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Allergen Immunotherapy

Intralymphatic immunotherapy with one or two allergens renders similar clinical response in patients with allergic rhinitis due to birch and grass pollen

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Ahlbeck L, Ahlberg E, Björkander J, Aldén C, Papapavlou G, Palmberg L, Nyström U, Retsas P, Nordenfelt P, Togö T, Johansen P, Rolander B, Duchén K, Jenmalm MC

Clin Exp Allergy. 2022 Jun;52(6):747-759. doi: 10.1111/cea.14138. Epub 2022 Apr 1. PMID: 35332591

Nearly 1/3 of the adult population of Sweden report allergic rhinitis. Although the prevalence of allergic sensitization is up to nearly half of the patients, there is a gap for a fast, efficient, and safe way to stimulate tolerance in patients with severe allergic rhinitis.

The aim of this study was to assess the safety and efficacy after intralymphatic immunotherapy with one or two allergens: birch- or grass pollen or both and to determine its immune modulatory effects including changes in spontaneous and allergen-induced cytokine and chemokine production, and proportions of T helper cell subsets in circulation.

People with severe birch and timothy allergy were randomized and received three doses of 0.1 ml of birch and 5-grass allergen extracts (10,000 SQ units/ml), or birch and placebo or 5-grass and placebo by ultrasound-guided injections into inguinal lymph nodes at monthly intervals. Characteristics reported before treatment and after each birch and grass pollen season included: rhinoconjunctivitis total symptom score, medication score and rhinoconjunctivitis quality of life questionnaire and circulating proportions of T helper subsets and allergen-induced cytokine and chemokine production (analysed by flow cytometry and Luminex).

After treatment with one or two allergens, the three groups related less symptoms, littler use of medication and better quality of life during the birch and grass pollen seasons, at an approximate rate. The most common adverse event reported was mild local pain. IgE levels to birch decreased, whereas birch-induced IL-10 secretion increased in all three groups. IgG4 levels to birch and timothy and skin prick test reactivity persisted mainly unaffected. Conjunctival challenge tests with timothy extract indicated a superior threshold for allergen. In all three groups, regulatory T cell frequencies were augmented 3 years after treatment.

In conclusion, intralymphatic immunotherapy with one or two allergens in people with grass and birch pollen allergy was effective and safe and may be associated with other immune modulatory responses.

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Immunological Responses and Biomarkers for Allergen-Specific Immunotherapy Against Inhaled Allergens

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Mohamed H. Shamji, Janice A. Layhadi, Hanisah Sharif, Martin Penagos, Stephen R. Durham

J Allergy Clin Immunol Pract. 2021 Mar 27:S2213-2198(21)00363-9. doi: 10.1016/j.jaip.2021.03.029.

Patients with IgE-mediated rhinoconjunctivitis and/or bronchial asthma who do not respond to symptomatic treatment or have severe side effects are often recommended allergen immunotherapy. Prolonged treatment has shown long-term benefits in patients with moderate to severe allergic rhinitis. The long-term efficacy from allergen immunotherapy represents a decrease in IgE activation of mast cells and tissue eosinophilia, which is accompanied by early induction of regulatory T cells, immune deviation in favor of TH1 responses, and induction of local and systemic IgG and IgA antibodies. These antibodies, whose primary function is to be protective, can prevent the formation of allergen-IgE complex and subsequent activation of the mast cells and TH2 facilitated by IgE.

Some studies demonstrate the importance of innate responses mediated by type 2 dendritic cells and innate lymphoid cells in allergic inflammation. Type 2 dendritic cells and lymphoid cells are regulated by cytokines derived from the respiratory epithelium. New subsets of regulatory cells induced by immunotherapy include:

  • IL-35-producing regulatory T cells,
  • Regulatory B cells,
  • A subset of T follicular regulatory cells, and
  • IL-10-producing group 2 innate lymphoid cells.

These regulatory cells may represent biomarkers that will predict the clinical response to immunotherapy and evaluate the efficacy, safety, and long-term tolerance.

More studies are required to identify candidate biomarkers as a routine immune-monitoring tool for assessing allergen immunotherapy response.

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Alergenos farmacoterapia e inmunologia

Responders and nonresponders to pharmacotherapy and allergen immunotherapy

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Jakalski M, Bozek A, Canonica GW.

A retrospective analysis of 1624 patients with allergic rhinitis who underwent allergen immunotherapy and 1519 matched patients who underwent only symptomatic therapy was performed.

Allergen immunotherapy is a useful treatment for allergic rhinitis; however, some patients do not achieve the expected results and its responsiveness is difficult to assess. The objective of this study was to assess potential reasons for this to happen.

Investigators registered symptoms, medication scores and quality of life related to allergic diseases before and after treatment. A cluster analysis was performed to discover any association between responsiveness to therapy and the parameters registered.

According to the Mailing criteria, which assesses responsiveness to therapy, 77,8% of patients from the allergen immunotherapy group improved 30% or more; and 62,5% of patients met the threshold of 60% or more improvement. Patients with a short history of allergic rhinitis and concomitant allergy to grass pollen or house dust mites were more frequently worse responders to allergen immunotherapy.

In conclusion, the investigators suggest that short term allergic rhinitis and monovalent allergies to grass pollen or mites could correspond to a better response to allergen treatment.

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Rinitis alérgenos y asma en Bélgica

Stepwise approach towards adoption of allergen immunotherapy for allergic rhinitis and asthma patients in daily practice in Belgium: a BelSACI-Abeforcal-EUFOREA statement

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Hellings PW, Pugin B, Mariën G, Bachert C, Breynaert C, et al.

Physicians dealing with Allergic rhinitis (AR) patients should inform patients on tolerance-inducing effects of Allergen immunotherapy (AIT) and are in the need of a harmonized and practical guide that supports them in selecting eligible patients for AIT, in choosing evidence-based AIT products and in following treatment protocols with proven efficacy. Therefore, a stepwise and holistic approach is needed for better adoption of AIT in the real-life setting in Belgium.

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