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Intralymphatic immunotherapy with one or two allergens renders similar clinical response in patients with allergic rhinitis due to birch and grass pollen
Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Allergy Center.ORCID iD: 0000-0003-1745-6816
Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
Acad Hlth & Care, Sweden.
Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
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2022 (English)In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 52, no 6, p. 747-759Article in journal (Refereed) Published
Abstract [en]

Introduction

There is a need for a fast, efficient and safe way to induce tolerance in patients with severe allergic rhinitis. Intralymphatic immune therapy has been shown to be effective.

Methods

Patients 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, ALK-Abello), or birch and placebo or 5-grass and placebo by ultrasound-guided injections into inguinal lymph nodes at monthly intervals. Rhinoconjunctivitis total symptom score, medication score and rhinoconjunctivitis quality of life questionnaire were evaluated before treatment and after each birch and grass pollen season during three subsequent years. Circulating proportions of T helper subsets and allergen-induced cytokine and chemokine production were analysed by flow cytometry and Luminex.

Results

The three groups reported fewer symptoms, lower use of medication and improved quality of life during the birch and grass pollen seasons each year after treatment at an almost similar rate independently of treatment with one or two allergens. Mild local pain was the most common adverse event. 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 remained mainly unchanged. Conjunctival challenge tests with timothy extract showed a higher threshold for allergen. In all three groups, regulatory T cell frequencies were increased 3 years after treatment.

Conclusions

Intralymphatic immunotherapy with one or two allergens in patients with grass and birch pollen allergy was safe, effective and may be associated with bystander immune modulatory responses.

Place, publisher, year, edition, pages
Chichester, United Kingdom: Wiley-Blackwell Publishing Inc., 2022. Vol. 52, no 6, p. 747-759
Keywords [en]
allergy; intralymphatic immunotherapy; hypersensitivity; rhinoconjunctivitis immunotherapy; intralymphatic; allergy
National Category
Respiratory Medicine and Allergy
Identifiers
URN: urn:nbn:se:liu:diva-184407DOI: 10.1111/cea.14138ISI: 000776517300001PubMedID: 35332591Scopus ID: 2-s2.0-85127382771OAI: oai:DiVA.org:liu-184407DiVA, id: diva2:1653150
Note

Funding Agencies: Region Östergotland; Medical Research Council of Southeast Sweden (FORSS); Th Bergh Foundation; Asthma and Allergy Association

Available from: 2022-04-21 Created: 2022-04-21 Last updated: 2023-11-27Bibliographically approved
In thesis
1. Intralymphatic Immunotherapy: A Novel Route to Ameliorate Allergic Rhinitis Due to Pollen
Open this publication in new window or tab >>Intralymphatic Immunotherapy: A Novel Route to Ameliorate Allergic Rhinitis Due to Pollen
2024 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Allergy to pollen and animal dander is a major public health problem. Close to 30% of the population have symptoms from the upper and/or lower respiratory tract when they meet fur animals or pollen. Whereas symptom-relieving medications have a good to sufficient effect on about 80% of those affected, a large group of 10–20% have severe symptoms, despite medication, with an impact on well-being and ability to work. In Sweden, the annual cost of allergy was calculated at €1.3 billion in 2014.

Immunotherapy is effective in treating and preventing pollen allergy and allergic asthma, but is expensive, complicated, requiring 40 injections, and takes more than three years to complete if subcutaneous injections are used. Tablets placed under the tongue are another method, with one tablet taken every day for three years. Only 1.5‰ receive such treatment, yet just over 3% would need it.

With intralymphatic immunotherapy, a small dose of allergen is given in a lymph node in the groin on 3 occasions, one month apart. As this method takes only eight weeks, it is a much faster and less costly treatment. However, although several studies have shown that the treatment is safe, its efficacy remains the subject of doubt.

Our pilot study in 2012, with a 3-year follow-up to 2015, showed encouraging results, and was followed by a double-blind randomised study with 72 participants from 2014 to 2018. The research subjects then received treatment with birch and grass pollen extract or one extract and a placebo. Regardless of treatment, symptoms, quality of life and medication consumption improved during the birch and grass pollen seasons in the 3 years after treatment. Increased frequencies of T-regulatory lymphocytes may explain the non-specific effects.

In 2017 to 2018, we conducted a double-blind study with 38 participants, half of whom received placebo and half, active treatment. In this study, we saw no difference between the treatment groups in the first year after treatment. However, after discontinuation and unblinding in 2019, i.e., two years after treatment, the actively treated group improved in terms of symptoms, and quality of life was improved compared with the placebo group despite less need for medication. T-regulatory lymphocytes increased one year after treatment only in the actively treated group.

A long-term follow-up of the research subjects from our two larger studies in 2022, i.e., five to eight years after treatment, showed in the double-blind study without a pure placebo that the scores for symptoms, medication use, and quality of life remained as low as after the first three years. In the placebo-controlled study, a statistically significant improvement in symptoms remained during the grass pollen season. Analysing the two studies together, symptom improvement was significant even during the birch pollen season. Thus, although the effect does not seem to diminish, those who did not receive birch, but only grass, needed to use more medication during the birch pollen season in 2022, seven to eight years after treatment. Moreover, those who did not receive grass but only birch needed more medication during the grass pollen season. This may suggest that the non-specific effect begins to wane after seven to eight years.

Allergy to pollen is a major problem for individuals and society, where symptom-relieving treatment with drugs is not enough for many. They can be helped with immunotherapy, which takes at least three years, is expensive and fraught with side effects. In contrast, intralymphatic immunotherapy involves three injections over eight weeks. Our three studies show that the treatment is safe and indicate that it has a clinical effect up to eight years after treatment. T-regulatory cells appear to be important to the immunological mechanism, leading to tolerance to pollen.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2024. p. 47
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1863
National Category
Respiratory Medicine and Allergy
Identifiers
urn:nbn:se:liu:diva-199359 (URN)10.3384/9789180752527 (DOI)9789180752510 (ISBN)9789180752527 (ISBN)
Public defence
2024-01-19, Belladonna, Building 511, Campus US, Linköping, 09:00
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Supervisors
Note

Funding agencies: Region Östergötland, the Allergy Center in Linköping, the Medical Research Council of Southeast Sweden (FORSS), the Th Bergh Foundation and the Asthma and Allergy Association

Available from: 2023-11-27 Created: 2023-11-27 Last updated: 2023-11-27Bibliographically approved

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