| 1. |
- Ameur, Adam, et al.
(författare)
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SweGen : a whole-genome data resource of genetic variability in a cross-section of the Swedish population
- 2017
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Ingår i: European Journal of Human Genetics. - : NATURE PUBLISHING GROUP. - 1018-4813 .- 1476-5438. ; 25:11, s. 1253-1260
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Tidskriftsartikel (refereegranskat)abstract
- Here we describe the SweGen data set, a comprehensive map of genetic variation in the Swedish population. These data represent a basic resource for clinical genetics laboratories as well as for sequencing-based association studies by providing information on genetic variant frequencies in a cohort that is well matched to national patient cohorts. To select samples for this study, we first examined the genetic structure of the Swedish population using high-density SNP-array data from a nation-wide cohort of over 10 000 Swedish-born individuals included in the Swedish Twin Registry. A total of 1000 individuals, reflecting a cross-section of the population and capturing the main genetic structure, were selected for whole-genome sequencing. Analysis pipelines were developed for automated alignment, variant calling and quality control of the sequencing data. This resulted in a genome-wide collection of aggregated variant frequencies in the Swedish population that we have made available to the scientific community through the website https://swefreq.nbis.se. A total of 29.2 million single-nucleotide variants and 3.8 million indels were detected in the 1000 samples, with 9.9 million of these variants not present in current databases. Each sample contributed with an average of 7199 individual-specific variants. In addition, an average of 8645 larger structural variants (SVs) were detected per individual, and we demonstrate that the population frequencies of these SVs can be used for efficient filtering analyses. Finally, our results show that the genetic diversity within Sweden is substantial compared with the diversity among continental European populations, underscoring the relevance of establishing a local reference data set.
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| 2. |
- Lundin, Johan, et al.
(författare)
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Diagnosis of soil-transmitted helminth infections with digital mobile microscopy and artificial intelligence in a resource-limited setting
- 2024
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Ingår i: PLoS Neglected Tropical Diseases. - : Public Library of Science (PLoS). - 1935-2727 .- 1935-2735. ; 18:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Infections caused by soil-transmitted helminths (STHs) are the most prevalent neglected tropical diseases and result in a major disease burden in low- and middle-income countries, especially in school-aged children. Improved diagnostic methods, especially for light intensity infections, are needed for efficient, control and elimination of STHs as a public health problem, as well as STH management. Image-based artificial intelligence (AI) has shown promise for STH detection in digitized stool samples. However, the diagnostic accuracy of AI-based analysis of entire microscope slides, so called whole-slide images (WSI), has previously not been evaluated on a sample-level in primary healthcare settings in STH endemic countries.Methodology/Principal findings: Stool samples (n = 1,335) were collected during 2020 from children attending primary schools in Kwale County, Kenya, prepared according to the Kato-Katz method at a local primary healthcare laboratory and digitized with a portable whole-slide microscopy scanner and uploaded via mobile networks to a cloud environment. The digital samples of adequate quality (n = 1,180) were split into a training (n = 388) and test set (n = 792) and a deep-learning system (DLS) developed for detection of STHs. The DLS findings were compared with expert manual microscopy and additional visual assessment of the digital samples in slides with discordant results between the methods. Manual microscopy detected 15 (1.9%) Ascaris lumbricoides, 172 (21.7%) Tricuris trichiura and 140 (17.7%) hookworm (Ancylostoma duodenale or Necator americanus) infections in the test set. Importantly, more than 90% of all STH positive cases represented light intensity infections. With manual microscopy as the reference standard, the sensitivity of the DLS as the index test for detection of A. lumbricoides, T. trichiura and hookworm was 80%, 92% and 76%, respectively. The corresponding specificity was 98%, 90% and 95%. Notably, in 79 samples (10%) classified as negative by manual microscopy for a specific species, STH eggs were detected by the DLS and confirmed correct by visual inspection of the digital samples.Conclusions/Significance: Analysis of digitally scanned stool samples with the DLS provided high diagnostic accuracy for detection of STHs. Importantly, a substantial number of light intensity infections were missed by manual microscopy but detected by the DLS. Thus, analysis of WSIs with image-based AI may provide a future tool for improved detection of STHs in a primary healthcare setting, which in turn could facilitate monitoring and evaluation of control programs.
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| 3. |
- Adamsson, Jenni, 1977, et al.
(författare)
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Gastric expression of IL-17A and IFNγ in Helicobacter pylori infected individuals is related to symptoms
- 2017
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Ingår i: Cytokine. - : Elsevier BV. - 1043-4666. ; 99, s. 30-34
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Tidskriftsartikel (refereegranskat)abstract
- Background: Chronic infection with Helicobacter pylori leads to gastritis and in a subpopulation of infected individuals to ulcers and cancer. Bacterial virulence factors and host immune inflammatory responses are risk factors related to disease. CD4+ T cells secrete cytokines that promote inflammation and an anti-bacterial response in the gastric mucosa during infection. The aim of the study was to investigate the pattern of expression of CD4+ T cell derived cytokines, IL-17A and IFNγ in paired antrum and corpus biopsies and correlate it to H. pylori infection outcome. Methods: Gene and protein expression of IL-17A and IFNγ was analyzed in gastric biopsies from H. pylori infected subjects with non-ulcer dyspepsia (NUD) or gastric ulcer; and for comparison uninfected individuals. Results: Upregulation of IL-17A and IFNγ gene expression was seen in corpus and antrum biopsies of H. pylori infected individuals with NUD compared to in uninfected controls. The expression of these cytokines correlated significantly with each other. Immunofluorescence staining revealed increased frequencies of IL-17A+ and IFNγ+ cells in antrum biopsies of gastric ulcer patients compared to of H. pylori infected NUD individuals; positive cells were not detected in any of the biopsies of uninfected controls. The frequencies of IFNγ and IL-17A+ cells correlated positively with inflammation in the antrum, but not the corpus, of H. pylori infected individuals. In the antrum, while there was no significant evidence of correlation between IFNγ and bacterial score, a positive correlation between bacterial score and IL-17A+ cells was seen. Conclusions: In H. pylori infected individuals, the frequencies of IFNγ and IL-17A+ cells were increased in the antrum, particularly in patients with H. pylori induced gastric ulcers. Even though H. pylori colonized both the corpus and antrum regions of the stomach, the cytokine responses and subsequent pathology were mainly detected in the antrum. © 2017 Elsevier Ltd
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| 4. |
- Adamsson, Jenni, 1977, et al.
(författare)
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Immune Responses Against Helicobacter pylori in Gastric Cancer Patients and in Risk Groups for Gastric Cancer.
- 2013
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Ingår i: Helicobacter. - : Wiley. - 1523-5378 .- 1083-4389. ; 18:1, s. 73-82
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: It has previously been reported that weak serum IgG but elevated IgA antibody responses against H.pylori may be associated with risk of gastric cancer (GC) development. To search for potential immunologic markers for GC, we analyzed antibody responses against H.pylori in risk groups of cancer development. MATERIAL AND METHODS: Sera and stomach biopsies collected from H.pylori-infected GC patients as well as from patients with gastric ulcer (GU), atrophic gastritis, intestinal metaplasia (IM) and duodenal ulcer and from H.pylori-infected control subjects without atrophy or IM, and in addition from H.pylori-negative subjects were analyzed for IgG and IgA antibodies against three different H.pylori antigen preparations, that is, membrane protein (MP), urease, and CagA. RESULTS: We observed an increased serum IgA/IgG titer ratio against H.pylori anti-MP in GC and GU patients, and against CagA in Hp-infected GC patients and risk groups. Female patients with GC had a higher serum anti-MP IgA/IgG titer ratio and a higher proportion of poorly differentiated cancer compared with male patients. As earlier observed, the non-tumorous mucosa of H.pylori-infected GC patients contained considerably lower levels of total IgA and H.pylori-specific IgA compared with H.pylori-infected controls. Similarly, we observed decreased specific mucosal anti-MP IgA response in patients with IM. CONCLUSION: We observed several differences in local and systemic immunologic responses against H.pylori in H.pylori-infected GC patients and putative GC risk group patients compared with H.pylori-infected controls. These findings may be of importance in efforts to identify risk groups of GC or early stages of GC.
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| 5. |
- Azem, Josef, 1961, et al.
(författare)
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B cells pulsed with Helicobacter pylori antigen efficiently activate memory CD8+ T cells from H. pylori-infected individuals
- 2005
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Ingår i: Clin Immunol. - : Elsevier BV. ; 118:2-3, s. 284-91
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Tidskriftsartikel (refereegranskat)abstract
- Helicobacter pylori infection causes chronic gastritis that may progress to peptic ulcers or gastric adenocarcinoma and thereby cause major world-wide health problems. Previous studies have shown that CD4+ T cells are important in the immune response to H. pylori in humans, but the role of CD8+ T cells is less clear. In order to study the CD8+ T cell response to H. pylori in greater detail, we have evaluated efficient conditions for activation of CD8+ T cells in vitro. We show that H. pylori-reactive CD8+ T cells can be activated most efficiently by B cells or dendritic cells pulsed with H. pylori antigens. We further show that the majority of CD8+ T cells in H. pylori-infected gastric mucosa are memory cells, and that memory CD8+ T cells sorted from peripheral blood of H. pylori-infected individuals respond 15-fold more to H. pylori urease compared to memory cells from uninfected subjects. We conclude that CD8+ T cells do participate in the immune response to H. pylori, and this may have implications for the development of more severe disease outcomes in H. pylori-infected subjects.
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| 6. |
- Bhuiyan, Taufiqur Rahman, 1974, et al.
(författare)
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Cholera caused by Vibrio cholerae O1 induces T-cell responses in the circulation.
- 2009
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Ingår i: Infection and immunity. - 1098-5522. ; 77:5, s. 1888-93
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Tidskriftsartikel (refereegranskat)abstract
- Considerable effort is being made to understand the acute and memory antibody responses in natural cholera infection, while rather less is known about the roles of cellular immune responses involving T and B lymphocytes. We studied responses in adult patients hospitalized with cholera caused by Vibrio cholerae O1. Peripheral blood mononuclear cells from patients (n = 15) were analyzed by flow cytometry after stimulation with V. cholerae O1 membrane protein (MP) or toxin-coregulated pilus antigen (TcpA). The gamma interferon (IFN-gamma) and interleukin-13 (IL-13) responses in stimulated-lymphocyte supernatants were studied. The responses were compared with those of healthy controls (n = 10). Patients responded with increased frequencies of gut-homing CD4(+) T cells (CD4(+) beta7(+)), gut-homing CD8(+) T cells (CD8(+) beta7(+)), and gut-homing B cells (CD19(+) beta7(+)) at the early and/or late convalescent stages compared to the acute stage. After stimulation with MP or TcpA, proliferation of CD4(+) and CD8(+) T cells was increased at the acute stage and/or early convalescent stage compared to healthy controls. Increased IL-13 and IFN-gamma responses were observed after antigenic stimulation at the acute and convalescent stages compared to healthy controls. Thus, increases in the levels of gut-homing T and B cells, as well as involvement of CD8 and CD4 Th1-mediated (IFN-gamma) and CD4 Th2-mediated (IL-13) cytokine responses, take place in acute dehydrating disease caused by V. cholerae O1. Further studies are needed to determine if such responses are also stimulated after immunization with oral cholera vaccines and if these responses play a role in protection following exposure to cholera.
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| 7. |
- Bhuiyan, Taufiqur Rahman, 1974, et al.
(författare)
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Th1 and Th17 responses to Helicobacter pylori in Bangladeshi infants, children and adults
- 2014
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:4
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Tidskriftsartikel (refereegranskat)abstract
- Both Th1 and Th17 cells are important components of the immune response to Helicobacter pylori (Hp) in adults, but less is known about T cell responses to Hp during early childhood, when the infection is often acquired. We investigated Th1 and Th17 type responses to Hp in adults, children and infants in Bangladesh, where Hp is highly endemic. IL-17 and IFN-γ mRNA levels in gastric biopsies from Hp-infected Bangladeshi adults were analyzed and compared to levels in infected and uninfected Swedish controls. Since biopsies could not be collected from infants and children, cytokine responses in Bangladeshi infants (6-12 months), children (3-5 years) and adults (>19 years) were instead compared by stimulating peripheral blood mononuclear cells (PBMCs) with a Hp membrane preparation (MP) and analyzing culture supernatants by ELISA and cytometric bead array. We found significantly higher expression of IL-17 and IFN-γ mRNA in gastric mucosa of Hpinfected Bangladeshi and Swedish adults compared to uninfected Swedish controls. PBMCs from all age groups produced IL-17 and IFN-γ after MP stimulation, but little Th2 cytokines. IL-17 and IFN-γ were primarily produced by CD4+ T cells, since CD4 + T cell depleted PBMCs produced reduced amounts of these cytokines. Infant cells produced significantly more IL-17, but similar levels of IFN-γ, compared to adult cells after MP stimulation. In contrast, polyclonal stimulation induced lower levels IL-17 and IFN-γ in infant compared to adult PBMCs and CD4+ T cells. The strong IL-17 production in infants after MP stimulation was paralleled by significantly higher production of the IL-17 promoting cytokine IL-1β from infant compared to adult PBMCs and monocytes. In conclusion, these results show that T cells can produce high levels of IL-17 and IFN-β in response to Hp from an early age and indicate a potential role for IL-1β in promoting Th17 responses to Hp during infancy. © 2014 Bhuiyan et al.
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| 8. |
- Bjersing, Jan, 1966, et al.
(författare)
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Synergistic action of immunostimulatory DNA and fcgamma receptor IIB-crosslinking on B-cell phenotype and function
- 2005
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Ingår i: Immunobiology. - : Elsevier BV. - 0171-2985. ; 210:1, s. 23-32
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Tidskriftsartikel (refereegranskat)abstract
- CpG DNA functions via the toll-like receptor-9 (TLR-9) receptor, inducing B cell proliferation and promoting immunoglobulin production. B cell responses to CpG DNA-containing immune complexes could be important in chronic autoimmunity and immune responses to bacterial components. Therefore, we investigated the potential synergy of CpG DNA-stimulation with FcgammaR clustering (CFR) on splenic B cell activity. CFR-induced splenocyte proliferation was significantly increased compared to treatment with CpG DNA alone. While the levels of interleukin-10 (IL-10) were increased in CpG DNA-treated splenocyte cultures, particularly following FcgammaRII/III-clustering, CFR treatment reduced IL-6 levels. B-cell maturation in culture was enhanced by CFR. Indeed, the frequency of IgG expressing cells after stimulation with CpG DNA was increased and was even higher after CFR stimulation. Furthermore, the frequency of plasma cell precursors was markedly increased by stimulation with CFR. Late splenic B cell subsets, transitional type 2 (T2) and mature (M) B cells, responded strongly to CpG DNA with proliferation and the response was enhanced by FcgammaR-clustering. Immature transitional type 1 (T1) B cells showed distinctly lower proliferative response to CpG DNA and very small effects of FcgammaR-clustering, despite similar expression of Fcgamma-receptors by all B cell subsets. In conclusion, these data show synergistic impact of CpG DNA and simultaneous FcgammaR-clustering on B cell proliferation and differentiation.
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| 9. |
- Brisslert, Mikael, 1974, et al.
(författare)
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Helicobacter pylori induce neutrophil transendothelial migration: role of the bacterial HP-NAP
- 2005
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Ingår i: FEMS Microbiol Lett. ; 249:1, s. 95-103
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Tidskriftsartikel (refereegranskat)abstract
- Continuous recruitment of neutrophils into the inflamed gastric mucosal tissue is a hallmark of Helicobacter pylori infection in humans. In this study, we examined the ability of H. pylori to induce transendothelial migration of neutrophils using a transwell system consisting of a cultured monolayer of human endothelial cells as barrier between two chambers. We showed for the first time that live H. pylori, but not formalin-killed bacteria, induced a significantly increased transendothelial migration of neutrophils. H. pylori conditioned culture medium also induced significantly increased transendothelial migration, whereas heat-inactivated culture filtrates had no effect, suggesting that the chemotactic factor was proteinaceous. Depletion of H. pylori-neutrophil activating protein (HP-NAP) from the culture filtrates resulted in significant reduction of the transmigration. Culture filtrates from isogenic HP-NAP deficient mutant bacteria also induced significantly less neutrophil migration than culture filtrates obtained from wild-type bacteria. HP-NAP did not induce endothelial cell activation, suggesting that HP-NAP acts directly on the neutrophils. In conclusion, our results demonstrate that secreted HP-NAP is one of the factors resulting in H. pylori induced neutrophil transendothelial migration. We propose that HP-NAP contributes to the continuous recruitment of neutrophils to the gastric mucosa of H. pylori infected individuals.
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| 10. |
- Dahlman-Höglund, Anna, 1964, et al.
(författare)
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Antibodies given orally in the neonatal period can affect the immune response for two generations: evidence for active maternal influence on the newborn's immune system.
- 1999
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Ingår i: Scandinavian journal of immunology. - 0300-9475. ; 50:6, s. 651-6
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Tidskriftsartikel (refereegranskat)abstract
- Two day old Wistar rats were tube fed with 1 or 10 micrograms of a mouse IgG1 monoclonal anti-idiotypic (a-Id) antibody that was directed against an anti-Escherichia coli-K13 capsular polysaccharide antibody. A control group was given 10 micrograms of an unrelated control antibody. Six weeks after the administration of antibodies, the rats were intestinally colonised with an ovalbumin (OVA)-producing E. coli O6K13 strain. At 8 weeks of age, the male rats (first generation) and the offsprings of the female rats (second generation), were parenterally immunised with OVA and dead wild type E. coli O6K13, and the immune response was followed. In the rats of the first generation, there were no major differences between the groups in the immune response to the bacterium. However, the offspring of the neonatally a-Id administered rats had a profoundly affected immune response to the idiotypically connected antigen K13, but also to other antigens on the bacteria. Thus, a-Id treatment in the first generation gave, in the second generation, a greatly enhanced serum antibody response to the spatially related antigens OVA and O6 LPS, as well as to the idiotypically connected antigen K13. Concurrently, the in vitro spleen cell proliferative response to both OVA and the wild type bacterium was lowered. Overall, greater effects were seen with the higher dose of a-Id. In conclusion, our results demonstrate that by giving monoclonal antibodies idiotypically connected to a single bacterial component to neonatal rats, one profoundly influence the immune response also to other-spatially related-bacterial antigens in their offsprings.
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