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- Ahlbeck, Lars, 1964-
(författare)
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Intralymphatic Immunotherapy : A Novel Route to Ameliorate Allergic Rhinitis Due to Pollen
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- 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.
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| 2. |
- Ahlbeck, Lars, 1964-, et al.
(författare)
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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
- 2022
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Ingår i: Clinical and Experimental Allergy. - Chichester, United Kingdom : Wiley-Blackwell Publishing Inc.. - 0954-7894 .- 1365-2222. ; 52:6, s. 747-759
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Tidskriftsartikel (refereegranskat)abstract
- IntroductionThere 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. MethodsPatients 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.
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| 3. |
- Benn, CS, et al.
(författare)
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Mammary epithelial paracellular permeability in atopic and non-atopic mothers versus childhood atopy
- 2004
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Ingår i: Pediatric Allergy and Immunology. - : Wiley. - 0905-6157 .- 1399-3038. ; 15:2, s. 123-126
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Tidskriftsartikel (refereegranskat)abstract
- Sodium/potassium (Na/K) ratios are considered to be a marker of mammary epithelial paracellular permeability. The aim of the present study was to investigate the association between maternal atopy and Na/K ratios in breast milk and the association between Na/K ratios in breast milk and the development of atopy in the offspring. Early and mature milk samples were obtained from 30 atopic and 43 non-atopic women. We found no differences in the Na/K ratios between atopic and non-atopic women. At 18 months of age, 22 (30%) of the children had a positive skin prick test (SPT) and 26 (36%) had symptoms of atopic diseases. Overall, high levels of Na/K compared with low and slightly raised levels of Na/K in the maternal milk tended to be associated with a positive SPT and atopic disease. However, if the mother was atopic, high levels of Na/K in early or mature milk were associated with a significantly increased risk of a positive SPT or atopic disease in the offspring [RR = 4.8 (1.9-12)] whereas no such association was observed in non-atopic mothers [RR = 0.8 (0.4-1.7), p for interaction = 0.001]. Thus, high Na/K levels in the breast milk may be associated with the development of atopy and atopic diseases in the offspring of atopic mothers.
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| 4. |
- Casas, Rosaura, 1954-, et al.
(författare)
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Detection of IgA antibodies to cat, β-lactoglobulin, and ovalbumin allergens in human milk
- 2000
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Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier BV. - 0091-6749 .- 1097-6825. ; 105:6 part 1, s. 1236-1240
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Tidskriftsartikel (refereegranskat)abstract
- Background: The relationship between the development of allergy during infancy and breast-feeding remains controversial. This controversy may be due to individual variations in the composition of human milk. Antibodies to food antigens to which the mother is commonly exposed are present in the milk, but their relationship to allergy is still unknown. IgA antibodies to inhalant allergens have not been previously detected.Objective: Our purpose was to analyze secretory IgA antibody levels to cat, β-lactoglobulin, and ovalbumin allergens in colostrum and mature milk in relation to maternal allergy.Methods: Colostrum and samples of mature milk were obtained after 1 and 3 months of lactation from 53 nursing mothers (17 allergic and 36 nonallergic mothers) and were analyzed for total secretory IgA levels by ELISA and secretory IgA antibodies to cat, β-lactoglobulin, and ovalbumin by an enzyme-amplified ELISA. The specificity of the assays was confirmed by inhibition experiments.Results: Secretory IgA to cat, β-lactoglobulin, and ovalbumin allergens were detected in colostrum as well as mature milk. The levels of secretory IgA to ovalbumin were lower in colostrum from allergic mothers with P = .016, whereas the levels to β-lactoglobulin and cat were similar in the 2 groups. IgA antibodies to ovalbumin were detected in 94% of the colostrum samples from allergic and in all samples from nonallergic mothers, in 82% and 96%, respectively at 1 month, and 53% and 65% at 3 months. Fewer samples had detectable secretory IgA antibodies to β-lactoglobulin than to ovalbumin and cat, and only 33% and 10% of the samples from the allergic and nonallergic mothers, respectively, remained positive at 3 months. All the allergic mothers had detectable IgA to cat in colostrum, whereas 83% and 73% of the samples were positive at 1 and 3 months. The corresponding numbers were 93%, 81%, and 81% in the nonallergic mothers (not significant).Conclusion: Even a low level of exposure of the mucosa (eg, by inhalant allergens) can induce antibody secretion into the milk, both in allergic and nonallergic mothers. (J Allergy Clin Immunol 2000;105:1236-40.)
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| 5. |
- Casas, Rosaura, 1954-, et al.
(författare)
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Downregulation of CXCR6 and CXCR3 in lymphocytes from birch-allergic patients
- 2008
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Ingår i: Scandinavian Journal of Immunology. - : Wiley. - 0300-9475 .- 1365-3083. ; 68:3, s. 351-361
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Tidskriftsartikel (refereegranskat)abstract
- Preferential expression of chemokine receptors on Th1 or Th2 T-helper cells has mostly been studied in cell lines generated in vitro or in animal models, however, results are less well characterized in humans. We determined T-cell responses through chemokine receptor expression on lymphocytes, and cytokine secretion in plasma from birch-allergic and healthy subjects. The expression of CCR2, CCR3, CCR4, CCR5, CCR7, CXCR3, CXCR4, CXCR6, IL-12 and IL-18R receptors was studied on CD4+ and CD8+ cells from birch-allergic (n = 14) and healthy (n = 14) subjects by flow cytometry. The concentration of IL-4, IL-5, IL-10, IL-12, IFN-γ and TNF-α cytokines was measured in plasma from the same individuals using a cytometric bead array human cytokines kit. The similar expression of CCR4 in T cells from atopic and healthy individuals argues against the use of the receptor as an in vivo marker of Th2 immune responses. Reduced percentages of CD4+ cells expressing IL-18R, CXCR6 and CXCR3 were found in the same group of samples. TNF-α, IFN-γ, IL-10, IL-5, IL-4 and IL-12 cytokines were elevated in samples from allergic individuals. Reduced expression of Th1-associated chemokine receptors together with higher levels of Th1, Th2 and anti-inflammatory cytokines in samples from allergic patients indicate that immune responses in peripheral blood in atopic diseases are complex and cannot be simplified to the Th1/Th2 paradigm. Not only the clinical picture of atopic diseases but also the clinical state at different time points of the disease might influence the results of studies including immunological markers associated with Th1- or Th2-type immune responses. © 2008 The Authors.
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| 6. |
- Casas, Rosaura, 1954-, et al.
(författare)
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Impaired maturation of monocyte-derived dendritic cells from birch allergic individuals in association with birch-specific immune responses
- 2007
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Ingår i: Scandinavian Journal of Immunology. - : Wiley. - 0300-9475 .- 1365-3083. ; 66:5, s. 591-598
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Tidskriftsartikel (refereegranskat)abstract
- Optimal activation of T lymphocytes requires a costimulatory signal provided by the interaction of molecules on the surface of T cells with their ligands expressed on dendritic cells (DC). We investigated whether DC differentiated from monocytes from healthy and birch allergic asthmatic individuals and further maturated by stimulation with cat and birch allergens and LPS differ in their phenotypic receptor expression. Similar expression of DC surface markers, including HLA-DR, CD80, CD86, CD83, CD1a and CD11c, was detected in monocyte-derived DC from allergic and healthy individuals. Cells from healthy donors stimulated either antigen showed a similar activation of the CD80 and double CD80/CD86 costimulatory molecules when compared with non-stimulated cells. In the case of cells from allergic individuals, birch allergen was unable to produce the same increased expression of CD80 alone or in combination with CD80/CD86, in comparison with cells stimulated with cat and LPS. Levels of IL-6, IL-8, IL-10, MCP-1/MCAF and MIP-1β were similar in the supernatant of non-stimulated DC from both groups of subjects. By contrast, the spontaneous secretion of IL-12p70 and TNF-α was higher in the supernatant of DC from healthy subjects when compared with that from allergic individuals. Stimulation with birch and LPS resulted in an increased secretion of IL-12p70 in samples from healthy when compared with that in allergic individuals. The results suggest an impaired specific maturation of DC from birch allergic individuals in association with birch-specific immune responses. Lower secretion of IL-12p70 from birch-stimulated DC from allergic individuals suggests that not only maturation, but also the specific Th1 function of these cells seems to be affected in those individuals.
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| 8. |
- Duchén, Karel, 1961-, et al.
(författare)
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Fatty fish intake in mothers during pregnancy and in their children in relation to the development of obesity and overweight in childhood: The prospective ABIS study
- 2020
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Ingår i: Obesity Science and Practice. - : Wiley. - 2055-2238. ; 6:1, s. 57-69
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Tidskriftsartikel (refereegranskat)abstract
- Background: Although controversial, lower maternal intake of n-3 polyunsaturated fatty acid (PUFA) during pregnancy and lower levels of omega-3 PUFA in serum phospholipids during childhood have been related to obesity. The main source of omega-3 PUFA is fatty fish in the diet. Objectives: To assess the relationship between overweight/obesity and the intake of fatty fish in maternal diet during pregnancy and in children up to 8 years of age. Methods: The prospective cohort All Children in South-East Sweden (ABIS) followed babies from birth to 8 years of age. A total of 6749 children at 5 years of age (boys 52.6%) and 3017 children at 8 years (boys 52.3%) participated. A “fatty-fish index” was constructed on the basis of self-reports of nutritional habits. Results: The prevalence of overweight and obesity in children at 5 years were 12.9% and 4.2%, respectively. At 8 years, 12.2% of the children presented overweight and 2.3% obesity. Girls were more affected than boys by overweight/obesity. A higher fish index during pregnancy was not related to overweight/obesity in the children, whereas a higher fish index in the children during the first years of life was related to obesity at 5 and 8 years of age. This relationship disappeared in a multivariable analysis. Maternal body mass index (BMI), maternal education, maternal smoking during pregnancy, birth weight, and physical activity all remained related to overweight/obesity at both 5 and 8 years of age. Conclusion: No relationships were found between a lower intake of fatty fish in the diet, neither in mothers during pregnancy nor in early childhood, and increased risk of overweight/obesity. © 2019 The Authors. Obesity Science & Practice published by World Obesity and The Obesity Society and John Wiley & Sons Ltd
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