| 1. |
- Ahlbeck, Lars, 1964-, et al.
(author)
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Intralymphatic allergen immunotherapy against pollen allergy. A 3-year open follow-up study of 10 patients
- 2018
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In: Annals of Allergy, Asthma & Immunology. - : Elsevier. - 1081-1206 .- 1534-4436. ; 121:5, s. 626-627
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Journal article (peer-reviewed)abstract
- To date, allergen immunotherapy (AIT) is the only treatment that affects the long-term development of allergic rhinoconjunctivitis and induces clinical tolerance primarily by stimulating regulatory T (Treg) cells, attenuating T helper 2 (Th2) responses and synthesis of blocking antibodies1. Conventional AIT with subcutaneous injections, sublingual tablets or drops is effective, but consumes time and resources 2.
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| 2. |
- Ahlbeck, Lars, et al.
(author)
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Intralymphatic immunotherapy with birch and grass pollen extracts. A randomized double-blind placebo-controlled clinical trial
- 2023
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In: Clinical and Experimental Allergy. - : WILEY. - 0954-7894 .- 1365-2222. ; 53:8, s. 809-820
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Journal article (peer-reviewed)abstract
- IntroductionThere is a need to evaluate the safety and efficacy of intralymphatic immunotherapy (ILIT) for inducing tolerance in patients with allergic rhinitis. MethodsThirty-seven patients with seasonal allergic symptoms to birch and grass pollen and skin prick test >3 mm and/or IgE to birch and timothy >0.35 kU/L were randomized to either ILIT, with three doses of 0.1 mL of birch pollen and 5-grass pollen allergen extracts on aluminium hydroxide (10,000 SQ-U/ml; ALK-Abello) or placebo using ultrasound-guided intralymphatic injections at monthly intervals. Daily combined symptom medical score and rhinoconjunctivitis total symptom score were recorded during the peak pollen seasons the year before and after treatment. Rhinoconjunctivitis total symptom score, medication score and rhinoconjunctivitis quality of life questionnaire were recorded annually starting 2 years after treatment. Circulating proportions of T helper cell subsets and allergen-induced cytokine and chemokine production were analysed using flow cytometry and ELISA. ResultsThere were no differences between the groups related to daily combined symptom medical score the year before and after treatment. Two years after ILIT (after unblinding), the actively treated group reported significantly fewer symptoms, lower medication use and improved quality of life than did the placebo group. After the pollen seasons the year after ILIT, T regulatory cell frequencies and grass-induced IFN-gamma levels increased only in the actively treated group. ConclusionIn this randomized controlled trial, ILIT with birch and grass pollen extract was safe and accompanied by immunological changes. Further studies are required to confirm or refute the efficacy of the treatment.
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| 3. |
- Ahlbeck, Lars, 1964-, et al.
(author)
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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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In: Clinical and Experimental Allergy. - Chichester, United Kingdom : Wiley-Blackwell Publishing Inc.. - 0954-7894 .- 1365-2222. ; 52:6, s. 747-759
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Journal article (peer-reviewed)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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| 4. |
- Ahlberg, Emelie, et al.
(author)
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Breast milk microRNAs : Potential players in oral tolerance development
- 2023
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In: Frontiers in Immunology. - : Frontiers Media S.A.. - 1664-3224. ; 14
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Research review (peer-reviewed)abstract
- Breast milk is an essential source of nutrition and hydration for the infant. In addition, this highly complex biological fluid contains numerous immunologically active factors such as microorganisms, immunoglobulins, cytokines and microRNAs (miRNAs). Here, we set out to predict the function of the top 10 expressed miRNAs in human breast milk, focusing on their relevance in oral tolerance development and allergy prevention in the infant. The top expressed miRNAs in human breast milk were identified on basis of previous peer-reviewed studies gathered from a recent systematic review and an updated literature search. The miRNAs with the highest expression levels in each study were used to identify the 10 most common miRNAs or miRNA families across studies and these were selected for subsequent target prediction. The predictions were performed using TargetScan in combination with the Database for Annotation, Visualization and Integrated Discovery. The ten top expressed miRNAs were: let-7-5p family, miR-148a-3p, miR-30-5p family, miR-200a-3p + miR-141-3p, miR-22-3p, miR-181-5p family, miR-146b-5p, miR-378a-3p, miR-29-3p family, miR-200b/c-3p and miR-429-3p. The target prediction identified 3,588 potential target genes and 127 Kyoto Encyclopedia of Genes and Genomes pathways; several connected to the immune system, including TGF-b and T cell receptor signaling and T-helper cell differentiation. This review highlights the role of breast milk miRNAs and their potential contribution to infant immune maturation. Indeed, breast milk miRNAs seem to be involved in several pathways that influence oral tolerance development.
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| 5. |
- Ahlberg, Emelie, et al.
(author)
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Evaluation of five column-based isolation kits and their ability to extract miRNA from human milk
- 2021
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In: Journal of Cellular and Molecular Medicine (Print). - : Wiley-Blackwell Publishing Inc.. - 1582-1838 .- 1582-4934. ; 25:16, s. 7973-7979
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Journal article (peer-reviewed)abstract
- MicroRNA can be found in various body fluids, including breast milk. MicroRNA may be transferred from mother to infant via breast milk and potentially regulate the development of the infant's immune system on a post-transcriptional level. This study aimed to determine the microRNA extraction efficiency of five RNA extraction kits from human skim milk samples. Their efficiency was determined by comparing microRNA concentrations, total RNA yield and purity. Furthermore, hsa-miR-148a-3p expression and the recovery of an exogenous control, cel-miR-39-3p, were quantified using qPCR. Each kit extracted different amounts of microRNA and total RNA, with one kit tending to isolate the highest amount of both RNA species. Based on these results, the extraction kit ReliaPrep™ miRNA Cell and Tissue Miniprep System from Promega was found to be the most appropriate kit for microRNA extraction from human skim milk. Moreover, further research is needed to establish a standardized protocol for microRNA extraction from breast milk.
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| 6. |
- Ahlberg, Emelie, et al.
(author)
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Immune-related microRNAs in breast milk and their relation to regulatory T cells in breastfed children
- 2023
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In: Pediatric Allergy and Immunology. - : Munksgaard Forlag. - 0905-6157 .- 1399-3038. ; 34:4
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Journal article (peer-reviewed)abstract
- BACKGROUND: The immunomodulatory capacity of breast milk may partially be mediated by microRNAs (miRNA), small RNA molecules that regulate gene expression on a post-transcriptional level and are hypothesized to be involved in modulation of immunological pathways. Here, we evaluate the expression of immune-related miRNAs in breast milk after pre- and postnatal supplementation with Limosilactobacillus reuteri and omega-3 (ω-3) polyunsaturated fatty acids (PUFAs), and the association to infant regulatory T cell (Treg) frequencies.METHODS: One-hundred and twenty women included in a double-blind, randomized, placebo-controlled allergy intervention trial received L. reuteri and/or ω-3 PUFAs daily from gestational week 20. Using Taqman qPCR, 24 miRNAs were analyzed from breast milk obtained at birth (colostrum) and after 3 months (mature milk) of lactation. The proportion of activated and resting Treg cells were analyzed in infant blood using flow cytometry at 6, 12, and 24 months.RESULTS: Relative expression changed significantly over the lactation period for most of the miRNAs; however, the expression was not significantly influenced by any of the supplements. Colostrum miR-181a-3p correlated with resting Treg cell frequencies at 6 months. Colostrum miR-148a-3p and let-7d-3p correlated with the frequencies of activated Treg cells at 24 months, as did mature milk miR-181a-3p and miR-181c-3p.CONCLUSION: Maternal supplementation with L. reuteri and ω-3 PUFAs did not significantly affect the relative miRNA expression in breast milk. Interestingly, some of the miRNAs correlate with Treg subpopulations in the breastfed children, supporting the hypothesis that breast milk miRNAs could be important in infant immune regulation. TRIAL REGISTRATION: ClinicalTrials.gov-ID: NCT01542970.
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| 7. |
- Looft, Emelie, et al.
(author)
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Duration of second stage of labour at term and pushing time : risk factors for postpartum haemorrhage
- 2017
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In: Paediatric and Perinatal Epidemiology. - Stockholm : Karolinska Institutet, Dept of Medicine, Solna. - 0269-5022 .- 1365-3016.
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Journal article (peer-reviewed)abstract
- BACKGROUND: Prolonged labour is associated with increased risk of postpartum haemorrhage (PPH), but the role of active pushing time and the relation with management during labour remains poorly understood. METHODS: A population-based cohort study from electronic medical record data in the Stockholm-Gotland Region, Sweden. We included 57 267 primiparous women with singleton, term gestation, livebirths delivered vaginally in cephalic presentation in 2008-14. We performed multivariable Poisson regression to estimate the association between length of second stage, pushing time, and PPH (estimated blood loss >500 mL during delivery), adjusting for maternal, delivery, and fetal characteristics as potential confounders. RESULTS: The incidence of PPH was 28.9%. The risk of PPH increased with each passing hour of second stage: compared with a second stage <1 h, the adjusted relative risk (RR) for PPH were for 1 to <2 h 1.10 (95% confidence interval (CI) 1.07, 1.14); for 2 to <3 h 1.15 (95% CI 1.10, 1.20); for 3 to <4 h 1.28 (95% CI 1.22, 1.33); and for ≥4 h 1.40 (95% CI 1.33, 1.46). PPH also increased with pushing time exceeding 30 min. Compared to pushing time between 15 and 29 min, the RR for PPH were for <15 min 0.98 (95% CI 0.94, 1.03); for 30-44 min 1.08 (95% CI 1.04, 1.12); for 45-59 min 1.11 (95% CI 1.06, 1.16); and for ≥60 min 1.20 (95% CI 1.15, 1.25). CONCLUSIONS: Increased length of second stage and pushing time during labour are both associated with increased risk of PPH.
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| 8. |
- Lundqvist, Adam, et al.
(author)
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Socioeconomic inequalities in breast cancer incidence and mortality in Europe - A systematic review and meta-analysis
- 2016
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In: European Journal of Public Health. - : Oxford University Press (OUP). - 1101-1262 .- 1464-360X. ; 26:5, s. 804-813
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Journal article (peer-reviewed)abstract
- Background: Breast cancer is the leading cause of female cancer in Europe and is estimated to affect more than one in 10 women. Higher socioeconomic status has been linked to higher incidence but lower case fatality, while the impact on mortality is ambiguous. Methods: We performed a systematic literature review and meta-analysis on studies on association between socioeconomic status and breast cancer outcomes in Europe, with a focus on effects of confounding factors. Summary relative risks (SRRs) were calculated. Results: The systematic review included 25 articles of which 8 studied incidence, 10 case fatality and 8 mortality. The meta-analysis showed a significantly increased incidence (SRR 1.25, 1.17-1.32), a significantly decreased case fatality (SRR 0.72, 0.63-0.81) and a significantly increased mortality (SRR 1.16, 1.10-1.23) for women with higher socioeconomic status. The association for incidence became insignificant when reproductive factors were included. Case fatality remained significant after controlling for tumour characteristics, treatment factors, comorbidity and lifestyle factors. Mortality remained significant after controlling for reproductive factors. Conclusion: Women with higher socioeconomic status show significantly higher breast cancer incidence, which may be explained by reproductive factors, mammography screening, hormone replacement therapy and lifestyle factors. Lower case fatality for women with higher socioeconomic status may be partly explained by differences in tumour characteristics, treatment factors, comorbidity and lifestyle factors. Several factors linked to breast cancer risk and outcome, such as lower screening attendance for women with lower socioeconomic status, are suitable targets for policy intervention aimed at reducing socioeconomic-related inequalities in health outcomes.
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| 9. |
- Tingö, Lina, 1984-, et al.
(author)
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Non-Coding RNAs in Human Breast Milk : A Systematic Review
- 2021
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In: Frontiers in Immunology. - : Frontiers Media S.A.. - 1664-3224. ; 12
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Research review (peer-reviewed)abstract
- Breast milk is the primary source of nutrition and hydration for the newborn infant but also plays an important role in the child's first immune defense. Additionally, several breast milk factors have been implicated in immune-related health outcomes later in life, including immunoglobulins, cytokines, chemokines, growth factors and, more recently, non-coding RNA (ncRNA) species. In this systematic review, we provide a comprehensive summary of the current literature on endogenous ncRNAs found in human breast milk. Thirty (30) relevant studies were identified and, whilst the majority studies focused on microRNAs (miRNAs), there is evidence that breast milk contains high quantities of RNA which also include long-coding RNAs, circular RNAs, as well as other short RNAs and fragmented tRNA and rRNAs. Among studies investigating miRNAs, miR-148a-3p, miR-30a/d-5p, miR-22-3p, miR-146b-5p, miR-200a/c-3p, and the 5p end of the let-7 miRNAs were commonly reported among the top 10 miRNAs in the cell, lipid, and skim milk fractions of breast milk. Methodological difference and small sample sizes limit the possibility of conclusively identifying which maternal and infant characteristics affect the miRNA profile. The highly expressed miRNAs were generally reported to be similar across lactational stage, milk fraction, maternal and infant characteristics, or infant growth and health. All the same, individual studies identify potential differences in miRNA expression levels which should be confirmed by future studies. Stability, uptake, and physiological functions of miRNAs were also considered in several studies. Breast milk miRNAs are relatively resistant to a range of harsh conditions and uptake experiments suggest that extracellular vesicles containing miRNAs and circular RNAs can be taken up by intestinal epithelial cells. Although the evidence regarding the functional effect of breast milk miRNAs is limited, the predicted functions range from metabolic and biosynthetic processes to signaling pathways, cellular adhesion, communication, growth, and differentiation. Finally, this systematic review highlights some of the methodological challenges and knowledge gaps which can help direct future research in this field. In particular, it is important to further investigate the bioavailability of miRNAs in different milk fractions, and to characterize other ncRNAs which are largely unstudied.Systematic Review Registration: PROSPERO https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=138989, identifier CRD42020138989.
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