Imperial College London
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ProfessorMohamedShamji

Faculty of Medicine, National 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

Citation

BibTex format

@article{Altman:2023:10.1016/j.jaci.2023.06.025,
author = {Altman, MC and Segnitz, RM and Larson, D and Jayavelu, ND and Smith, M and Patel, S and Scadding, GW and Qin, T and Sanda, S and Steveling, E and Eifan, AO and Penagos, M and Jacobson, MR and Parkin, RV and Shamji, MH and Togias, A and Durham, SR},
doi = {10.1016/j.jaci.2023.06.025},
journal = {Journal of Allergy and Clinical Immunology},
pages = {1247--1260},
title = {Nasal and blood transcriptomic pathways underpinning the clinical response to grass pollen immunotherapy},
url = {http://dx.doi.org/10.1016/j.jaci.2023.06.025},
volume = {152},
year = {2023}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - 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.
AU  - Altman,MC
AU  - Segnitz,RM
AU  - Larson,D
AU  - Jayavelu,ND
AU  - Smith,M
AU  - Patel,S
AU  - Scadding,GW
AU  - Qin,T
AU  - Sanda,S
AU  - Steveling,E
AU  - Eifan,AO
AU  - Penagos,M
AU  - Jacobson,MR
AU  - Parkin,RV
AU  - Shamji,MH
AU  - Togias,A
AU  - Durham,SR
DO  - 10.1016/j.jaci.2023.06.025
EP  - 1260
PY  - 2023///
SN  - 0091-6749
SP  - 1247
TI  - Nasal and blood transcriptomic pathways underpinning the clinical response to grass pollen immunotherapy
T2  - Journal of Allergy and Clinical Immunology
UR  - http://dx.doi.org/10.1016/j.jaci.2023.06.025
UR  - https://www.ncbi.nlm.nih.gov/pubmed/37460024
UR  - http://hdl.handle.net/10044/1/105650
VL  - 152
ER  -
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