Publications
358 results found
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
Qaseem AS, Singh I, Pathan AA, et al., 2017, A Recombinant Fragment of Human Surfactant Protein D Suppresses Basophil Activation, Th2 and B Cell Responses in Grass Pollen-induced Allergic Inflammation., American Journal of Respiratory and Critical Care Medicine, Vol: 196, Pages: 1526-1534, ISSN: 1073-449X
RATIONALE: rfhSP-D has been shown to suppress house dust mite and Aspergillus fumigatus-induced allergic inflammation in murine models. OBJECTIVES: We sought to elucidate the effect of rfhSP-D on FcεRI and CD23-mediated grass pollen induced allergic inflammatory responses. METHODS: rfhSP-D, containing homotrimeric neck and lectin domains, was expressed in Escherichia coli BL21 (λDE3) pLysS. PBMCs and sera were obtained from grass pollen allergic individuals (n=27). The effect of rfhSP-D on basophil activation and histamine release was measured by flow cytometry. IgE-facilitated allergen binding and presentation was assessed by flow cytometry. Th2 cytokines were measured in cell culture supernatants. The effect of rfhSP-D on IgE production by B cells when stimulated with CD40L, IL-4 and IL-21 was also determined. RESULTS: rfhSP-D bound to Phleum pratense in a dose- and calcium-dependent manner. Allergen-induced basophil responsiveness and histamine release was inhibited in the presence of rfhSP-D, as measured by CD63, CD203c (P=0.0086,P=0.04205), and intracellular-labelled DAO (P=0.0003,P=0.0148). The binding of allergen-IgE complexes to B cells was reduced by 51%(P=0.002) in the presence of rfhSP-D. This decrease was concomitant with reduction in CD23 expression on B cells (P<0.001). rfhSP-D suppressed allergen-driven CD27-CD4+CRTH2+ T cell proliferation (P<0.01), IL-4 and IL-5 levels (all,P<0.01). Moreover, rfhSP-D inhibited CD40L/IL-4 and IL-21-mediated IgE production(77.12%; P=0.02) by B cells. CONCLUSION: For the first time, we show that rfhSP-D inhibited allergen-induced basophil responses at a single cell, level and suppressed CD23-mediated facilitated allergen presentation and Th2 cytokine production. In addition, rfhSP-D inhibited IgE synthesis by B cells, which is also a novel observation.
Bahri R, Robb A, Shamji MH, et al., 2017, Mast cell activation test distinguishes between sensitisation and clinical reactivity with improved diagnostic characteristics compared to other diagnostic techniques including basophil activation, Congress of the European-Academy-of-Allergy-and-Clinical-Immunology, Publisher: WILEY, Pages: 139-140, ISSN: 0105-4538
Turner PJ, Robb A, Gibbs BF, et al., 2017, Peripheral basopenia during peanutinduced allergic reactions-a protective response?, Congress of the European-Academy-of-Allergy-and-Clinical-Immunology, Publisher: WILEY, Pages: 131-131, ISSN: 0105-4538
Durham S, Schwabe C, Robson R, et al., 2017, A randomized clinical trial of passive immunotherapy with single-dose anti-Fel d1 monoclonal antibodies REGN 1908-1909 in cat-induced rhinoconjunctivitis: exploratory efficacy endpoints, safety, and, Congress of the European-Academy-of-Allergy-and-Clinical-Immunology, Publisher: WILEY, Pages: 64-65, ISSN: 0105-4538
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- Citations: 5
Skypala IJ, Cecchi L, Shamji MH, et al., 2017, Lipid transfer protein allergy in UK adults-characterisation and comparison to adults with pollen-food syndrome, Congress of the European-Academy-of-Allergy-and-Clinical-Immunology, Publisher: WILEY, Pages: 29-29, ISSN: 0105-4538
Shamji MH, Mosges R, Bonny M, et al., 2017, Short course treatment of subcutaneous peptide hydrolysate from lolium perenne (LPP) suppresses basophil responses and induces igg-associated blocking antibodies: a RDPCT, Congress of the European-Academy-of-Allergy-and-Clinical-Immunology, Publisher: WILEY, Pages: 143-143, ISSN: 0105-4538
Moesges R, Panzner P, Pfaar O, et al., 2017, Efficacy of a 3-week subcutaneous immunotherapy course in patients with grass pollen-induced rhinoconjunctivitis: Results of a phase-3 study, Congress of the European-Academy-of-Allergy-and-Clinical-Immunology, Publisher: WILEY, Pages: 374-374, ISSN: 0105-4538
Kim EH, Sicherer SH, Wood RA, et al., 2017, Safety and tolerability of subcutaneous immunotherapy (SCIT) with a modified peanut extract in peanut-allergic adults, adolescents and children, Congress of the European-Academy-of-Allergy-and-Clinical-Immunology, Publisher: WILEY, Pages: 738-739, ISSN: 0105-4538
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- Citations: 1
Turner PJ, custovic A, Shamji MH, 2017, Basophils, high-affinity IgE receptors and CCL2 in human anaphylaxis, Journal of Allergy and Clinical Immunology, Vol: 140, Pages: 750-758.e15, ISSN: 1097-6825
Background: The role of basophils in anaphylaxis is unclear.Objective: Toinvestigatewhetherbasophils havean important rolein human anaphylaxis.Methods:In an emergency department study, we recruited 31 patientswith acute anaphylaxis,predominantly to hymenopteravenom. Wemeasuredexpression ofbasophilactivation markers(CD63, CD203c), the absolute number of circulating basophils, whole-bloodFcεRI, CPA3and HDCgene expression, and serum markers(CCL2, CCL5,CCL11, IL-3,TSLP)at threetime points(during the anaphylactic episode, and inconvalescent samples7and 30 days later). We recruited 134 hymenoptera-allergic and76healthy controlsfor comparison. Wetheninvestigated whether the changes observed during venom-related anaphylaxis also occur during allergic reactions to food in 22 peanut-allergic individuals undergoing double-blind placebo-controlled food challenge to peanut(DBPCFC).Results:The number of circulating basophils was significantly lower during anaphylaxis(median 3.5 cells/μl) than7and 30 days later(17.5 and 24.7 cells/μl, P<0.0001), and compared to venom-allergicand healthy controls (21and23.4 cells/μl,P<0.0001). FcεRIexpressionduring anaphylaxiswasalso significantly lower than in convalescent samples (P≤0.002) and venom-allergiccontrols(P<0.0001).CCL2 (but not other serum markers) wassignificantlyhigherduring anaphylaxis(median 658 pg/ml) than in convalescent samples (314and 311 pg/ml, 7 and 30days,P<0.001). Peanut-induced allergic reactions resulted in a significant decrease in circulating basophilscompared to pre-challenge samples(P=0.016), a decrease in FcεRI expression (P=0.007), and anincrease inCCL2(P=0.003).Conclusions: Our findings implyan important and specific role forbasophils in the pathophysiology of human anaphylaxis.
Kouser L, Kappen J, Walton RP, et al., 2017, Update on biomarkers to monitor clinical efficacy response during and post treatment in allergen immunotherapy, Curr Treat Options Allergy, Vol: 4, Pages: 43-53, ISSN: 2196-3053
Allergen immunotherapy (AIT) is an immune modulating treatment for allergic diseases. Although highly effective, some patients do not respond to the treatment. To date there are no surrogate biomarkers that are predictive of the clinical response to AIT. More and more is known about the underlying immunological mechanism involved in AIT. Through modulation of both innate and adaptive immune responses, involving reduced ILC2 and enhanced Treg and Breg induction and functionality, along with induction of IgG4 antibody production which have the capacity to inhibit both allergen-induced basophil responsiveness and CD23-mediated IgE-facilitated allergen presentation, the result is an immune skewing towards a more balanced Type I response. So far, however there is not a clear correlation with the observed immunological changes and predictive correlates of clinical efficacy. The most promising biomarker of successful AIT is IgE-FAB as a reflection of functional IgG4. Cellular responses and cytokine analysis gives a great deal of insight into the mechanisms of AIT but may not represent useful or indeed reliable biomarkers in a clinical setting. There is a need for more research for confirmation and interpretation of the possible association with biomarkers and clinical response to AIT.
Scadding GW, Calderon MA, Shamji MH, et al., 2017, Effect of 2 years of treatment with sublingual grass pollen immunotherapy on nasal response to allergen challenge at three years among patients with moderate to severe seasonal allergic rhinitis: The GRASS randomized clinical trial, Journal of the American Medical Association, Vol: 317, Pages: 615-625, ISSN: 0098-7484
Importance Sublingual immunotherapy and subcutaneous immunotherapy are effective in seasonal allergic rhinitis. Three years of continuous treatment with subcutaneous immunotherapy and sublingual immunotherapy has been shown to improve symptoms for at least 2 years following discontinuation of treatment.Objective To assess whether 2 years of treatment with grass pollen sublingual immunotherapy, compared with placebo, provides improved nasal response to allergen challenge at 3-year follow-up.Design, Setting, and Participants A randomized double-blind, placebo-controlled, 3–parallel-group study performed in a single academic center, Imperial College London, of adult patients with moderate to severe seasonal allergic rhinitis (interfering with usual daily activities or sleep). First enrollment was March 2011, last follow-up was February 2015.Interventions Thirty-six participants received 2 years of sublingual immunotherapy (daily tablets containing 15 µg of major allergen Phleum p 5 and monthly placebo injections), 36 received subcutaneous immunotherapy (monthly injections containing 20 µg of Phleum p 5 and daily placebo tablets) and 34 received matched double-placebo. Nasal allergen challenge was performed before treatment, at 1 and 2 years of treatment, and at 3 years (1 year after treatment discontinuation).Main Outcomes and Measures Total nasal symptom scores (TNSS; range; 0 [best] to 12 [worst]) were recorded between 0 and 10 hours after challenge. The minimum clinically important difference for change in TNSS within an individual is 1.08. The primary outcome was TNSS comparing sublingual immunotherapy vs placebo at year 3. Subcutaneous immunotherapy was included as a positive control. The study was not powered to compare sublingual immunotherapy with subcutaneous immunotherapy.Results Among 106 randomized participants (mean age, 33.5 years; 34 women [32.1%]), 92 completed the study at 3 years. In the intent-to-treat population, mean TNSS sc
Shamji MH, Kappen JH, Akdis M, et al., 2017, Biomarkers for monitoring clinical efficacy of allergen immunotherapy for allergic rhinoconjunctivitis and allergic asthma: an EAACI Position Paper, ALLERGY, Vol: 72, Pages: 1156-1173, ISSN: 0105-4538
Scadding G, Eifan AO, Calderon MA, et al., 2017, Response to Nasal Challenge Correlates with Seasonal Outcomes during Grass Pollen Immunotherapy with Either Subcutaneous or Sublingual Immunotherapy, Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology (AAAAI), Publisher: MOSBY-ELSEVIER, Pages: AB385-AB385, ISSN: 0091-6749
van Dijck AF, Kousar L, Layhadi J, et al., 2017, SATB1 is repressed in FoxP3+Tregs following Grass Pollen Subcutaneous and Sublingual Immunotherapy and Correlates with Clinical efficacy, Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology (AAAAI), Publisher: MOSBY-ELSEVIER, Pages: AB192-AB192, ISSN: 0091-6749
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- Citations: 2
Singh I, Qaseem A, Pathan A, et al., 2017, Surfactant Protein-D (SP-D): a Potential Therapeutic Target for Seasonal Allergic Rhinitis, Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology (AAAAI), Publisher: MOSBY-ELSEVIER, Pages: AB84-AB84, ISSN: 0091-6749
Pednekar L, Pathan AA, Paudyal B, et al., 2016, Analysis of the Interaction between Globular Head Modules of Human Cl q and Its Candidate Receptor gC1 qR, FRONTIERS IN IMMUNOLOGY, Vol: 7, ISSN: 1664-3224
Singh I, Qaseem AS, Pathan AA, et al., 2016, Surfactant protein D (SP-D): a novel therapeutic target for suppressing grass pollen-induced Th2 and B responses in seasonal allergic rhinitis, Annual Meeting of the British-Society-for-Allergy-and-Clinical-Immunology (BSACI), Publisher: WILEY-BLACKWELL, Pages: 1630-1630, ISSN: 0954-7894
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- Citations: 1
Scadding G, Calderon M, Shamji M, et al., 2016, Grass pollen subcutaneous and sublingual immunotherapy inhibit allergen-induced nasal and skin responses: a randomised controlled trial, Annual Meeting of the British-Society-for-Allergy-and-Clinical-Immunology (BSACI), Publisher: WILEY-BLACKWELL, Pages: 1639-1640, ISSN: 0954-7894
Calderon MA, Demoly P, Casale T, et al., 2016, Allergy immunotherapy across the life cycle to promote active and healthy ageing: from research to policies, Clinical and Translational Allergy, Vol: 6, ISSN: 2045-7022
Allergic diseases often occur early in life and persist throughout life. This life-course perspective should be considered in allergen immunotherapy. In particular it is essential to understand whether this al treatment may be used in old age adults. The current paper was developed by a working group of AIRWAYS integrated care pathways for airways diseases, the model of chronic respiratory diseases of the European Innovation Partnership on active and healthy ageing (DG CONNECT and DG Santé). It considered (1) the political background, (2) the rationale for allergen immunotherapy across the life cycle, (3) the unmet needs for the treatment, in particular in preschool children and old age adults, (4) the strategic framework and the practical approach to synergize current initiatives in allergen immunotherapy, its mechanisms and the concept of active and healthy ageing.
Slovick A, Douiri A, Muir R, et al., 2016, Intradermal grass pollen immunotherapy increases T(H)2 and IgE responses and worsens respiratory allergic symptoms, Journal of Allergy and Clinical Immunology, Vol: 139, Pages: 1830-1839.e13, ISSN: 0091-6749
BackgroundRepeated low-dose grass pollen intradermal allergen injection suppresses allergen-induced cutaneous late-phase responses comparably with conventional subcutaneous and sublingual immunotherapy.ObjectiveWe sought to evaluate the efficacy and safety of grass pollen intradermal immunotherapy in the treatment of allergic rhinitis.MethodsWe randomly assigned 93 adults with grass pollen–induced allergic rhinitis to receive 7 preseasonal intradermal allergen injections (containing 7 ng of Phl p 5 major allergen) or a histamine control. The primary end point was daily combined symptom-medication scores during the 2013 pollen season (area under the curve). Analysis was by intention to treat. Skin biopsy specimens were collected after intradermal allergen challenges, and late-phase responses were measured 4 and 7, 10, or 13 months after treatment.ResultsThere was no significant difference in the primary end point between treatment arms (active, n = 46; control, n = 47; median difference, 14; 95% CI, −172.5 to 215.1; P = .80). Among secondary end points, nasal symptoms were worse in the intradermal treatment group, as measured based on daily (median difference, 35; 95% CI, 4.0-67.5; P = .03) and visual analog scale (median difference, 53; 95% CI, −11.6 to 125.2; P = .05) scores. In a per-protocol analysis intradermal immunotherapy was further associated with worse asthma symptoms and fewer symptom-free days. Intradermal immunotherapy increased serum Phleum pratense–specific IgE levels (P = .001) compared with those in the control arm. T cells cultured from biopsy specimens of subjects undergoing intradermal immunotherapy had higher expression of the TH2 surface marker CRTH2 (P = .04) and lower expression of the TH1 marker CXCR3 (P = .01), respectively. Late-phase responses remained inhibited 7 months after treatment (P = .03).ConclusionIntradermal allergen immunotherapy suppressed skin late-phase responses but was not clinically effective and r
Kappen JH, Durham SR, Veen HI, et al., 2016, Applications and mechanisms of immunotherapy in allergic rhinitis and asthma., Therapeutic Advances in Respiratory Disease, Vol: 11, Pages: 73-86, ISSN: 1753-4658
Clinical and immunologic tolerance are hallmarks of successful allergen immunotherapy (AIT). Clinical benefits such as reduced symptoms, pharmacotherapy intake and improvement of quality of life persist following cessation of treatment. Successful AIT is associated with suppression of allergic inflammatory cells such as mast cells, eosinophils and basophils in target organs. Furthermore, AIT down-regulates type 2 innate lymphoid cells and allergen-specific type 2 T-helper (Th2) cells. The immunologic tolerant state following AIT is associated with the induction of distinct phenotypes of regulatory T-cells (T-regs) including interleukin (IL)-10-, IL-35- and transforming growth factor (TGF)-β- producing T-regs and FoxP3(+) T-regs. B-cell responses, including the induction of IL-10(+) regulatory B-cells (B-regs) and the production of IgG4-associated blocking antibodies are also induced following successful AIT. These events are associated with the suppression of antigen-specific Th2 responses and delayed immune deviation in favour of Th1 type responses. Insight into the mechanisms of AIT has allowed identification of novel biomarkers with potential to predict the clinical response to AIT and also novel therapeutic strategies for more effective and safer AIT.
Zadoyan G, Allekotte S, Shamji MH, et al., 2016, Immunological biomarker predict clinical effects in subcutaneous peptide allergen immunotherapy, Meeting of the European-Academy-of-Allergy-and-Clinical-Immunology, Publisher: WILEY-BLACKWELL, Pages: 319-320, ISSN: 0105-4538
Steveling-Klein EH, Lao-Araya M, Koulias C, et al., 2016, A randomised placebo-controlled trial of sublingual immunotherapy tablet for seasonal rhinitis to grass allergen: clinical outcomes, local symptoms and early time course of immunologic changes, Meeting of the European-Academy-of-Allergy-and-Clinical-Immunology, Publisher: WILEY-BLACKWELL, Pages: 616-616, ISSN: 0105-4538
Scadding G, Calderon M, Shamji MH, et al., 2016, Grass pollen subcutaneous and sublingual immunotherapy inhibit allergen-induced nasal responses and local Th2 cytokines: a randomised controlled trial, Meeting of the European-Academy-of-Allergy-and-Clinical-Immunology, Publisher: WILEY-BLACKWELL, Pages: 3-3, ISSN: 0105-4538
Scadding G, Calderon M, Shamji M, et al., 2016, Grass pollen subcutaneous immunotherapy results in faster and greater suppression of allergen-induced skin responses compared to sublingual immunotherapy: a randomised controlled trial, Meeting of the European-Academy-of-Allergy-and-Clinical-Immunology, Publisher: WILEY-BLACKWELL, Pages: 172-172, ISSN: 0105-4538
Kappen J, Schmidt-Weber C, Akdis M, et al., 2016, Evaluation of novel and current biomarkers for monitoring clinical efficacy of allergen immunotherapy for allergic rhinoconjunctivitis and allergic asthma, Meeting of the European-Academy-of-Allergy-and-Clinical-Immunology, Publisher: WILEY-BLACKWELL, Pages: 455-455, ISSN: 0105-4538
Varricchi G, Harker J, Borriello F, et al., 2016, T follicular helper (Tfh ) cells in normal immune responses and in allergic disorders., Allergy, Vol: 71, Pages: 1086-1094, ISSN: 0105-4538
Follicular helper T cells (Tfh ) are located within germinal centers of lymph nodes. Cognate interaction between Tfh , B cells, and IL-21 drives B cells to proliferate and differentiate into plasma cells thereby leading to antibody production. Tfh cells and IL-21 are involved in infectious and autoimmune diseases, immunodeficiencies, vaccination, and cancer. Human peripheral blood CXCR5(+) CD4(+) T cells comprise different subsets of Tfh -like cells. Despite the importance of the IgE response in the pathogenesis of allergic disorders, little is known about the role of follicular and blood Tfh cells and IL-21 in human and experimental allergic disease. Here, we review recent advances regarding the phenotypic and functional characteristics of both follicular and blood Tfh cells and of the IL-21/IL-21R system in the context of allergic disorders.
Ntavli E, Turner PJ, Boyle RJ, et al., 2016, Group 2 Innate Lymphoid Cells: New Players in Peanut Allergy, Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology (AAAAI), Publisher: MOSBY-ELSEVIER, Pages: AB74-AB74, ISSN: 0091-6749
Mohseni YR, Turner PJ, Boyle RJ, et al., 2016, Intracellular Expression of Fluorochrome Labelled-Diamine Oxidase in Basophils: A Novel Diagnostic Tool for Peanut Allergy, Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology (AAAAI), Publisher: MOSBY-ELSEVIER, Pages: AB137-AB137, ISSN: 0091-6749
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