Publications
358 results found
Shamji MH, Kappen J, Abubakar-Waziri H, et al., 2019, Nasal allergen neutralising IgG4 antibodies block IgE-mediated responses: novel biomarker of subcutaneous grass pollen immunotherapy, Journal of Allergy and Clinical Immunology, Vol: 143, Pages: 1067-1076, ISSN: 0091-6749
BACKGROUND: Grass pollen subcutaneous immunotherapy (SCIT) is associated with induction of serum IgG4-associated inhibitory antibodies that prevent IgE-facilitated allergen binding to B cells. OBJECTIVE: To determine whether SCIT induces nasal allergen-specific IgG4 antibodies with inhibitory activity that correlate closely with clinical response. METHODS: In a cross-sectional, controlled study, nasal fluid and sera were collected during the grass pollen season from 10 SCIT-treated patients, 13 untreated allergics (SAR) and 12 non-atopic controls (NA). Nasal and serum IgE and IgG4 to Phleum pratense (Phl p) components were measured by ISAC microarray. Inhibitory activity was measured by IgE-FAB assay. IL-10+Breg cells were quantified in peripheral blood by flow cytometry. RESULTS: Nasal and serum Phl p1 and Phl p5-specific IgE levels were elevated in SAR compared to NA (all, P < .001) and SCIT group. Nasal IgG4 levels were increased in SCIT compared to SAR group (P < .001) during the pollen season compared to out of season. IgG-associated inhibitory activity in nasal fluid and serum was significantly increased in SCIT compared to SAR group (both, P < .001). The magnitude of the inhibitory activity was 96% in the nasal fluid compared to 66% in serum and was reversed following depletion of IgG in nasal fluid (P = .03) and serum (P = .002). Both nasal fluid (r = -0.67, P = .0011) and serum (r = -0.59, P = .0097) blocking activity correlated global symptom improvement. IL-10+Breg cells were increased in season compared to out of season in SCIT group (P < .01). CONCLUSION: For the first time, we show that nasal IgG4-associated inhibitory activity correlate closely with the clinical response to allergen immunotherapy in allergic rhinitis with/without asthma.
Layhadi JA, Eguiluz-Gracia I, Shamji MH, 2019, Role of IL-35 in sublingual allergen immunotherapy, Current Opinion in Allergy and Clinical Immunology, Vol: 19, Pages: 12-17, ISSN: 1473-6322
PURPOSE OF REVIEW: Sublingual allergen immunotherapy (SLIT), a disease-modifying treatment for allergic rhinitis, can induce long-term clinical benefits which are mediated by immune responses that include generation of regulatory B (Breg) and T (Treg) cells. The newest member of the IL-12 superfamily, IL-35, is an anti-inflammatory cytokine known to be produced by Breg and Treg cells. Limited studies are available on the role of IL-35 on allergic rhinitis and during SLIT. This review summarizes recent findings relevant to the topic of IL-35 and their role in SLIT. RECENT FINDINGS: Recombinant IL-35 protein can induce the generation of IL-35-producing Breg and Treg cells with immunosuppressive capacity. Levels of IL-35 and IL-35-inducible Treg (iTR35) cells are dysregulated in allergic rhinitis patients, which can be restored with SLIT. Mechanism of IL-35-mediated tolerance to allergens includes suppressions of T cell proliferation, Th2 cytokine production, and B cell production of IgE antibodies. SUMMARY: Emerging evidence supports a potential role for IL-35 and iTR35 cells in tolerance maintenance during SLIT. A better understanding for the role of IL-35 and iTR35 cells could provide new avenues for the development of clinical biomarker to assess efficacy of allergen immunotherapy and novel therapeutic strategies for allergic rhinitis.
Patel N, Vazquez-Ortiz M, Robb A, et al., 2019, Successful Desensitisation And Sustained Unresponsiveness Using Modified Peanut: Results From The BOPI Study, Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology (AAAAI), Publisher: MOSBY-ELSEVIER, Pages: AB83-AB83, ISSN: 0091-6749
Campo P, Eguiluz-Gracia I, Bogas G, et al., 2019, Local allergic rhinitis: Implications for management, Clinical and Experimental Allergy, Vol: 49, Pages: 6-16, ISSN: 0954-7894
A significant proportion of rhinitis patients without systemic IgE-sensitisation tested by skin prick test and serum allergen-specific IgE (sIgE) display nasal reactivity upon nasal allergen provocation test (NAPT). This disease phenotype has been termed local allergic rhinitis (LAR). LAR is an underdiagnosed entity affecting children and adults from different parts of the world, with moderate-to-severe symptoms, impairment of quality of life and rapid progression to symptom worsening. LAR is a stable phenotype and not merely an initial state of AR. Allergic rhinitis and LAR share many clinical features including a positive NAPT response, markers of type 2 nasal inflammation including sIgE in nasal secretions and a significant rate of asthma development. LAR should be considered as a differential diagnosis in those subjects of any age with symptoms suggestive of AR but no evidence of systemic atopy. Although LAR pathophysiology is partially unknown, in some patients sIgE can be demonstrated directly in the nasal secretions and/or indirectly via positive responses in basophil activation test (BAT). LAR can coexist with other rhinitis phenotypes, especially AR. The diagnosis currently relies on the positivity of NAPT to a single or multiple allergens. NAPT has high sensitivity, specificity and reproducibility, and it is considered the gold standard. BAT and the measurement of nasal sIgE can also contribute to LAR diagnosis. LAR patients benefit from the same therapeutic strategies than AR individuals, including the avoidance of allergen exposure and the pharmacotherapy. Moreover, several recent studies support the effectiveness and safety of allergen immunotherapy for LAR, which opens a window of treatment opportunity in these patients.
Ntavli E, Sahiner UM, Layhadi J, et al., 2018, Group 2 innate lymphoid cells (ILC2s) contribute to the pathophysiology of Peanut Allergy, Annual Meeting of the British-Society-for-Allergy-and-Clinical-Immunology (BSACI), Publisher: WILEY, Pages: 1528-1528, ISSN: 0954-7894
Kirtland M, Tsitoura D, Durham S, et al., 2018, An in vitro assay to screen Toll-like Receptor agonists as potential adjuvants in allergen immunotherapy, Annual Meeting of the British-Society-for-Allergy-and-Clinical-Immunology (BSACI), Publisher: WILEY, Pages: 1527-1527, ISSN: 0954-7894
Hug O, Singh I, Robb A, et al., 2018, IL-35 induces IL-10 producing Regulatory B cells in immunotherapy treated patients, Annual Meeting of the British-Society-for-Allergy-and-Clinical-Immunology (BSACI), Publisher: WILEY, Pages: 1548-1548, 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
Tang J, Singh I, Parkin R, et al., 2018, Clinical and immunologic effects of a single dose of Anti-Fel d 1-IgG4 monoclonal antibodies in cat allergic individuals: a double blind randomized placebo-controlled study, Annual Meeting of the British-Society-for-Allergy-and-Clinical-Immunology (BSACI), Publisher: WILEY, Pages: 1528-1528, ISSN: 0954-7894
Layhadi J, Hu J, van Dijck A, et al., 2018, SATB1 expression and methylation reflect FOXP3<SUP>+</SUP> 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
Patel K, Vila-Nadal G, Shah J, et al., 2018, The prevalence of pollen food syndrome in adults with irritable bowel syndrome, Annual Meeting of the British-Society-for-Allergy-and-Clinical-Immunology (BSACI), Publisher: WILEY, Pages: 1537-1538, ISSN: 0954-7894
Rondón C, Eguíluz-Gracia I, Shamji MH, et al., 2018, IgE test in secretions of patients with respiratory allergy, Current Allergy and Asthma Reports, Vol: 18, ISSN: 1529-7322
PURPOSE OF REVIEW: IgE is a key player in multiple inflammatory airway diseases. Ample literature demonstrates its presence in mucosa of patients with allergic rhinitis (AR), local allergic rhinitis (LAR), asthma, or chronic rhinosinusitis with nasal polyposis (CRSwNP). RECENT FINDINGS: Current evidence shows that high-affinity IgE in blood stream of allergic individuals derives mainly from the mucosae. Also, mucosal synthesis of IgE can occur in the absence of systemic atopy, and may be relevant in atopic and non-atopic phenotypes of rhinitis as demonstrated in LAR. Specific IgE (sIgE) detection varies depending on technique used for sample collection and its measurement. sIgE detection is highly specific for diagnosis of LAR. Moreover, measurement of sIgE in secretions could be useful in monitoring response to allergen-specific immunotherapy in both AR and LAR phenotypes. This review will focus on recent developments in the role of IgE in respiratory diseases, and the clinical implications of its measurement in secretions.
Shamji MH, Ceuppens J, Bachert C, et al., 2018, Lolium perenne peptides for treatment of grass pollen allergy: a randomized, double-blind, placebo-controlled clinical trial, Journal of Allergy and Clinical Immunology, Vol: 141, Pages: 448-+, ISSN: 0091-6749
Jakwerth CA, Shamji MH, Kappen JH, et al., 2018, Biomarkers for monitoring clinical efficacy of allergen immunotherapy for allergic rhinoconjunctivitis and allergic asthma: an EAACI Position Paper, ALLERGOLOGIE, Vol: 41, Pages: 376-385, ISSN: 0344-5062
Mösges R, Bachert C, Panzner P, et al., 2018, Short-course of grass allergen peptides immunotherapy over three weeks reduces seasonal symptoms in allergic rhinoconjunctivitis with/without Asthma: A randomized, multicenter, double-blind, placebo-controlled trial, Allergy, Vol: 73, Pages: 1842-1850, ISSN: 0105-4538
BACKGROUND: Immunotherapy with peptide hydrolysates from Lolium perenne (LPP) is an alternative treatment for seasonal allergic rhinitis with or without asthma. The aim of this study was to assess the clinical efficacy and safety of a cumulative dose of 170 μg LPP administered subcutaneously over 3 weeks. METHODS: In a randomized, double blind, placebo-controlled trial, 554 adults with grass pollen rhinoconjunctivitis were randomized (1:2 ratio) to receive 8 subcutaneous injections of placebo or 170 μg LPP administered in increasing doses in 4 visits over 3 weeks. The primary outcome was the combined symptom and medication score (CSMS) measured over the peak pollen season. Reactivity to conjunctival provocation test (CPT) and quality of life (QOL) were assessed as secondary endpoints. RESULTS: The mean reduction in CSMS in the LPP vs. placebo group was -15.5% (p=0.041) during the peak period and -17.9% (p= 0.029) over the entire pollen season. LPP treated group had a reduced reactivity to CPT (p<0.001) and, during the pollen season, a lower rhinoconjunctivitis QOL global score (p=0.005) compared to placebo group. Mostly mild and WAO grade 1 early systemic reaction (ESR) were observed ≤ 30 min in 10.5% of LPP-treated patients, whereas 3 patients with a medical history of asthma (<1%) experienced a serious ESR that resolved with rescue medication. CONCLUSION: LPP administered over 3 weeks before the grass pollen season significantly reduced seasonal symptoms, was generally safe and well-tolerated This article is protected by copyright. All rights reserved.
Bulfone-Paus S, Bahri R, Shamji MH, et al., 2018, Mast cell activation test versus basophil activation test and related competing issues Reply, JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, Vol: 142, Pages: 1019-1019, ISSN: 0091-6749
Shamji MH, Temblay JN, Cheng W, et al., 2018, Antiapoptotic serine protease inhibitors contribute to survival of allergenic TH2 cells, Journal of Allergy and Clinical Immunology, Vol: 142, Pages: 569-581.e5, ISSN: 0091-6749
BACKGROUND: The mechanisms that regulate maintenance of persistent TH2 cells and potentiate allergic inflammation are not well understood. OBJECTIVE: The function of serine protease inhibitor 2A (Spi2A) was studied in mouse TH2 cells, and the serine protease inhibitor B3 (SERPINB3) and SERPINB4 genes were studied in TH2 cells from patients with grass pollen allergy. METHODS: Spi2A-deficient TH2 cells were studied in in vitro culture or in vivo after challenge of Spi2A knockout mice with ovalbumin in alum. Expression of SERPINB3 and SERPINB4 mRNA was measured in in vitro-cultured TH2 cells and in ex vivo CD27-CD4+ cells and innate lymphoid cell (ILC) 2 from patients with grass pollen allergy by using quantitative PCR. SERPINB3 and SERPINB4 mRNA levels were knocked down in cultured CD27-CD4+ cells with small hairpin RNA. RESULTS: There were lower levels of in vitro-polarized TH2 cells from Spi2A knockout mice (P < .005) and in vivo after ovalbumin challenge (P < .05), higher levels of apoptosis (Annexin V positivity, P < .005), and less lung allergic inflammation (number of lung eosinophils, P < .005). In vitro-polarized TH2 cells from patients with grass pollen allergy expressed higher levels of both SERPINB3 and SERPINB4 mRNA (both P < .05) compared with unpolarized CD4 T cells. CD27-CD4+ from patients with grass pollen allergy expressed higher levels of both SERPINB3 and SERPINB4 mRNA (both P < .0005) compared with CD27+CD4+ cells. ILC2 expressed higher levels of both SERPINB3 and SERPINB4 mRNA (both P < .0005) compared with ILC1. Knockdown of either SERPINB3 or SERPINB4 mRNA (both P < .005) levels resulted in decreased viability of CD27-CD4+ compared with control transduced cells. CONCLUSION: The Serpins Spi2A in mice and SERPINB3 and SERPINB4 in allergic patients control the viability of TH2 cells. This provides proof of princ
Bahri R, Custovic A, Korosec P, et al., 2018, Mast cell activation test in the diagnosis of allergic disease and anaphylaxis, Journal of Allergy and Clinical Immunology, Vol: 142, Pages: 485-496.e16, ISSN: 0091-6749
BackgroundFood allergy is an increasing public health issue and the most common cause of life-threatening anaphylactic reactions. Conventional allergy tests assess for the presence of allergen-specific IgE, significantly overestimating the rate of true clinical allergy and resulting in overdiagnosis and adverse effect on health-related quality of life.ObjectiveTo undertake initial validation and assessment of a novel diagnostic tool, we used the mast cell activation test (MAT).MethodsPrimary human blood-derived mast cells (MCs) were generated from peripheral blood precursors, sensitized with patients' sera, and then incubated with allergen. MC degranulation was assessed by means of flow cytometry and mediator release. We compared the diagnostic performance of MATs with that of existing diagnostic tools to assess in a cohort of peanut-sensitized subjects undergoing double-blind, placebo-controlled challenge.ResultsHuman blood-derived MCs sensitized with sera from patients with peanut, grass pollen, and Hymenoptera (wasp venom) allergy demonstrated allergen-specific and dose-dependent degranulation, as determined based on both expression of surface activation markers (CD63 and CD107a) and functional assays (prostaglandin D2 and β-hexosaminidase release). In this cohort of peanut-sensitized subjects, the MAT was found to have superior discrimination performance compared with other testing modalities, including component-resolved diagnostics and basophil activation tests. Using functional principle component analysis, we identified 5 clusters or patterns of reactivity in the resulting dose-response curves, which at preliminary analysis corresponded to the reaction phenotypes seen at challenge.ConclusionThe MAT is a robust tool that can confer superior diagnostic performance compared with existing allergy diagnostics and might be useful to explore differences in effector cell function between basophils and MCs during allergic reactions.
Stranzl T, Lundegaard C, Ohashi-Doi K, et al., 2018, A machine learning approach to evaluate IgE and IgG4 responses as patient-specific measure of exposure to sublingual allergen immunotherapy, Congress of the European-Academy-of-Allergy-and-Clinical-Immunology (EAACI), Publisher: WILEY, Pages: 336-337, ISSN: 0105-4538
Moesges R, Demoly P, Lehmacher W, et al., 2018, Safety of a 3-week allergen immunotherapy course with grass pollen peptides: A randomised double-blind placebo-controlled trial, Congress of the European-Academy-of-Allergy-and-Clinical-Immunology (EAACI), Publisher: WILEY, Pages: 471-471, ISSN: 0105-4538
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
Mösges R, Koch AF, Raskopf E, et al., 2018, Lolium perenne peptide immunotherapy is well tolerated and elicits a protective B-cell response in seasonal allergic rhinitis patients, Allergy, Vol: 73, Pages: 1254-1262, ISSN: 0105-4538
BACKGROUND: Systemic allergic reactions are a risk for allergen immunotherapy that utilizes intact allergen preparations. We evaluated the safety, efficacy and immune mechanisms of short-course treatment with adjuvant-free Lolium perenne peptides (LPP) following a 6-week dose-escalation protocol. METHODS: In a prospective, dose-escalation study, 61 grass pollen-allergic patients received 2 subcutaneous injections of LPP once weekly for 6 weeks. Safety was assessed evaluating local reactions, systemic reactions and adverse events. The clinical effect of LPP was determined by reactivity to the conjunctival provocation test (CPT). Specific IgE, IgG4and blocking antibodies were measured at baseline (V1), during (V6) and after treatment (V8). RESULTS: No fatality, serious adverse event or epinephrine use was reported. Mean wheal diameters after injections were <0.6 cm and mean redness diameters <2.5 cm, independent of dose. Transient and mostly mild adverse events were reported in 33 patients. Two patients experienced a grade I and 4 patients a grade II reaction (AWMF classification). At V8, 69.8% of patients became nonreactive to CPT. sIgG4levels were higher at V6 (8.1-fold, P < .001) and V8 (12.2-fold, P < .001) than at V1. The sIgE:sIgG4ratio decreased at V6 (-54.6%, P < .001) and V8 (-71.6%, P < .001) compared to V1. The absolute decrease in IgE-facilitated allergen binding was 18% (P < .001) at V6 and 25% (P < .001) at V8. CONCLUSION: Increasing doses of subcutaneous LPP appeared safe, substantially diminished reactivity to CPT and induced blocking antibodies as early as 4 weeks after treatment initiation. The benefit/risk balance of LPP immunotherapy remains to be further evaluated in large studies.
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.
Krohn IK, Shikhagaie MM, Golebski K, et al., 2018, Emerging roles of innate lymphoid cells in inflammatory diseases: Clinical implications, ALLERGY, Vol: 73, Pages: 837-850, ISSN: 0105-4538
- Author Web Link
- Cite
- Citations: 66
Mosges R, Bachert C, Creticos PS, et al., 2018, Quality of Life during the hay fever season after short-course subcutaneous immunotherapy with Lolium perenne peptides (LPP) in grass pollen related rhinoconjunctivitis: A RDBPCT, American-Academy-of-Allergy-Asthma-and-Immunology / World-Allergy-Organization Joint Congress, Publisher: MOSBY-ELSEVIER, Pages: AB291-AB291, ISSN: 0091-6749
Sharif H, Karamani A, Parkin R, et al., 2018, Short Course of Lolium Perenne Peptides (LPP) Immunotherapy Deletes Circulating IL-4<SUP>+</SUP>IL-21<SUP>+</SUP> T follicular helper cells and Induces FoxP3<SUP>+</SUP> T follicular regulatory cells: A Randomized Controlled Trial, American-Academy-of-Allergy-Asthma-and-Immunology / World-Allergy-Organization Joint Congress, Publisher: MOSBY-ELSEVIER, Pages: AB197-AB197, ISSN: 0091-6749
Singh I, Sharif H, Kouser L, et al., 2018, Short Course of <i>Lolium Perenne</i> Peptides (LPP) Immunotherapy Induces IL-35<SUP>+</SUP> T Regulatory Cells (iTr35) that Promote B Regulatory Cells (Bregs) and Blocking Antibodies, American-Academy-of-Allergy-Asthma-and-Immunology / World-Allergy-Organization Joint Congress, Publisher: MOSBY-ELSEVIER, Pages: AB122-AB122, ISSN: 0091-6749
Pfaar O, Bonini S, Cardona V, et al., 2018, Perspectives in allergen immunotherapy: 2017 and beyond, Allergy, Vol: 73, Pages: 5-23, ISSN: 0105-4538
The Future of the Allergists and Specific Immunotherapy (FASIT) workshop provides a regular platform for global experts from academia, allergy clinics, regulatory authorities and industry to review developments in the field of allergen immunotherapy (AIT). The most recent meeting, held in February 2017, had two main themes: advances in AIT and hot topics in AIT from the regulatory point of view. The first theme covered opportunities for personalized AIT, advances in adjuvants and delivery systems, and the development of new molecules and future vaccines for AIT. Key topics in the second part of the meeting were the effects of the enactment of European Directive 2001/83 on the availability of allergens for therapy and diagnosis across the EU, the challenges of conducting Phase 3 studies in the field, the future role of allergen exposure chambers in AIT studies and specific considerations in performing AIT studies in the paediatric population. Finally, the group highlighted the forthcoming EAACI guidelines and their particular importance for the standardization of practice in the treatment of allergies. This review presents a comprehensive insight into those panel discussions and highlights unmet needs and also possible solutions to them for the future.
Mösges R, Kasche EM, Raskopf E, et al., 2017, A randomized, double-blind, placebo-controlled, dose-finding trial with Lolium perenne peptide immunotherapy, Allergy, Vol: 73, Pages: 896-904, ISSN: 0105-4538
BACKGROUND: A novel subcutaneous allergen immunotherapy formulation (gpASIT+™) containing Lolium perenne peptides (LPP) and having a short up-dosing phase has been developed to treat grass pollen-induced seasonal allergic rhinoconjunctivitis. We investigated peptide immunotherapy containing the hydrolysate from perennial ryegrass allergens for the optimum dose in terms of clinical efficacy, immunogenicity and safety. METHODS: This prospective, double-blind, placebo-controlled, phase IIb, parallel, four-arm, dose-finding study randomized 198 grass pollen-allergic adults to receive placebo or cumulative doses of 70, 170 or 370 μg LPP. All patients received weekly subcutaneous injections, with the active treatment groups reaching assigned doses within 2, 3 and 4 weeks, respectively. Efficacy was assessed by comparing conjunctival provocation test (CPT) reactions at baseline, after 4 weeks and after completion. Grass pollen-specific immunoglobulins were analysed before and after treatment. RESULTS: Conjunctival provocation test (CPT) response thresholds improved from baseline to V7 by at least one concentration step in 51.2% (170 μg; P = .023), 46.3% (370 μg), and 38.6% (70 μg) of patients receiving LPP vs 25.6% of patients receiving placebo (modified per-protocol set). Also, 39% of patients in the 170-μg group became nonreactive to CPT vs 18% in the placebo group. Facilitated allergen-binding assays revealed a highly significant (P < .001) dose-dependent reduction in IgE allergen binding across all treatment groups (70 μg: 17.1%; 170 μg: 18.8%; 370 μg: 26.4%). Specific IgG4 levels increased to 1.6-fold (70 μg), 3.1-fold (170 μg) and 3.9-fold (370 μg) (mPP). CONCLUSION: Three-week immunotherapy with 170 μg LPP reduced CPT reactivity significantly and increased protective specific antibodies.
Shamji M, Durham SR, 2017, Mechanisms of allergen immunotherapy for inhaled allergens and predictive biomarkers, Journal of Allergy and Clinical Immunology, Vol: 140, Pages: 1485-1498, ISSN: 0091-6749
Allergen immunotherapy is effective in patients with IgEdependentallergic rhinitis and asthma. When immunotherapyis given continuously for 3 years, there is persistent clinicalbenefit for several years after its discontinuation. This diseasemodifyingeffect is both antigen-specific and antigen-driven.Clinical improvement is accompanied by decreases in numbersof effector cells in target organs, including mast cells, basophils,eosinophils, and type 2 innate lymphoid cells. Immunotherapyresults in the production of blocking IgG/IgG4 antibodies thatcan inhibit IgE-dependent activation mediated through bothhigh-affinity IgE receptors (FcεRI) on mast cells and basophilsand low-affinity IgE receptors (FcεRII) on B cells. Suppressionof TH2 immunity can occur as a consequence of either deletionor anergy of antigen-specific T cells; induction of antigenspecificregulatory T cells; or immune deviation in favor of TH1responses. It is not clear whether the altered long-term memoryresides within the T-cell or the B-cell compartment. Recent datahighlight the role of IL-10–producing regulatory B cells and‘‘protective’’ antibodies that likely contribute to long-termtolerance. Understanding mechanisms underlying induction andpersistence of tolerance should identify predictive biomarkers ofclinical response and discover novel and more effectivestrategies for immunotherapy.
This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.