Kaidashev I, Kraxner H, Kvedariene V, Larenas-Linnemann DE, Laune D, Lourenco O, Louis R, Makela M, Makris M, Maurer M, Melen E, Micheli Y, Morais-Almeida M, Mullol J, Niedoszytko M, O'Hehir R, Okamoto Y, Olze H, Papadopoulos NG, Papi A, Patella V, Petre B, Pham-Thi N, Puggioni F, Quirce S, Roche N, Rouadi PW, Sa-Sousa A, Sagara H, Sastre J, Scichilone N, Sheikh A, Sova M, Suppli Ulrik C, Taborda-Barata L, Todo-Bom A, Torres MJ, Tsiligianni I, Usmani OS, Valovirta E, Vasankari T, Vieira RJ, Wallace D, Waserman S, Zidarn M, Yorgancioglu A, Zhang L, Chivato T, Ollert Met al., 2023, Patient-centered digital biomarkers for allergic respiratory diseases and asthma: The ARIA-EAACI approach - ARIA-EAACI Task Force Report, ALLERGY, Vol: 78, Pages: 1758-1776, ISSN: 0105-4538

Journal article

Shamji MH, Ollert M, Adcock IM, Bennett O, Favaro A, Sarama R, Riggioni C, Annesi-Maesano I, Custovic A, Fontanella S, Traidl-Hoffmann C, Nadeau K, Cecchi L, Zemelka-Wiacek M, Akdis CA, Jutel M, Agache Iet 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, Vol: 78, Pages: 1742-1757, ISSN: 0105-4538

Allergic diseases and asthma are intrinsically linked to the environment we live in and to patterns of exposure. The integrated approach to understanding the effects of exposures on the immune system includes the ongoing collection of large-scale and complex data. This requires sophisticated methods to take full advantage of what this data can offer. Here we discuss the progress and further promise of applying artificial intelligence and machine-learning approaches to help unlock the power of complex environmental data sets toward providing causality models of exposure and intervention. We discuss a range of relevant machine-learning paradigms and models including the way such models are trained and validated together with examples of machine learning applied to allergic disease in the context of specific environmental exposures as well as attempts to tie these environmental data streams to the full representative exposome. We also discuss the promise of artificial intelligence in personalized medicine and the methodological approaches to healthcare with the final AI to improve public health.

Journal article

Krishna MT, Shamji MH, Boyle RJ, 2023, Allergy in India, CLINICAL AND EXPERIMENTAL ALLERGY, Vol: 53, Pages: 690-692, ISSN: 0954-7894

Journal article

de Kam PJ, Zielen S, Bernstein JA, Berger U, Berger M, Cuevas M, Cypcar D, Fuhr-Horst A, Greisner WA, Jandl M, Lassmann S, Worm M, Matz J, Sher E, Smith C, Steven GC, Moesges R, Shamji MH, DuBuske L, Borghese F, Oluwayi K, Zwingers T, Seybold M, Armfield O, Heath MD, Hewings SJ, Kramer MF, Skinner MAet al., 2023, Short-course subcutaneous treatment with PQ Grass strongly improves symptom and medication scores in grass allergy, ALLERGY, ISSN: 0105-4538

Journal article

Shamji MH, Boyle RJ, 2023, Novel diagnostics and therapeutic approaches for allergic diseases, CLINICAL AND EXPERIMENTAL ALLERGY, Vol: 53, Pages: 602-604, ISSN: 0954-7894

Journal article

Beirag N, Varghese PM, Neto MM, Al Aiyan A, Khan HA, Qablan M, Shamji MH, Sim RB, Temperton N, Kishore Uet al., 2023, Complement Activation-Independent Attenuation of SARS-CoV-2 Infection by C1q and C4b-Binding Protein., Viruses, Vol: 15

The complement system is a key component of the innate immune response to viruses and proinflammatory events. Exaggerated complement activation has been attributed to the induction of a cytokine storm in severe SARS-CoV-2 infection. However, there is also an argument for the protective role of complement proteins, given their local synthesis or activation at the site of viral infection. This study investigated the complement activation-independent role of C1q and C4b-binding protein (C4BP) against SARS-CoV-2 infection. The interactions of C1q, its recombinant globular heads, and C4BP with the SARS-CoV-2 spike and receptor binding domain (RBD) were examined using direct ELISA. In addition, RT-qPCR was used to evaluate the modulatory effect of these complement proteins on the SARS-CoV-2-mediated immune response. Cell binding and luciferase-based viral entry assays were utilised to assess the effects of C1q, its recombinant globular heads, and C4BP on SARS-CoV-2 cell entry. C1q and C4BP bound directly to SARS-CoV-2 pseudotype particles via the RBD domain of the spike protein. C1q via its globular heads and C4BP were found to reduce binding as well as viral transduction of SARS-CoV-2 spike protein expressing lentiviral pseudotypes into transfected A549 cells expressing human ACE2 and TMPRSS2. Furthermore, the treatment of the SARS-CoV-2 spike, envelope, nucleoprotein, and membrane protein expressing alphaviral pseudotypes with C1q, its recombinant globular heads, or C4BP triggered a reduction in mRNA levels of proinflammatory cytokines and chemokines such as IL-1β, IL-8, IL-6, TNF-α, IFN-α, and RANTES (as well as NF-κB) in A549 cells expressing human ACE2 and TMPRSS2. In addition, C1q and C4BP treatment also reduced SARS-CoV-2 pseudotype infection-mediated NF-κB activation in A549 cells expressing human ACE2 and TMPRSS2. C1q and C4BP are synthesised primarily by hepatocytes; however, they are also produced by macrophages, and alveolar type I

Journal article

Boyle RJ, Shamji MH, 2023, Food anaphylaxis in older people, CLINICAL AND EXPERIMENTAL ALLERGY, Vol: 53, Pages: 488-490, ISSN: 0954-7894

Journal article

Bousquet J, Melén E, Haahtela T, Koppelman GH, Togias A, Valenta R, Akdis CA, Czarlewski W, Rothenberg M, Valiulis A, Wickman M, Akdis M, Aguilar D, Bedbrook A, Bindslev-Jensen C, Bosnic-Anticevich S, Boulet LP, Brightling CE, Brussino L, Burte E, Bustamante M, Canonica GW, Cecchi L, Celedon JC, Chaves Loureiro C, Costa E, Cruz AA, Erhola M, Gemicioglu B, Fokkens WJ, Garcia-Aymerich J, Guerra S, Heinrich J, Ivancevich JC, Keil T, Klimek L, Kuna P, Kupczyk M, Kvedariene V, Larenas-Linnemann DE, Lemonnier N, Lodrup Carlsen KC, Louis R, Makela M, Makris M, Maurer M, Momas I, Morais-Almeida M, Mullol J, Naclerio RN, Nadeau K, Nadif R, Niedoszytko M, Okamoto Y, Ollert M, Papadopoulos NG, Passalacqua G, Patella V, Pawankar R, Pham-Thi N, Pfaar O, Regateiro FS, Ring J, Rouadi PW, Samolinski B, Sastre J, Savouré M, Scichilone N, Shamji MH, Sheikh A, Siroux V, Sousa-Pinto B, Standl M, Sunyer J, Taborda-Barata L, Toppila-Salmi S, Torres MJ, Tsiligianni I, Valovirta E, Vandenplas O, Ventura MT, Weiss S, Yorgancioglu A, Zhang L, Abdul Latiff AH, Aberer W, Agache I, Al-Ahmad M, Alobid I, Ansotegui IJ, Arshad SH, Asayag E, Barbara C, Baharudin A, Battur L, Bennoor KS, Berghea EC, Bergmann KC, Bernstein D, Bewick M, Blain H, Bonini M, Braido F, Buhl R, Bumbacea RS, Bush A, Calderon M, Calvo-Gil M, Camargos P, Caraballo L, Cardona V, Carr W, Carreiro-Martins P, Casale T, Cepeda Sarabia AM, Chandrasekharan R, Charpin D, Chen YZ, Cherrez-Ojeda I, Chivato T, Chkhartishvili E, Christoff G, Chu DK, Cingi C, Correia de Sousa J, Corrigan C, Custovic A, D'Amato G, Del Giacco S, De Blay F, Devillier P, Didier A, do Ceu Teixeira M, Dokic D, Douagui H, Doulaptsi M, Durham S, Dykewicz M, Eiwegger T, El-Sayed ZA, Emuzyte R, Fiocchi A, Fyhrquist N, Gomez RM, Gotua M, Guzman MA, Hagemann J, Hamamah S, Halken S, Halpin DMG, Hofmann M, Hossny E, Hrubiško M, Irani C, Ispayeva Z, Jares E, Jartti T, Jassem E, Julge K, Just J, Jutel M, Kaidashev I, Kalayci O, Kalyoncu AF, Kardas P, Kirenga B, Kraxner Het 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.

Journal article

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