1. Nasal and blood transcriptomic pathways underpinning the clinical response to grass pollen immunotherapy
- Author
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Altman, Matthew C, Segnitz, R Max, Larson, David, Jayavelu, Naresh Doni, Smith, Malisa T, Patel, Sana, Scadding, Guy W, Qin, Tielin, Sanda, Srinath, Steveling, Esther, Eifan, Aarif O, Penagos, Martin, Jacobson, Mikila R, Parkin, Rebecca V, Shamji, Mohamed H, Togias, Alkis, and Durham, Stephen R
- Subjects
Biomedical and Clinical Sciences ,Clinical Sciences ,Clinical Trials and Supportive Activities ,Clinical Research ,Human Genome ,Genetics ,Allergic Rhinitis (Hay Fever) ,Lung ,5.1 Pharmaceuticals ,Inflammatory and immune system ,Humans ,Transcriptome ,Leukocytes ,Mononuclear ,Pollen ,Allergens ,Desensitization ,Immunologic ,Sublingual Immunotherapy ,Phleum ,Injections ,Subcutaneous ,Rhinitis ,Allergic ,Allergen immunotherapy ,sublingual immunotherapy ,subcutaneous immunotherapy ,RNA sequencing ,allergic rhinitis ,Immunology ,Allergy - Abstract
BackgroundAllergen immunotherapy (AIT) is a well-established disease-modifying therapy for allergic rhinitis, yet the fundamental mechanisms underlying its clinical effect remain inadequately understood. Gauging Response in Allergic Rhinitis to Sublingual and Subcutaneous Immunotherapy was a randomized, double-blind, placebo-controlled trial of individuals allergic to timothy grass who received 2 years of placebo (n = 30), subcutaneous immunotherapy (SCIT) (n = 27), or sublingual immunotherapy (SLIT) (n = 27) and were then followed for 1 additional year.ObjectiveWe used yearly biospecimens from the Gauging Response in Allergic Rhinitis to Sublingual and Subcutaneous Immunotherapy study to identify molecular mechanisms of response.MethodsWe used longitudinal transcriptomic profiling of nasal brush and PBMC samples after allergen provocation to uncover airway and systemic expression pathways mediating responsiveness to AIT.Trial registrationClinicalTrials.gov Identifier: NCT01335139, EudraCT Number: 2010-023536-16.ResultsSCIT 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 -0.133 to -0.640, false discovery rates [FDRs]
- Published
- 2023