Long-term tolerance after allergen immunotherapy is accompanied by selective persistence of blocking antibodies

James, Louisa K.; Shamji, Mohamed H.; Walker, Samantha; Wilson, David E.; Wachholz, Petra A.; Francis, James N.; Jacobson, Mikila R.; Kimber, Ian; Till, Stephen J.; Durham, Stephen R.

doi:10.1016/j.jaci.2010.12.1080

Cited by 300 publications

(259 citation statements)

References 42 publications

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“…SCIT is a conventional treatment, which has more than 100 years of history with proved efficacy (Ring and Gutermuth, 2011). SLIT is a relatively new treatment that started in 1986, however with comparable immunologic mechanisms (Scadding et al, 2010;James et al, 2011). The potential side effects of anaphylaxis in SCIT largely restricted its clinical application, mainly because of the concerns about its safety raised by patients as well as doctors.…”

Section: Discussionmentioning

confidence: 99%

Diagnosis and treatment of allergic diseases in Zhejiang Province: A cross-sectional survey

Wang

Shen

Yang

et al. 2015

J. Zhejiang Univ. Sci. B

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Abstract:Background: The specialty of allergy developed quickly in western countries because of the rapid increase of allergic diseases, whereas it developed relatively slowly in China. The prevalence of allergen sensitization and allergic diseases in Zhejiang Province of China is high and improving the medical services for these diseases is critically needed. Objective: To investigate the working status of the diagnosis and treatment of allergic diseases, including doctor resources, diagnostic methods, and allergen-specific immunotherapy in patients of Zhejiang Province, and to provide instructions for the strategic development of subspecialties of allergic diseases. Methods: First we defined the doctors who treat allergic diseases, and designed a comprehensive questionnaire to collect personal and hospital information for these doctors. The questionnaires were distributed to hospitals with different ranks and from different areas in the province. The general condition of doctor's resources, carryout of diagnostic methods, and allergen-specific immunotherapy were described and variations in the different specialties, hospitals, and areas were further analyzed. Results: Doctors in their thirties with bachelor's degrees were the mainstream for diagnosing and treating allergic diseases. The main specialties of the doctor resources were the specialties of Ear, Nose and Throat (ENT), Respirology, Pediatrics, and Dermatology. The Pediatrics specialty had a more reasonable infrastructure of doctor resources with more young doctors working in this subspecialty. The development of allergy subspecialty varied within hospitals at different levels or from different areas. The carryout of the skin prick test (SPT), serum specific IgE (ssIgE), and subcutaneous immunotherapy (SCIT) was best performed in provincial hospitals, while sublingual immunotherapy (SLIT) was prescribed most commonly in municipal hospitals. The performance of SPT and ssIgE in Hangzhou, Jiaxing, and Wenzhou areas was much better than that in other places. The performance of SCIT and SLIT was best in Wenzhou. Conclusions: Our survey revealed a very initial and unbalanced development for the allergy subspecialty in Zhejiang Province. Doctor resources for allergic diseases were mainly from the specialties of ENT, Respirology, and Pediatrics, and the performance of diagnosis and treatment was mainly focused on provincial and municipal hospitals. Continuous education of allergies could be extended to primary healthcare centers and more efforts should be directed to those areas with poor medical resources.

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Section: Discussionmentioning

confidence: 99%

Diagnosis and treatment of allergic diseases in Zhejiang Province: A cross-sectional survey

Wang

Shen

Yang

et al. 2015

J. Zhejiang Univ. Sci. B

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“…The production of blocking antibodies was assessed using a functional assay 15, 16, 17. Relative allergen‐IgE complex binding to CD23 detected in the presence of patient and indicator serum was expressed as the percentage of binding observed in a reference condition with indicator serum only.…”

Section: Methodsmentioning

confidence: 99%

A randomized, double‐blind, placebo‐controlled, dose‐finding trial with Lolium perenne peptide immunotherapy

Mösges

Kasche

Raskopf

et al. 2017

Allergy

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BackgroundA 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.MethodsThis 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.ResultsConjunctival 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).ConclusionThree‐week immunotherapy with 170 μg LPP reduced CPT reactivity significantly and increased protective specific antibodies.

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“…In general, SIT induces high levels of allergen-specific IgG antibodies, in particular IgG4, which are considered as "blocking" antibodies because they compete with IgE for allergen-binding and thereby impair IgEmediated reactions, e.g. allergen-induced activation of basophils and mast cells or IgEfacilitated allergen uptake and presentation to T cells (James et al, 2011, Nouri-Aria et al, 2004, van Neerven et al, 1999, Wachholz et al, 2003. At the T cell level it has been demonstrated that SIT induces a shift from the disease-eliciting T helper (Th) 2-towards a Th1-like response and regulatory CD4 + T (Treg) cells that actively suppress proliferation and cytokine production of allergen-specific effector T cells (Akdis et al, 1998, Bellinghausen et al, 1997, Ebner et al, 1997, Jutel et al, 2003.…”

Section: Specific Immunotherapy With Birch Pollenmentioning

confidence: 99%

Birch Pollen-Related Food Allergy: An Excellent Disease Model to Understand the Relevance of Immunological Cross-Reactivity for Allergy

Subbarayal¹,

Geroldinger‐Simic²,

Bohle³

2012

Allergic Diseases - Highlights in the Clinic, Mechanisms and Treatment

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Long-term tolerance after allergen immunotherapy is accompanied by selective persistence of blocking antibodies

Cited by 300 publications

References 42 publications

Diagnosis and treatment of allergic diseases in Zhejiang Province: A cross-sectional survey

Diagnosis and treatment of allergic diseases in Zhejiang Province: A cross-sectional survey

A randomized, double‐blind, placebo‐controlled, dose‐finding trial with Lolium perenne peptide immunotherapy

Birch Pollen-Related Food Allergy: An Excellent Disease Model to Understand the Relevance of Immunological Cross-Reactivity for Allergy

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