100 results found
Scadding GK, Scadding GW, 2021, Innate and Adaptive Immunity: ILC2 and Th2 Cells in Upper and Lower Airway Allergic Diseases, JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE, Vol: 9, Pages: 1851-1857, ISSN: 2213-2198
Eifan A, Scadding G, Durham S, et al., 2021, Comparison of nasal allergen challenges with dissolved Timothy Grass pollen tablets and aqueous extract, Allergy, Vol: 76, Pages: 1543-1545, ISSN: 0105-4538
Shamji MH, Larson D, Eifan A, et al., 2021, Differential induction of allergen-specific IgA responses following timothy grass subcutaneous and sublingual immunotherapy., J Allergy Clin Immunol
INTRODUCTION: There is no detailed comparison of allergen-specific immunoglobulin responses following sublingual immunotherapy (SLIT) and subcutaneous immunotherapy (SCIT). OBJECTIVE: We sought to compare nasal and systemic timothy grass pollen (TGP)-specific antibody responses during 2 years of SCIT and SLIT and 1 year after treatment discontinuation in a double-blind, double-dummy, placebo-controlled trial. METHODS: Nasal fluid and serum were obtained yearly (per-protocol population, n = 84). TGP-specific IgA1, IgA2, IgG4, IgG, and IgE were measured in nasal fluids by ELISA. TGP-specific IgA1, IgA2, and Phleum pratense (Phl p)1, 2, 4, 5b, 6, 7, 11, and 12 IgE and IgG4 were measured in sera by ELISA and ImmunoCAP, respectively. RESULTS: At years 2 and 3, TGP-IgA1/2 levels in nasal fluid were elevated in SLIT compared with SCIT (4.2- and 3.0-fold for IgA1, 2.0- and 1.8-fold for IgA2, respectively; all P < .01). TGP-IgA1 level in serum was elevated in SLIT compared with SCIT at years 1, 2, and 3 (4.6-, 5.1-, and 4.7-fold, respectively; all P < .001). Serum TGP-IgG level was higher in SCIT compared with SLIT (2.8-fold) at year 2. Serum TGP-IgG4 level was higher in SCIT compared with SLIT at years 1, 2, and 3 (10.4-, 27.4-, and 5.1-fold, respectively; all P < .01). Serum IgG4 levels to Phl p1, 2, 5b, and 6 were increased at years 1, 2, and 3 in SCIT and SLIT compared with placebo (Phl p1: 11.8- and 3.9-fold; Phl p2: 31.6- and 4.4-fold; Phl p5b: 135.5- and 5.3-fold; Phl p6: 145.4- and 14.7-fold, respectively, all at year 2 when levels peaked; P < .05). IgE to TGP in nasal fluid increased in the SLIT group at year 2 but not at year 3 compared with SCIT (2.8-fold; P = .04) and placebo (3.1-fold; P = .02). IgA to TGP and IgE and IgG4 to TGP components stratified participants according to treatment group and clinical response. CONCLUSIONS: The observed induction of IgA1/2 in SLIT and IgG4 in SCIT suggest key differenc
Sharif H, Acharya S, Dhondalay GKR, et al., 2021, Altered chromatin landscape in circulating T follicular helper and regulatory cells following grass pollen subcutaneous and sublingual immunotherapy, Journal of Allergy and Clinical Immunology, Vol: 147, Pages: 663-676, ISSN: 0091-6749
BACKGROUND: Allergen-specific immunotherapy (AIT) is a disease-modifying treatment that induces long-term T cell tolerance. OBJECTIVE: To evaluate the role of circulating CXCR5+PD-1+T follicular helper (cTFH) and T follicular regulatory (TFR) cells following grass pollen subcutaneous (SCIT) and sublingual (SLIT) immunotherapy and the accompanying changes in their chromatin landscape. METHODS: Phenotype and function of cTFH cells were initially evaluated in grass pollen-allergics (GPA, n= 28) and non-atopic controls (NAC, n=13) by mathematical algorithms developed to manage high-dimensional data and cell culture, respectively. cTFH and TFR cells were further enumerated in NAC (n=12), GPA (n=14), SCIT (n=10) and SLIT (n=8)-treated groups. Chromatin accessibility in cTFH and TFR cells was assessed by ATAC-seq to investigate epigenetic mechanisms underlying the differences between NAC, GPA, SCIT and SLIT. RESULTS: cTFH cells were shown to be distinct from TH2 and TH2A cell subsets, capable of secreting IL-4 and IL-21. Both cytokines synergistically promoted B cell class switching to IgE and plasma cell differentiation. Grass pollen allergen induced cTFH cell proliferation in GPA but not in NAC (P<.05). cTFH cells were higher in GPA compared to NAC and were lower in SCIT and SLIT (P<.01). Time-dependent induction of IL-4, IL-21 and IL-6 were observed in nasal mucosa following intranasal allergen challenge in GPA but not in SCIT and SLIT groups. TFR and IL-10+ cTFH cells were induced in SCIT and SLIT (all, P<.01). ATAC-seq analyses revealed differentially accessible chromatin regions in all groups. CONCLUSION: For the first time, we showed dysregulation of cTFH cells in GPA compared to NAC, SCIT and SLIT and induction of TFR and IL-10+ cTFH cells following SCIT and SLIT. Changes in the chromatin landscape were observed following AIT in cTFH and TFR cells.
Parkin R, Laisuan W, Sanver D, et al., 2020, Evaluating a method validation to deplete, purify and determine the function of IgG4, IgA1 and IgA2 antibodies induced following sublingual immunotherapy in patients with allergic rhinitis, European-Academy-of-Allergology-and-Clinical-Immunology Digital Congress (EAACI), Publisher: WILEY, Pages: 131-131, ISSN: 0105-4538
Sharif H, Fear D, Laisuan W, et al., 2020, IL-10+T follicular helper cells (CXCR5+PD-1+CD4+TFH10) promote immune tolerance and regulate b cell function following allergen immunotherapy: A proof-of-concept cross-sectional study, European-Academy-of-Allergology-and-Clinical-Immunology Digital Congress (EAACI), Publisher: WILEY, Pages: 46-46, ISSN: 0105-4538
Larson D, Patel P, Salapatek AM, et al., 2020, Nasal allergen challenge and environmental exposure chamber challenge: A randomized trial comparing clinical and biological responses to cat allergen, JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, Vol: 145, Pages: 1585-1597, ISSN: 0091-6749
Marone G, Granata F, Pucino V, et al., 2019, The Intriguing Role of Interleukin 13 in the Pathophysiology of Asthma, FRONTIERS IN PHARMACOLOGY, Vol: 10, ISSN: 1663-9812
Vila-Nadal G, Gunawardana N, Rey-Garcia H, et al., 2019, Successful intravaginal graded human seminal plasma desensitization in a Can F5 sensitized patient, Congress of the European-Academy-of-Allergy-and-Clinical-Immunology (EAACI), Publisher: WILEY, Pages: 706-707, ISSN: 0105-4538
Garcia RH, Donovan J, Scadding G, et al., 2019, Is Pru p 3 a relevant test for lipid transfer protein allergy in a Northern European population?, Congress of the European-Academy-of-Allergy-and-Clinical-Immunology (EAACI), Publisher: WILEY, Pages: 142-142, ISSN: 0105-4538
Yi Y, Sharif H, Krasner-Macleod S, et al., 2019, Immunomodulation of CD4+CXCR5+PD-1+T follicular helper (Tfh) and CD4+CXCR5+PD-1+FoxP3+T follicular regulatory (Tfr) cell responses in grass pollen allergy, Congress of the European-Academy-of-Allergy-and-Clinical-Immunology (EAACI), Publisher: WILEY, Pages: 199-199, ISSN: 0105-4538
Lenormand M, Layhadi JA, Hu J, et al., 2019, Epigenetic changes in SATB1 gene in FoxP3+regulatory T cells reflect immune tolerance status during grass pollen subcutaneous and sublingual immunotherapy, Congress of the European-Academy-of-Allergy-and-Clinical-Immunology (EAACI), Publisher: WILEY, Pages: 63-64, ISSN: 0105-4538
Sharif H, Acharya S, Dhondalay GK, et al., 2019, Altered chromatin landscape in T follicular cells in seasonal allergic rhinitis and following allergen-specific immunotherapy, Congress of the European-Academy-of-Allergy-and-Clinical-Immunology (EAACI), Publisher: WILEY, Pages: 64-65, ISSN: 0105-4538
Hull JH, Walsted ES, Feary J, et al., 2019, Continuous laryngoscopy during provocation in the assessment of inducible laryngeal obstruction, Laryngoscope, Vol: 129, Pages: 1863-1866, ISSN: 0023-852X
Heffler E, Brussino L, Del Giacco S, et al., 2019, New drugs in early-stage clinical trials for allergic rhinitis, EXPERT OPINION ON INVESTIGATIONAL DRUGS, Vol: 28, Pages: 267-273, ISSN: 1354-3784
Shamji MH, Layhadi JA, Achkova D, et al., 2019, Role of interleukin-35 in sublingual allergy immunotherapy, Journal of Allergy and Clinical Immunology, Vol: 143, Pages: 1131-1142.e4, ISSN: 0091-6749
BACKGROUND: Grass pollen-specific immunotherapy involves immunomodulation of allergen-specific T helper 2 cell (Th2) responses and induction of IL-10+ and/or TGF-β+CD4+CD25+ regulatory T cells (iTregs). IL-35+CD4+CD25+Foxp3- T (iTR35) cells have been reported as a novel subset of iTregs with modulatory characteristics. OBJECTIVE: To investigate the mechanisms underlying the induction and maintenance of immunological tolerance induced by IL-35 and iTR35 cells. METHODS: The biological effects of IL-35 was assessed on Group II innate lymphoid cells (ILC2s), dendritic cells (DCs) primed with TSLP, IL-25 and IL-33, B and Th2 cells by flow cytometry and qRT-PCR. Grass pollen-driven Th2 cell proliferation and cytokine production was measured by [3H]-thymidine and Luminex MagPix, respectively. iTr35 cells were quantified in grass pollen allergics (SAR, n=16), sublingual immunotherapy-treated patients (SLIT, n=16) and non-atopic controls (NAC, n=16). RESULTS: SAR had elevated proportions of ILC2s (P=.002), IL5+ (P=.042), IL13+ (P=.042) and IL5+IL13+ILC2s (P=.003) compared to NAC. IL-35 inhibited IL-5 and IL-13 production by ILC2s in the presence of IL-25 or IL-33 (P=.031) and allergen-driven Th2 cytokines by Teff cells. IL-35 inhibited CD40L, IL-4 and IL-21-mediated IgE production by B cells (P=.015), allergen-driven T cell proliferation (P=.001) and Th2 cytokine production by primed DCs. iTR35 cells suppressed Th2 cell proliferation and cytokine production. In addition, allergen-driven IL-35 levels and iTR35 cells were elevated in SLIT (all, P<.001) and NAC (all, P<.001) compared to SAR. CONCLUSION: IL-35 and iTR35 cells are potential novel immune-regulators induced by SLIT. The clinical relevance of SLIT may be underscored by the restoration of protective iTR35 cells.
Muluk NB, Cingi C, Scadding GK, et al., 2019, Chronic Rhinosinusitis-Could Phenotyping or Endotyping Aid Therapy?, AMERICAN JOURNAL OF RHINOLOGY & ALLERGY, Vol: 33, Pages: 83-93, ISSN: 1945-8924
Garcia HR, Gunawardana N, Wheeler K, et al., 2018, Can component resolved diagnosis predict the outcome of oral food challenge to hazelnut?, Annual Meeting of the British-Society-for-Allergy-and-Clinical-Immunology (BSACI), Publisher: WILEY, Pages: 1547-1547, ISSN: 0954-7894
Layhadi JA, Achkova D, Kouser L, et al., 2018, Interleukin-35 regulates type II-mediated responses elicited by innate lymphoid cells in allergic diseases, Annual Meeting of the British-Society-for-Allergy-and-Clinical-Immunology (BSACI), Publisher: WILEY, Pages: 1548-1549, ISSN: 0954-7894
Layhadi J, Hu J, van Dijck A, et al., 2018, SATB1 expression and methylation reflect FOXP3(+) regulatory T cell activity during grass pollen immunotherapy, Annual Meeting of the British-Society-for-Allergy-and-Clinical-Immunology (BSACI), Publisher: WILEY, Pages: 1549-1549, ISSN: 0954-7894
Penagos M, Eifan AO, Durham SR, et al., 2018, Duration of allergen immunotherapy for long-term efficacy in allergic rhinoconjunctivitis, Current Treatment Options in Allergy, Vol: 5, Pages: 275-290, ISSN: 2196-3053
RationaleSubcutaneous and sublingual immunotherapy are effective for allergic rhinitis. An important question is whether allergen immunotherapy provides a sustained clinical effect after treatment cessation. In view of potential side effects, cost and the necessary patient commitment, long-term benefit is an important consideration for the recommendation of immunotherapy over standard pharmacotherapy.Purpose of reviewIn this review, we analyse the existing evidence for long-term effects of both routes of administration in the context of double-blind, placebo-controlled, randomised clinical trials that included a follow-up phase of at least 1 year after treatment cessation.Recent findingsOverall, evidence suggests that 3 years of either subcutaneous or sublingual immunotherapy result in clinical benefit and immunological changes consistent with allergen-specific tolerance sustained for at least 2–3 years after treatment cessation.SummaryThe data presented here support recommendations in international guidelines that both routes of administration should be continued for a minimum of 3 years. Gaps in the evidence remain regarding the long-term efficacy of immunotherapy for perennial rhinitis and studies performed in children.
Layhadi JA, Matsuoka T, Scadding G, et al., 2018, Interleukin (IL)-35 producing T regulatory cells (iTR35) suppresses type II innate lymphoid cell (ILC2) and T helper 2 (Th2) cell function and are induced following grass pollen immunotherapy, Congress of the European-Academy-of-Allergy-and-Clinical-Immunology (EAACI), Publisher: WILEY, Pages: 43-43, ISSN: 0105-4538
Rey-Garcia H, Gunawardana N, Wheeler K, et al., 2018, The predictive value of allergy tests in the diagnosis of peanut allergy in adults, Congress of the European-Academy-of-Allergy-and-Clinical-Immunology (EAACI), Publisher: WILEY, Pages: 422-422, ISSN: 0105-4538
Renand A, Shamji MH, Harris KM, et al., 2018, Synchronous immune alterations mirror clinical response during allergen immunotherapy, Journal of Allergy and Clinical Immunology, Vol: 141, Pages: 1750-1760.e1, ISSN: 0091-6749
BACKGROUND: Three years treatment with either sublingual or subcutaneous allergen immunotherapy has been shown to be effective and to induce long-term tolerance. The GRASS∗ trial demonstrated that two years treatment via either route was effective in suppressing the response to nasal allergen challenge, although was insufficient for inhibition one year after discontinuation. OBJECTIVE: To examine in the GRASS trial the time-course of immunologic changes during two years sublingual and subcutaneous immunotherapy and for one year after treatment discontinuation. METHODS: We performed multi-modal immunomonitoring to assess allergen-specific CD4 T cell properties, in parallel with analysis of local mucosal cytokine responses induced by nasal allergen exposure and humoral immune responses that included IgE-dependent basophil activation and measurement of serum inhibitory activity for allergen-IgE binding to B cells (IgE-Facilitated Allergen Binding). RESULTS: All three of these distinct arms of the immune response displayed significant and coordinate alterations during 2 years allergen desensitization, followed by reversal at 3 years, reflecting a lack of a durable immunological effect. Whereas frequencies of antigen-specific Th2 cells in peripheral blood determined by HLA class II tetramer analysis most closely paralleled clinical outcomes, IgE-antibody dependent functional assays remained partially inhibited one year following discontinuation. CONCLUSION: Two years of allergen immunotherapy were effective but insufficient for long-term tolerance. Allergen-specific Th2 cells most closely paralleled the transient clinical outcome and it is likely that recurrence of the T cell 'drivers' of allergic immunity abrogated the potential for durable tolerance. On the other hand, persistence of IgE-blocking antibody one year after discontinuation may be an early indicator of a pro-tolerogenic mechanism.
Fedina A, Scadding G, Durham S, 2017, Patient experiences of clinical research participation survey, Annual Meeting of the British-Society-for-Allergy-and-Clinical-Immunology (BSACI), Publisher: WILEY, Pages: 1715-1715, ISSN: 0954-7894
Gunawardana N, Matthews D, Rey-Garcia H, et al., 2017, Adherence to BSACI guidance on drug allergy testing at a UK allergy centre, Annual Meeting of the British-Society-for-Allergy-and-Clinical-Immunology (BSACI), Publisher: WILEY, Pages: 1687-1687, ISSN: 0954-7894
Eifan A, Scadding G, Calderon M, et al., 2017, Relationship between response to grass pollen nasal allergen challenge and seasonal symptoms and the effect of treatment compliance, Annual Meeting of the British-Society-for-Allergy-and-Clinical-Immunology (BSACI), Publisher: WILEY, Pages: 1686-1687, ISSN: 0954-7894
Selby J, Cullinan P, Feary J, et al., 2017, FEASIBILITY OF CONTINUOUS LARYNGOSCOPY DURING PROVOCATION IN THE ASSESSMENT OF INDUCIBLE LARYNGEAL OBSTRUCTION, Winter Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A143-A143, ISSN: 0040-6376
Garcia HR, Gunawardana N, Scadding G, et al., 2017, The value of allergy tests in predicting the outcome of oral food challenges to peanuts and tree nuts in adults, Annual Meeting of the British-Society-for-Allergy-and-Clinical-Immunology (BSACI), Publisher: WILEY, Pages: 1718-1718, ISSN: 0954-7894
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