Publications by authors named "Kerstin Andersson"

42 Publications

Adipocytokines in Untreated Newly Diagnosed Rheumatoid Arthritis: Association with Circulating Chemokines and Markers of Inflammation.

Biomolecules 2021 Feb 21;11(2). Epub 2021 Feb 21.

Department of Rheumatology and Inflammation Research, Institute of Medicine, The Sahlgrenska Academy at University of Gothenburg, 413 46 Gothenburg, Sweden.

Adiponectin, leptin, and resistin are adipocytokines whose levels are elevated in blood and synovial fluid from patients with rheumatoid arthritis (RA). However, their role in RA pathogenesis is unclear. Here, we examined whether adipocytokines are associated with circulating chemokines, markers of inflammation and RA disease activity in patients with untreated newly diagnosed RA. Plasma levels of 15 chemokines, adiponectin, leptin, and resistin were measured using flow cytometry bead-based immunoassay or enzyme-linked immunosorbent assay (ELISA) in a cohort of 70 patients with untreated newly diagnosed RA. Markers of inflammation and disease activity were also assessed in all patients. Positive association was found between total adiponectin and CXCL10 (β = 0.344, = 0.021), CCL2 (β = 0.342, = 0.012), and CXCL9 (β = 0.308, = 0.044), whereas high-molecular weight (HMW) adiponectin associated only with CXCL9 (β = 0.308, = 0.033). Furthermore, both total and HMW adiponectin were associated with C-reactive protein (β = 0.485, = 0.001; β = 0.463, = 0.001) and erythrocyte sedimentation rate (β = 0.442, = 0.001; β = 0.507, < 0.001). Leptin and resistin were not associated with plasma chemokines, markers of inflammation, or disease activity scores. Our study shows an association between circulating adiponectin and pro-inflammatory chemokines involved in RA pathogenesis as well as markers of inflammation in a well-characterized cohort of patients with untreated newly diagnosed RA.
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http://dx.doi.org/10.3390/biom11020325DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7924659PMC
February 2021

Neonatal gut colonization by is associated with higher childhood cytokine responses.

Gut Microbes 2020 11;12(1):1-14

Institute of Medicine, Department of Rheumatology and Inflammation Research, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.

The gut microbiota is a major stimulus for the immune system, and late acquisition of bacteria and/or reduced complexity of the gut flora may delay adaptive immune maturation. However, it is unknown how the gut bacterial colonization pattern in human infants is related to T cell activation during early childhood. We followed 65 Swedish children in the FARMFLORA cohort, from birth up to 3 years of age. In fecal samples collected at several time points during the first year of life, the gut colonization pattern was investigated with the use of both 16S rRNA next generation sequencing (NGS) and culture-based techniques. This was related to production of IL-13, IL-5, IL-6, TNF, IL-1β and IFN-γ by PHA-stimulated fresh mononuclear cells and to proportions of CD4 T cells that expressed CD45RO at 36 months of age. Both NGS and culture-based techniques showed that colonization by at 1 week of age associated with higher production of IL-5, IL-6, IL-13, TNF and IL-1β at 36 months of age. By contrast, gut colonization by or in early infancy related inversely to induced IL-13, IL-5 and TNF at 3 years of age. Infants with elder siblings produced more cytokines and had a larger fraction of CD45RO T cells compared to single children. However, controlling for these factors did not abolish the effect of colonization by on immune maturation. Thus, gut colonization in early infancy affects T cell maturation and may be especially prone to induce infantile immune maturation.
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http://dx.doi.org/10.1080/19490976.2020.1847628DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7747801PMC
November 2020

T helper cells in synovial fluid of patients with rheumatoid arthritis primarily have a Th1 and a CXCR3Th2 phenotype.

Arthritis Res Ther 2020 10 16;22(1):245. Epub 2020 Oct 16.

Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Box 480, 405 30, Gothenburg, Sweden.

Background: The majority of CD4 T helper (Th) cells found in the synovial fluid (SF) of patients with rheumatoid arthritis (RA) express CXCR3, a receptor associated with Th1 cells. In blood, subsets of Th2 and Th17 cells also express CXCR3, but it is unknown if these cells are present in RA SF or how cytokines from these subsets affect cytokine/chemokine secretion by fibroblast-like synoviocytes (FLS) from patients with RA.

Methods: We examined the proportions of Th1, Th2, CXCR3Th2, Th17, CXCR3Th17, Th1Th17, peripheral T helper (TPh) and T follicular helper (TFh) cells in paired SF and blood, as well as the phenotype of TPh and TFh cells in RA SF (n = 8), by the use of flow cytometry. We also examined the cytokine/chemokine profile in paired SF and plasma (n = 8) and in culture supernatants of FLS from patients with chronic RA (n = 7) stimulated with Th-associated cytokines, by the use of cytometric bead arrays and ELISA. Cytokine receptor expression in FLS (n = 3) were assessed by the use of RNA sequencing and qPCR.

Results: The proportions of Th1 and CXCR3Th2 cells were higher in SF than in blood (P < 0.05). TPh and PD-1TFh in RA SF were primarily of a Th1 and a CXCR3Th2 phenotype. Moreover, the levels of CXCL9, CXCL10, CCL20, CCL2, CXCL8, IL-6 and IL-10 were higher in SF than in plasma (P < 0.05). Lastly, IL-4, IL-13 and IL-17A induced RA FLS to secrete proinflammatory IL-6, CCL2, CXCL1 and CXCL8, while IFNγ mainly induced CXCL10.

Conclusion: These findings indicate that not only Th1 but also CXCR3Th2 cells may have a pathogenic role in RA synovial inflammation.
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http://dx.doi.org/10.1186/s13075-020-02349-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7566124PMC
October 2020

Polyunsaturated fatty acids in cod evoke chemotaxis and mobilize intracellular calcium in human eosinophils in part via FFAR4.

Allergy 2020 01 15;75(1):195-197. Epub 2019 Jul 15.

Department of Infectious Diseases, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

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http://dx.doi.org/10.1111/all.13955DOI Listing
January 2020

Sex-based differences in association between circulating T cell subsets and disease activity in untreated early rheumatoid arthritis patients.

Arthritis Res Ther 2018 07 20;20(1):150. Epub 2018 Jul 20.

Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy of University of Gothenburg, Box 480, S-405 30, Gothenburg, Sweden.

Background: It is not known if sex-based disparities in immunological factors contribute to the disease process in rheumatoid arthritis (RA). Hence, we examined whether circulating T cell subset proportions and their association with disease activity differed in male and female patients with untreated early rheumatoid arthritis (ueRA).

Methods: Proportions of T cell subsets were analyzed in peripheral blood from 72 ueRA DMARD- and corticosteroid-naïve patients (50 females and 22 males) and in 31 healthy age- and sex-matched controls. Broad analysis of helper and regulatory CD4 T cell subsets was done using flow cytometry. Disease activity in patients was assessed using DAS28, CDAI, swollen joint counts, tender joint counts, CRP, and ESR.

Results: Multivariate factor analyses showed that male and female ueRA patients display distinct profiles of association between disease activity and circulating T cell subset proportions. In male, but not female, ueRA patients Th2 cells showed a positive association with disease activity and correlated significantly with DAS28-ESR, CDAI, and swollen and tender joint counts. Likewise, proportions of non-regulatory CTLA-4 T cells associated positively with disease activity in male patients only, and correlated with DAS28-ESR. In contrast, there was a negative relation between Th1Th17 subset proportions and disease activity in males only. The proportions of Th17 cells correlated positively with DAS28-ESR in males only, while proportions of Th1 cells showed no relation to disease activity in either sex. There were no significant differences in proportions of T cell subsets between the sexes in patients with ueRA.

Conclusions: Our findings show sex-based differences in the association between T cell subsets and disease activity in ueRA patients, and that Th2 helper T cells may have a role in regulating disease activity in male patients.
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http://dx.doi.org/10.1186/s13075-018-1648-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6053769PMC
July 2018

Dihydrotestosterone levels at birth associate positively with higher proportions of circulating immature/naïve CD5 B cells in boys.

Sci Rep 2017 Nov 14;7(1):15503. Epub 2017 Nov 14.

Department of Rheumatology and Inflammation Research, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

Boys present with higher proportions of immature/naïve CD5 B cells than girls up to 3 years of age. Boys also have higher fractions of regulatory T cells (Tregs) in early infancy, but the mechanisms for these sex-related differences are unknown. In the prospective FARMFLORA follow-up study of 23 boys and 25 girls, we investigated if these immunological differences remained at 8 years of age. We also examined if testosterone or dihydrotestosterone (DHT) levels at birth and at 8 years of age were associated with immune maturation. Immunological variables and androgen levels were examined and measured in blood samples obtained at birth, 3-5 days and at 8 years of age. Boys had higher proportions of CD5 and immature/transitional CD24CD38 B cells, whereas girls had higher fractions of B cells with a memory phenotype at 8 years of age. School-aged boys also presented with higher frequencies of Tregs, and a greater capacity to produce T-cell-associated cytokines. Among boys, higher cord blood DHT levels were associated with higher proportions of CD5 B cells in early infancy and at 8 years of life. These results suggest that DHT actions in utero might be involved in the mechanism for delayed peripheral B-cell maturation in boys.
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http://dx.doi.org/10.1038/s41598-017-15836-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5686210PMC
November 2017

Regulatory Eosinophils Suppress T Cells Partly through Galectin-10.

J Immunol 2017 06 17;198(12):4672-4681. Epub 2017 May 17.

Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Göteborg SE-413 46, Sweden

Eosinophils have the capacity to regulate the function of T cell subsets. Our aim was to test the hypothesis of the existence of a regulatory subset of eosinophils. Human eosinophils were incubated with T cells that were stimulated with allogeneic leukocytes or CD3/CD28 cross-linking. After 2 d of coculture, 11% of the eosinophils gained CD16 expression. A CD16 subset of eosinophils, encompassing 1-5% of all eosinophils, was also identified in the blood of healthy subjects. FACS sorting showed that these CD16 eosinophils were significantly stronger suppressors of T cell proliferation than were conventional CD16 eosinophils. Human eosinophils contain stores of the immunoregulatory protein galectin-10. We found that Ab-mediated neutralization of galectin-10 partially abrogated the suppressive function of the eosinophils. Moreover, recombinant galectin-10 by itself was able to suppress T cell proliferation. Finally, we detected galectin-10-containing immune synapses between eosinophils and lymphocytes. To conclude, we describe a subset of suppressive eosinophils expressing CD16 that may escape detection because CD16-based negative selection is the standard procedure for the isolation of human eosinophils. Moreover, we show that galectin-10 functions as a T cell-suppressive molecule in eosinophils.
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http://dx.doi.org/10.4049/jimmunol.1601005DOI Listing
June 2017

Blood chemokine profile in untreated early rheumatoid arthritis: CXCL10 as a disease activity marker.

Arthritis Res Ther 2017 Feb 2;19(1):20. Epub 2017 Feb 2.

Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy of University of Gothenburg, Box 480, S-405 30, Gothenburg, Sweden.

Background: We have recently analyzed the profile of T-cell subtypes based on chemokine receptor expression in blood from untreated early rheumatoid arthritis (ueRA) patients compared to healthy controls (HC). Here, we compared the levels of the respective chemokines in blood plasma of ueRA patients with those of HC. We also studied the association of chemokine levels with the proportions of circulating T-cell subsets and the clinical disease activity.

Methods: Peripheral blood was obtained from 43 patients with ueRA satisfying the ACR 2010 criteria and who had not received any disease-modifying anti-rheumatic drugs (DMARD) or prednisolone, and from 14 sex- and age-matched HC. Proportions of T helper cells in blood, including Th0, Th1, Th2, Th17, Th1Th17, TFh, and regulatory T cells, were defined by flow cytometry. Fifteen chemokines, including several CXCL and CCL chemokines related to the T-cell subtypes as well as to other major immune cells, were measured in blood plasma using flow cytometry bead-based immunoassay or ELISA. Clinical disease activity in patients was evaluated by assessing the following parameters: Disease Activity Score in 28 joints (DAS28), Clinical Disease Activity Index (CDAI), swollen joint counts (SJC), tender joint counts (TJC), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR). The data were analyzed using multivariate factor analyses followed by univariate analyses.

Results: Multivariate discriminant analysis showed that patients with ueRA were separated from HC based on the blood plasma chemokine profile. The best discriminators were CXCL9, CXCL10, CXCL13, CCL4, and CCL22, which were significantly higher in ueRA compared to HC in univariate analyses. Among the chemokines analyzed, only CXCL10 correlated with multiple disease activity measures, including DAS28-CRP, DAS28-ESR, CDAI, SJC in 66 joints, CRP, and ESR.

Conclusions: High circulating levels of CXCL10 in the plasma of ueRA patients and the association with the clinical disease activity suggests that CXCL10 may serve as a disease activity marker in early rheumatoid arthritis.
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http://dx.doi.org/10.1186/s13075-017-1224-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5289001PMC
February 2017

IFN type I and II induce BAFF secretion from human decidual stromal cells.

Sci Rep 2017 01 6;7:39904. Epub 2017 Jan 6.

Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden.

B cell activating factor (BAFF) is a critical cytokine for maturation of immature B cells. In murine lymph nodes, BAFF is mainly produced by podoplanin-expressing stromal cells. We have previously shown that circulating BAFF levels are maximal at birth, and that farmers' children exhibit higher BAFF levels in cord blood than non-farmers' children. Here, we sought to investigate whether maternal-derived decidual stromal cells from placenta secrete BAFF and examine what factors could stimulate this production. We found that podoplanin is expressed in decidua basalis and in the underlying villous tissue as well as on isolated maternal-derived decidual stromal cells. Decidual stromal cells produced BAFF when stimulated with IFN-γ and IFN-α, and NK cells and NK-T-like cells competent of IFN-γ production were isolated from the decidua. Finally, B cells at different maturational stages are present in decidua and all expressed BAFF-R, while stromal cells did not. These findings suggest that decidual stromal cells are a cellular source of BAFF for B cells present in decidua during pregnancy.
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http://dx.doi.org/10.1038/srep39904DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5216379PMC
January 2017

Earlier infantile immune maturation is related to higher DTP vaccine responses in children.

Clin Transl Immunology 2016 Mar 11;5(3):e65. Epub 2016 Mar 11.

Department of Rheumatology and Inflammation Research, Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg , Gothenburg, Sweden.

There are large inter-individual variations in vaccine-specific antibody responses in children. We sought to investigate whether early-life environmental factors and/or adaptive immune maturation were related to diphtheria-tetanus-pertussis (DTP) vaccine-specific antibody levels at 18 months of age. In the prospective FARMFLORA birth-cohort, including both farming and non-farming families, children were immunized with DTP vaccine at 3, 5 and 12 months of age. DTP vaccine-induced antibody levels were measured in plasma at 18 months of age. Infants' blood samples obtained at birth, 3-5 days, 4, 18 and 36 months and at 8 years of age were analyzed for total CD4(+) T- and B-cell counts, proportions of naïve and memory T and B cells, and fractions of putative regulatory T cells by flow cytometry. Multivariate factor analysis was used to examine associations between immune variables and vaccine responses. The most apparent multivariate pattern was that higher anti-DTP antibody titers at 18 months of age were associated with lower infantile total counts of T and B cells in the blood. Furthermore, lower infantile total T- and B-cell blood counts were associated with higher proportions of circulating CD45RO(+) memory T cells and to lower proportions of α4β7(+) naïve T cells later in childhood. The multivariate findings were corroborated in univariate correlation analyses. Sex, delivery mode and dairy farm exposure were unrelated to the magnitude of DTP-specific antibody responses. Our results thus suggest that children with a more mature/activated infantile adaptive immunity respond with higher vaccine-induced anti-DTP antibody levels at 18 months of age.
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http://dx.doi.org/10.1038/cti.2016.7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4815027PMC
March 2016

Delayed adaptive immunity is related to higher MMR vaccine-induced antibody titers in children.

Clin Transl Immunology 2016 Apr 29;5(4):e75. Epub 2016 Apr 29.

Department of Rheumatology and Inflammation Research at the Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg , Gothenburg, Sweden.

There are notable inter-individual variations in vaccine-specific antibody responses in vaccinated children. The aim of our study was to investigate whether early-life environmental factors and adaptive immune maturation prior and close to measles-mumps-rubella (MMR) immunization relate to magnitudes of vaccine-specific antibody titers. In the FARMFLORA birth cohort, including both farming and non-farming families, children were immunized with the MMR vaccine at 18 months of age. MMR vaccine-induced antibody titers were measured in plasma samples obtained at 36 months of age. Infants' blood samples obtained at birth, 3-5 days and at 4 and 18 months of age were analyzed for T- and B-cell numbers, proportions of naive and memory T and B cells, and fractions of putative regulatory T cells. Multivariate factor analyses show that higher anti-MMR antibody titers were associated with a lower degree of adaptive immune maturation, that is, lower proportions of memory T cells and a lower capacity of mononuclear cells to produce cytokines, but with higher proportions of putative regulatory T cells. Further, children born by cesarean section (CS) had significantly higher anti-measles titers than vaginally-born children; and CS was found to be associated with delayed adaptive immunity. Also, girls presented with significantly higher anti-mumps and anti-rubella antibody levels than boys at 36 months of age. These results indicate that delayed adaptive immune maturation before and in close proximity to immunization seems to be advantageous for the ability of children to respond with higher anti-MMR antibody levels after vaccination.
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http://dx.doi.org/10.1038/cti.2016.20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4855269PMC
April 2016

Circulating T helper and T regulatory subsets in untreated early rheumatoid arthritis and healthy control subjects.

J Leukoc Biol 2016 10 17;100(4):823-833. Epub 2016 May 17.

Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

The pathogenic role and frequency of T cell subtypes in early rheumatoid arthritis are still unclear. We therefore performed a comprehensive analysis of the circulating T cell subtype pattern in patients with untreated early rheumatoid arthritis compared to healthy control subjects. Peripheral blood mononuclear cells were obtained from 26 patients with untreated early rheumatoid arthritis and from with 18 age- and sex-matched healthy control subjects. T helper cell types Th0, Th1, Th2, Th17, and Th1/17 and nonclassic T helper subsets were defined by flow cytometry based on the expression of chemokine receptors CCR4, CCR6, and CXCR3. Regulatory T cells were defined by expression of CD25 CD127 and also FOXP3 CXCR5 cells among regulatory and nonregulatory T cells were defined as T follicular regulatory and T follicular helper cells, respectively. The phenotype of T cell subsets was confirmed by transcription factor and cytokine secretion analyses. Multivariate discriminant analysis showed that patients with untreated early rheumatoid arthritis were segregated from healthy control subjects based on the circulating T cell subset profile. Among the discriminator subsets, CCR4CXCR3 (Th2 and Th17), CTLA4 and FOXP3 subsets were present in significantly higher frequencies, whereas CCR4 (Th1/Th17, CCR6CCR4CXCR3, and Th1) subsets were present in lower frequencies in patients with untreated early rheumatoid arthritis compared with healthy control subjects. The proportions of Th2 and Th17 subsets associated positively with each other and negatively with the CXCR3/interferon γ-secreting subsets (Th1 and Th1/Th17) in patients with untreated rheumatoid arthritis. The proportions of Th2 cells increased with age in patients with untreated early rheumatoid arthritis and healthy control subjects. The dominance of circulating CCR4CXCR3 T helper subsets (Th2 and Th17) in untreated early rheumatoid arthritis point toward a pathogenic role of these cells in early stages of the disease.
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http://dx.doi.org/10.1189/jlb.5A0116-025RDOI Listing
October 2016

Parents' experiences of their child's return to school following acquired brain injury (ABI): A systematic review of qualitative studies.

Brain Inj 2016 8;30(7):829-38. Epub 2016 Apr 8.

a Disability and Community Inclusion, School of Health Sciences , Flinders University , Adelaide , Australia.

Objective: To examine parents' experiences during their child's return to school following ABI.

Research Design: Systematic literature review.

Methods: Six electronic databases relevant to the fields of brain injury and education were searched between 1980-2015. In addition, two qualitative journals and references from articles were hand-searched for further literature. Search results were screened independently by two reviewers for relevance. Studies meeting the inclusion criteria were analysed using the McMasters Critical Review Form for Qualitative Studies.

Results: Two hundred and sixteen articles were screened after duplicates had been removed and 11 were assessed for relevance, resulting in six full text articles for review. The quality of studies was mixed, with only two presenting a high number of quality indicators for qualitative research. Ten themes were identified and grouped into three clusters: influencing factors (environment, school, parent and child factors); features of interaction (information, communication and collaboration); and quality levels of outcome (conflict, coping and construction of new roles and identities).

Conclusions: Parents' experiences are influenced by the quality of information, communication and collaboration between the school, health professionals and the family. Further well designed qualitative studies examining parents' experiences and support needs are required.
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http://dx.doi.org/10.3109/02699052.2016.1146963DOI Listing
January 2018

APLP1 as a cerebrospinal fluid biomarker for γ-secretase modulator treatment.

Alzheimers Res Ther 2015 Dec 22;7(1):77. Epub 2015 Dec 22.

Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at the University of Gothenburg, Sahlgrenska University Hospital, Mölndal, S-431 80, Sweden.

Introduction: Alzheimer's disease brains are characterized by extracellular plaques containing the aggregated amyloid β42 (Aβ42) peptide and intraneuronal tangles containing hyperphosphorylated tau. Aβ42 is produced by sequential processing of the amyloid precursor protein (APP) by β-secretase followed by γ-secretase. Substantial efforts have been put into developing pharmaceuticals preventing the production or increasing the clearance of Aβ42. However, treatments inhibiting γ-secretase have proven disappointing due to off-target effects. To circumvent these effects, γ-secretase modulators (GSMs) have been developed, which rather than inhibiting γ-secretase shift its preference into producing less aggregation-prone shorter Aβ peptides. Belonging to the same family of proteins as APP, amyloid-like protein 1 (APLP1) is also a substrate for γ-secretase. Herein we investigated whether the GSM E2012 affects APLP1 processing in the central nervous system by measuring APLP1 peptide levels in cerebrospinal fluid (CSF) before and after E2012 treatment in dogs.

Methods: An in-house monoclonal APLP1 antibody, AP1, was produced and utilized for immunopurification of APLP1 from human and dog CSF in a hybrid immuno-affinity mass spectrometric method. Seven dogs received a single dose of 20 or 80 mg/kg of E2012 in a randomized cross-over design and CSF was collected prior to and 4, 8 and 24 hours after dosing.

Results: We have identified 14 CSF APLP1 peptides in humans and 12 CSF APLP1 peptides in dogs. Of these, seven were reproducibly detectable in dogs who received E2012. We found a dose-dependent relative increase of the CSF peptides APLP1β17, 1β18 and 1β28 accompanied with a decrease of 1β25 and 1β27 in response to E2012 treatment. All peptides reverted to baseline over the time of sample collection.

Conclusion: We show an in vivo effect of the GSM E2012 on the processing of APLP1 which is measurable in CSF. These data suggest that APLP1 peptides may be used as biomarkers to monitor drug effects of GSMs on γ-secretase processing in clinical trials. However, this requires further investigation in larger cohorts, including studies in man.
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http://dx.doi.org/10.1186/s13195-015-0160-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4687145PMC
December 2015

C-terminal neurogranin is increased in cerebrospinal fluid but unchanged in plasma in Alzheimer's disease.

Alzheimers Dement 2015 Dec 16;11(12):1461-1469. Epub 2015 Jun 16.

Department of Research, ADx NeuroSciences, Ghent, Belgium. Electronic address:

Introduction: Biomarkers monitoring synaptic degeneration/loss would be valuable for Alzheimer's disease (AD) diagnosis. Postsynaptic protein neurogranin may be a promising cerebrospinal fluid (CSF) biomarker but has not yet been evaluated as a plasma biomarker.

Methods: Using an in-house designed prototype enzyme-linked immunosorbent assay (ELISA) targeting neurogranin C-terminally, we studied neurogranin in paired CSF/plasma samples of controls (n = 29) versus patients experiencing MCI, or dementia, due to AD (in total n = 59).

Results: CSF neurogranin was increased in AD and positively correlated with CSF tau, whereas there was a negative relationship between CSF neurogranin (and tau) and CSF Aβ1-42/Aβ1-40. No differences were detected in plasma neurogranin between controls and AD. Also, there was no correlation between CSF and plasma neurogranin, excluding confounding effects of the latter.

Discussion: This study strengthens the potential of neurogranin as an AD CSF biomarker, which now needs validation in larger studies. As tools, straightforward immunoassays can be used, as demonstrated by the described ELISA.
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http://dx.doi.org/10.1016/j.jalz.2015.05.012DOI Listing
December 2015

Cerebrospinal fluid levels of the synaptic protein neurogranin correlates with cognitive decline in prodromal Alzheimer's disease.

Alzheimers Dement 2015 Oct 19;11(10):1180-90. Epub 2014 Dec 19.

Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden. Electronic address:

Introduction: Synaptic dysfunction is an early event in Alzheimer's disease (AD) pathogenesis and directly related to cognitive impairment. Consequently, synaptic biomarkers may be valuable tools for both early diagnosis and disease stage. Neurogranin (Ng) is a postsynaptic protein involved in memory consolidation.

Methods: We developed three monoclonal anti-Ng antibodies. Mass spectrometry and a novel enzyme-linked immunosorbent assay were used to analyze cerebrospinal fluid (CSF) Ng in three independent clinical cohorts including patients with AD dementia (n = 100 in total), mild cognitive impairment patients (MCI), (n = 40) and controls (n = 80 in total).

Results: We show in three independent clinical cohorts a marked increase in CSF Ng levels in AD dementia (P < .001 in all studies). In addition, high CSF Ng levels at the MCI stage predicted progression to dementia due to AD with a hazard ratio of 12.8 (95% confidence interval 1.6-103.0, P = .02). In amyloid-positive MCI patients, high CSF Ng correlated with a more rapid change in cognition during clinical follow-up (P = .03).

Discussion: These results suggest that CSF Ng is a novel AD biomarker that may be used to monitor synaptic degeneration, and correlates with the rate of cognitive decline in prodromal AD.
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http://dx.doi.org/10.1016/j.jalz.2014.10.009DOI Listing
October 2015

Eosinophils from hematopoietic stem cell recipients suppress allogeneic T cell proliferation.

Biol Blood Marrow Transplant 2014 Dec 28;20(12):1891-8. Epub 2014 Aug 28.

Department of Infectious Diseases, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

Eosinophilia has been associated with less severe graft-versus-host disease (GVHD), but the underlying mechanism is unknown. We hypothesized that eosinophils diminish allogeneic T cell activation in patients with chronic GVHD. The capacity of eosinophils derived from healthy subjects and hematopoietic stem cell (HSC) transplant recipients, with or without chronic GVHD, to reduce allogeneic T cell proliferation was evaluated using a mixed leukocyte reaction. Eosinophil-mediated inhibition of proliferation was observed for the eosinophils of both healthy subjects and patients who underwent HSC transplantation. Eosinophils from patients with and without chronic GVHD were equally suppressive. Healthy eosinophils required cell-to-cell contact for their suppressive capacity, which was directed against CD4(+) T cells and CD8(+) T cells. Neither eosinophilic cationic protein, eosinophil-derived neurotoxin, indoleamine 2,3-dioxygenase, or increased numbers of regulatory T cells could account for the suppressive effect of healthy eosinophils. Real-time quantitative PCR analysis revealed significantly increased mRNA levels of the immunoregulatory protein galectin-10 in the eosinophils of both chronic GVHD patients and patients without GVHD, as compared with those from healthy subjects. The upregulation of galectin-10 expression in eosinophils from patients suggests a stimulatory effect of HSC transplantation in itself on eosinophilic galectin-10 expression, regardless of chronic GVHD status. To conclude, eosinophils from HSC transplant recipients and healthy subjects have a T cell suppressive capacity.
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http://dx.doi.org/10.1016/j.bbmt.2014.08.017DOI Listing
December 2014

Staphylococcus aureus convert neonatal conventional CD4(+) T cells into FOXP3(+) CD25(+) CD127(low) T cells via the PD-1/PD-L1 axis.

Immunology 2014 Mar;141(3):467-81

Department of Rheumatology and Inflammation Research, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.

The gut microbiota provides an important stimulus for the induction of regulatory T (Treg) cells in mice, whether this applies to newborn children is unknown. In Swedish children, Staphylococcus aureus has become a common early colonizer of the gut. Here, we sought to study the effects of bacterial stimulation on neonatal CD4(+) T cells for the induction of CD25(+) CD127(low) Treg cells in vitro. The proportion of circulating CD25(+) CD127(low) Treg cells and their expression of FOXP3, Helios and CTLA-4 was examined in newborns and adults. To evaluate if commensal gut bacteria could induce Treg cells, CellTrace violet-stained non-Treg cells from cord or peripheral blood from adults were co-cultured with autologous CD25(+) CD127(low) Treg cells and remaining mononuclear cells and stimulated with S. aureus. Newborns had a significantly lower proportion of CD25(+) CD127(low) Treg cells than adults, but these cells were Helios(+) and CTLA-4(+) to a higher extent than in adults. FOXP3(+) CD25(+) CD127(low) T cells were induced mainly in neonatal CellTrace-stained non-Treg cells after stimulation with S. aureus. In cell cultures from adults, S. aureus induced CD25(+) CD127(low) T cells only if sorted naive CD45RA(+) non-Treg cells were used, but these cells expressed less FOXP3 than those induced from newborns. Sorted neonatal CD25(+) CD127(low) T cells from S. aureus-stimulated cultures were still suppressive. Finally, blocking PD-L1 during stimulation reduced the induction of FOXP3(+) CD25(+) CD127(low) T cells. These results suggest that newborns have a higher proportion of circulating thymically derived Helios(+) Treg cells than adults and that S. aureus possess an ability to convert neonatal conventional CD4(+) T cells into FOXP3(+) CD25(+) CD127(low) Treg cells via the PD-1/PD-L1 axis.
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http://dx.doi.org/10.1111/imm.12209DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3930383PMC
March 2014

Sensitization to Cor a 9 and Cor a 14 is highly specific for a hazelnut allergy with objective symptoms in Dutch children and adults.

J Allergy Clin Immunol 2013 Aug 10;132(2):393-9. Epub 2013 Apr 10.

Department of Dermatology/Allergology, University Medical Center Utrecht, Utrecht, The Netherlands.

Background: Component-resolved diagnosis has been shown to improve the diagnosis of food allergy.

Objective: We sought to evaluate whether component-resolved diagnosis might help to identify patients at risk of objective allergic reactions to hazelnut.

Method: A total of 161 hazelnut-sensitized patients were included: 40 children and 15 adults with objective symptoms on double-blind, placebo-controlled food challenges (DBPCFCs) and 24 adults with a convincing objective history were compared with 41 children and 41 adults with no or subjective symptoms on DBPCFCs (grouped together). IgE levels to hazelnut extract and single components were analyzed with ImmunoCAP.

Results: IgE levels to hazelnut extract were significantly higher in children with objective than with no or subjective symptoms. In 13% of children and 49% of adults with hazelnut allergy with objective symptoms, only sensitization to rCor a 1.04 was observed and not to other water-soluble allergens. Sensitization to rCor a 8 was rare, which is in contrast to rCor a 1. Sensitization to nCor a 9, rCor a 14, or both was strongly associated with hazelnut allergy with objective symptoms. By using adapted cutoff levels, a diagnostic discrimination between severity groups was obtained. IgE levels to either nCor a 9 of 1 kUA/L or greater or rCor a 14 of 5 kUA/L or greater (children) and IgE levels to either nCor a 9 of 1 kUA/L or greater or rCor a 14 of 1 kUA/L or greater (adults) had a specificity of greater than 90% and accounted for 83% of children and 44% of adults with hazelnut allergy with objective symptoms.

Conclusion: Sensitization to Cor a 9 and Cor a 14 is highly specific for patients with objective symptoms in DBPCFCs as a marker for a more severe hazelnut allergic phenotype.
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http://dx.doi.org/10.1016/j.jaci.2013.02.024DOI Listing
August 2013

Higher proportions of circulating FOXP3+ and CTLA-4+ regulatory T cells are associated with lower fractions of memory CD4+ T cells in infants.

J Leukoc Biol 2011 Dec 20;90(6):1133-40. Epub 2011 Sep 20.

Departments of Rheumatology and Inflammation Research, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.

In adults, a majority of FOXP3(+) T(regs) expresses CTLA-4, and this costimulatory molecule is essential to control the expansion of other T cells. However, it remains to be investigated whether FOXP3(+) and/or CTLA-4(+) T(regs) are associated with the expression of memory markers and homing receptors on CD4(+) T cells. Thus, in a prospective newborn-infant cohort study, we examined the proportions of FOXP3(+) and CTLA-4(+) T(regs) within the CD4(+)CD25(+) T cell population and the fractions of CD4(+) T cells that expressed CD45RA, CD45RO, HLA-DR, α(4)β(7), CD62L, and CCR4 at several time-points during the first 3 years of life using flow cytometry. With the use of multivariate factor analysis, we found that a high proportion of FOXP3(+) or CTLA-4(+) T(regs) during the first 18 months of life was associated positively with the fraction of T cells that expressed a naïve phenotype (CD45RA and α(4)β(7)) and inversely related to the fraction of T cells that expressed a memory phenotype (CD45RO and CCR4) later in childhood. In conclusion, FOXP3(+) or CTLA-4(+) T(regs) may modulate CD4(+) T cell activation and homing receptor expression in children.
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http://dx.doi.org/10.1189/jlb.0511244DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3236549PMC
December 2011

Identification of novel α-synuclein isoforms in human brain tissue by using an online nanoLC-ESI-FTICR-MS method.

Neurochem Res 2011 Nov 16;36(11):2029-42. Epub 2011 Jun 16.

Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital, S-43180 Mölndal, Sweden.

Parkinson's disease (PD) and Dementia with Lewy bodies (DLB) are neurodegenerative diseases that are characterized by intra-neuronal inclusions of Lewy bodies in distinct brain regions. These inclusions consist mainly of aggregated α-synuclein (α-syn) protein. The present study used immunoprecipitation combined with nanoflow liquid chromatography (LC) coupled to high resolution electrospray ionization Fourier transform ion cyclotron resonance tandem mass spectrometry (ESI-FTICR-MS/MS) to determine known and novel isoforms of α-syn in brain tissue homogenates. N-terminally acetylated full-length α-syn (Ac-α-syn₁₋₁₄₀) and two N-terminally acetylated C-terminally truncated forms of α-syn (Ac-α-syn₁₋₁₃₉ and Ac-α-syn₁₋₁₀₃) were found. The different forms of α-syn were further studied by Western blotting in brain tissue homogenates from the temporal cortex Brodmann area 36 (BA36) and the dorsolateral prefrontal cortex BA9 derived from controls, patients with DLB and PD with dementia (PDD). Quantification of α-syn in each brain tissue fraction was performed using a novel enzyme-linked immunosorbent assay (ELISA).
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http://dx.doi.org/10.1007/s11064-011-0527-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3183298PMC
November 2011

Development of gut-homing receptors on circulating B cells during infancy.

Clin Immunol 2011 Jan 13;138(1):97-106. Epub 2010 Nov 13.

Department of Rheumatology and Inflammation Research, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.

B cell gut-homing is mainly mediated by α4β7, CCR9 and CCR10. We here studied the expression of these receptors on B cells from cord blood and from peripheral blood at 1, 4, 18 and 36 months of age in a prospective cohort of Swedish infants. The proportion of all B cells expressing α4β7 as well as the fraction of CCR10+ B cells expressing α4β7 was highest in early infancy. Nearly all naïve B cells in all age groups expressed α4β7, whereas the expression on class-switched B cells decreased with age. Moreover, the proportion of both IgA+ and IgG+ B cells expressing α4β7, CCR9 and CCR10 were higher during the first months when compared to adults. In conclusion, the high fraction of circulating IgA+ and IgG+ B cells expressing CCR9 and CCR10 in the first months of life indicates activation of naïve B cells in the gut, coinciding with bacterial colonization.
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http://dx.doi.org/10.1016/j.clim.2010.10.003DOI Listing
January 2011

Randomized phase II study of gemcitabine and carboplatin +/- sequential docetaxel in non-small cell lung cancer.

Lung Cancer 2011 Feb 23;71(2):178-81. Epub 2010 May 23.

Department of Pulmonary Medicine and Allergy, Karolinska University Hospital, SE-171 76 Stockholm, Sweden.

Sequential administration of chemotherapeutic drugs might have advantages: additive toxicity is avoided and the individual drugs can be given in full dosages. The Swedish group earlier found the combination of gemcitabine and carboplatin to be effective and with acceptable toxicity. The group therefore decided to add docetaxel in a sequential way in a randomized phase II study. Patients were randomized to either gemcitabine or carboplatin for six cycles or the same regimen for three cycles followed by weekly single agent docetaxel. The primary objective was time to progression (TTP). One hundred and twenty-three patients with performance status WHO 0-2 and with earlier un-treated non-small cell lung cancer with measurable stage IIIB disease, not amenable to curative treatment, or stage IV disease without known metastatic spread to the CNS, were enrolled. Hematological toxicity was more common in the GC group but clinically significant bleeding or leucopenic fever occurred only in a minority of patients. No complete responses were noted. Partial response (PR) was observed in 19.3% and 20.8% in the GC and GCD group, respectively. Progression-free survival was 5.6 and 4.8 months and overall survival time 10.6 and 10.1 months in the GC and GCD groups, respectively. Thus, sequential treatment with docetaxel after treatment with gemcitabine and carboplatin did not improve time to progression, response rates, or overall survival.
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http://dx.doi.org/10.1016/j.lungcan.2010.05.007DOI Listing
February 2011

Age-related changes of muscle and plasma amino acids in healthy children.

Amino Acids 2010 Jul 20;39(2):359-66. Epub 2009 Dec 20.

Department of Surgery, Gastrocentrum, K53, Karolinska University Hospital, 141 86, Stockholm, Sweden.

The aim of the study was to explore if changes in muscle and plasma amino acid concentrations developed during growth and differed from levels seen in adults. The gradient and concentrations of free amino acids in muscle and plasma were investigated in relation to age in metabolic healthy children. Plasma and specimens from the abdominal muscle were obtained during elective surgery. The children were grouped into three groups (group 1: < 1 year, n = 8; group 2: 1-4 years, n = 13 and group 3: 5-15 years, n = 15). A reference group of healthy adults (21-38 years, n = 22) was included in their comparisons and reflected specific differences between children and adults. In muscle the concentrations of 8 out of 19 amino acids analysed increased with age, namely taurine, aspartate, threonine, alanine, valine, isoleucine, leucine, histidine, as well as the total sums of branched chain amino acids (BCAA), basic amino acids (BAA) and total sum of amino acids (P < 0.05). In plasma the concentrations of threonine, glutamine, valine, cysteine, methionine, leucine, lysine, tryptophane, arginine, BCAA, BAA and the essential amino acids correlated with age (P < 0.05). These results indicate that there is an age dependency of the amino acid pattern in skeletal muscle and plasma during growth.
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http://dx.doi.org/10.1007/s00726-009-0446-1DOI Listing
July 2010

Component-resolved in vitro diagnosis of hazelnut allergy in Europe.

J Allergy Clin Immunol 2009 May 2;123(5):1134-41, 1141.e1-3. Epub 2009 Apr 2.

Allergy Clinic, National University Hospital, Copenhagen, Denmark.

Background: Food allergy to hazelnut occurs both with and without concomitant pollen allergy.

Objective: We sought to evaluate a panel of hazelnut allergens for diagnosis of hazelnut allergy in Spain, Switzerland, and Denmark.

Methods: Fifty-two patients with a positive double-blind, placebo-controlled food challenge result with hazelnuts; 5 patients with a history of anaphylaxis; 62 patients with pollen allergy but hazelnut tolerance; and 63 nonatopic control subjects were included. Serum IgE levels to hazelnut extract, recombinant hazelnut allergens (rCor a 1.04, rCor a 2, rCor a 8, rCor a 11), and native allergens (nCor a 9, nCor a Bd8K, nCor a Bd11K) were analyzed by means of ImmunoCAP.

Results: Among patients with hazelnut allergy, 91% (Switzerland/Spain, 100%; Denmark, 75%) had IgE to hazelnut extract, 75% to rCor a 1.04, 42% to rCor a 2, 28% to rCor a 8, and 2% to rCor a 11. The highest rate of sensitization to Cor a 1.04 was found in the northern regions (Switzerland/Denmark, 100%; Spain, 18%), whereas IgE to the lipid transfer protein rCor a 8 prevailed in Spain (Spain, 71%; Switzerland, 15%; Denmark, 5%). IgE to profilin rCor a 2 was equally distributed (40% to 45%). Among control subjects with pollen allergy, 61% had IgE to hazelnut extract, 69% to rCor a 1.04, 34% to rCor a 2, 10% to rCor a 8, and 6% to rCor a 11.

Conclusion: Component-resolved in vitro analyses revealed substantial differences in IgE profiles of hazelnut allergic and hazelnut tolerant patients across Europe.
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http://dx.doi.org/10.1016/j.jaci.2009.02.005DOI Listing
May 2009

CC16 inhibits the migration of eosinophils towards the formyl peptide fMLF but not towards PGD2.

Inflammation 2009 Apr;32(2):65-9

Department of Rheumatology and Inflammation Research, Sahlgrenska Academy, University of Gothenburg, Guldhedsgatan 10A, 413 46, Göteborg, Sweden.

Clara cell 16-kDa (CC16) is an anti-inflammatory protein chiefly produced in the lung epithelium. CC16 has been shown to inhibit the migration of rabbit neutrophils and human monocytes toward the formyl peptide N-formyl-methionine-leucin-phenylalanin (fMLF). Eosinophils migrate towards prostaglandin D2 (PGD(2)) and CC16 has been shown to bind to PGD(2). Therefore we investigated if CC16 could inhibit the migration of human eosinophils and neutrophils towards fMLF and/or PGD(2). Migration of eosinophils and neutrophils was assessed in a microplate migration system using specific ligands and receptor antagonists. CC16 inhibited the migration of eosinophils and neutrophils toward fMLF, which is likely to result from the interaction of CC16 with members of the formyl-peptide receptor family. However, CC16 did not inhibit eosinophil migration towards PGD(2). We therefore propose that CC16 may down-modulate the entry of human eosinophils and neutrophils into the airways during inflammation in the lung.
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http://dx.doi.org/10.1007/s10753-008-9103-1DOI Listing
April 2009

Preexisting antibodies to homologous colonization factors and heat-labile toxin in serum, and the risk to develop enterotoxigenic Escherichia coli-associated diarrhea.

Diagn Microbiol Infect Dis 2008 Feb 25;60(2):229-31. Epub 2007 Oct 25.

Institute of Biomedicine, Department of Microbiology and Immunology, The Sahlgrenska Academy of Göteborg University, S-40530 Göteborg, Sweden.

Preexisting serum immunoglobulin (Ig) A and IgG titers against colonization factors and heat-labile toxin of enterotoxigenic Escherichia coli (ETEC) were examined in young adults who subsequently developed ETEC-associated diarrhea and in healthy matched controls. The data suggest an inverse association between the antibody titers against colonization factors, but not heat-labile toxin, and development of ETEC-associated diarrhea.
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http://dx.doi.org/10.1016/j.diagmicrobio.2007.09.010DOI Listing
February 2008

Soluble CD14 and CD83 from human neonatal antigen-presenting cells are inducible by commensal bacteria and suppress allergen-induced human neonatal Th2 differentiation.

Infect Immun 2007 Aug 25;75(8):4097-104. Epub 2007 May 25.

Department of Rheumatology and Inflammation Research, Göteborg University, Guldhedsgatan 10, 413 46 Göteborg, Sweden.

CD14 is expressed on the cell surface of various antigen-presenting cells, and CD83 is a maturation marker for dendritic cells (DC). CD14 and CD83 are also present as soluble proteins, and both have immunoregulatory functions. We examined whether neonatal cord blood monocytes or DC released soluble CD14 (sCD14) or sCD83 when exposed to the commensal intestinal bacteria Clostridium perfringens, Staphylococcus aureus, Lactobacillus rhamnosus, Escherichia coli, and Bacteroides fragilis. We found that the gram-positive bacteria C. perfringens and S. aureus, but not gram-negative bacteria, induced the release of sCD14 from monocytes. DC, on the other hand, released sCD14 in response to both gram-positive and gram-negative bacteria. Moreover, the expression of the virulence factor staphylococcal protein A seemed to be important for S. aureus-induced sCD14 production from both monocytes and DC. Soluble CD83 was released from DC, but not from monocytes, when exposed to both gram-positive and gram-negative bacteria. Finally, to investigate whether sCD14 or sCD83 could modulate neonatal allergen-induced T-cell differentiation, DC were exposed to birch allergen alone or in the presence of sCD14 or sCD83 and then cocultured with autologous T cells. We demonstrate that sCD14 and sCD83 inhibited the birch allergen-induced Th2 differentiation by suppressing interleukin 13 production. Together, these results suggest that the commensal intestinal flora may be an important stimulus for the developing immune system by inducing the immunoregulatory proteins sCD14 and sCD83, which may be involved in preventing T-cell sensitization to allergens in infants.
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http://dx.doi.org/10.1128/IAI.01744-06DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1952007PMC
August 2007

The district nurse's perceptions of elderly patients' oral health: a qualitative interview study.

Acta Odontol Scand 2007 Jun;65(3):177-82

Department of Geriatric Dentistry, Institution of Odontology, Karolinska Institutet, Stockholm, Sweden.

Objective: The aim of this qualitative study based on interviews was to explore the perceptions that district nurses have of the oral health of elderly patients.

Material And Methods: The criterion for inclusion was being a district nurse working in a primary health-care centre in the County of Stockholm. The respondents were asked open-ended questions about their perceptions of oral health and about the impact of oral problems on the general health and well-being of elderly patients. The analyses started at the first interview and proceeded in parallel until no further relevant information could be obtained. Analysis of the open-ended questions was inspired by grounded theory methodology and comprised four stages: native reading, open coding, axial coding, and selective coding.

Results: The one core category identified, namely indistinct professional duties of the district nurse, formed the central meaning of the district nurse's perceptions of oral health in elderly patients. This related to two other categories labelled 'insights into the district nurse's professional role' and 'obstacles for the district nurse', with sub-categories.

Conclusion: Although the district nurses in this study were aware of the impact of oral health in old age, their attitude was that this was a matter for dentistry.
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http://dx.doi.org/10.1080/00016350701278898DOI Listing
June 2007

'Oral health is not my department'. Perceptions of elderly patients' oral health by general medical practitioners in primary health care centres: a qualitative interview study.

Scand J Caring Sci 2007 Mar;21(1):126-33

Department of Periodontology, Institution of Odontology, Karolinska Institutet, Stockholm, Sweden.

The purpose of this study was to explore general medical practitioners' (GPs) perceptions of the oral health of their elderly patients. The design was a qualitative study based on individual in-depth interviews with GPs. The criterion for inclusion in the study was that the GP was a specialist in family medicine working in a primary health care centre (PHCC:s) in the county of Stockholm. The participants took part in the study after informed consent. Eleven GPs were interviewed. The interview started with semi-structured questions about the respondents' clinical presentation of their elderly patients', e.g. medication, medical treatment and socioeconomic status. The interview concluded with questions about the respondents' experiences of and perceptions of the oral health of their patients. This process started with the first interview and proceeded with successive interviews until no new relevant information was forthcoming. The initial semi-structured part of the interview guide was analysed for content with special reference to descriptive answers. The final open questions were analysed by a method inspired by grounded theory (GT) and comprised three stages: open coding, axial coding and selective coding. In the GT influenced analysis process, three categories, health perspective, working conditions and cultural differences, each in turn containing subcategories, were identified and labelled. The most significant category, cultural differences, was identified as the core category, explaining the central meaning of the respondents' perceptions of the oral health of their elderly patients. The GPs in this study showed little or no awareness of the oral health of their elderly patients. The interviews disclosed several contributing factors. Barriers to closer integration of oral and general health in the elderly were identified. There existed a cultural gap between the disciplines of dentistry and medicine, which does not enhance and may be detrimental to the overall well-being of elderly patients.
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http://dx.doi.org/10.1111/j.1471-6712.2007.00446.xDOI Listing
March 2007