| 1. |
- Albinsson, Sofie, et al.
(författare)
-
Distinct populations of eosinophils in the human thymus with capacity to modulate thymocyte maturation.
- 2023
-
Ingår i: Immunology. - : Wiley. - 0019-2805 .- 1365-2567. ; 169:1, s. 57-68
-
Tidskriftsartikel (refereegranskat)abstract
- Local differentiation of eosinophil precursors occurs in the human thymus. Thymic eosinophils are often positioned in the corticomedullary junction between the CD4+ CD8+ double-positive (DP) thymocytes and the CD4+ or CD8+ single-positive (SP) thymocytes. The aims of this study were to (1) determine if there are distinct thymic eosinophil populations that differ from the blood eosinophil populations and (2) evaluate the capacity of thymic eosinophils to promote the development of SP thymocytes from DP thymocytes. Thymic and blood eosinophils from thymectomized infants (n=7) were compared regarding the expression of 34 molecules using cytometry by time-of-flight (CyTOF). In addition, FACS-sorted thymic eosinophils were co-cultured with autologous CD3/CD28-stimulated DP, CD4 SP, and CD8 SP thymocytes and analysed by flow cytometry and CyTOF. X-shift clustering analysis and viSNE dimensionality reduction were performed. Seven eosinophil populations were identified within the blood and thymus, respectively, five of which were specific for either tissue. Whereas the blood eosinophil populations varied between individuals, the thymic eosinophil populations were more uniform. The eosinophil-thymocyte co-cultures resulted in (1) an increase in CD4 SP thymocytes when eosinophils were cultured with DP thymocytes, (2) decreased frequency of CD8 SP thymocytes when these were cultured with eosinophils, and (3) a more mature thymic phenotype when eosinophils were cultured with CD4 SP thymocytes. Thymic eosinophils are a specialized population of eosinophils with a distinct phenotype that separates them from their blood counterparts, and in vitro they appear to favour CD4 SP thymocyte development to the detriment of CD8 SP thymocytes.
|
|
| 2. |
- Albinsson, Sofie, 1992, et al.
(författare)
-
Eosinophils interact with thymocytes and proliferate in the human thymus
- 2021
-
Ingår i: European journal of immunology. - : Wiley. - 1521-4141 .- 0014-2980. ; 51:6, s. 1539-1541
-
Tidskriftsartikel (refereegranskat)abstract
- Eosinophils differentiate and mature in the thymus, outside of the bone marrow, in healthy individuals. Locally developed thymic eosinophils may contribute to the maturation and selection of human thymocytes.
|
|
| 3. |
- Albinsson, Sofie, 1992, et al.
(författare)
-
Extracellular distribution of galectin-10 in the esophageal mucosa of patients with eosinophilic esophagitis
- 2023
-
Ingår i: CLINICAL AND EXPERIMENTAL IMMUNOLOGY. - : Oxford University Press (OUP). - 0009-9104 .- 1365-2249. ; 212:2, s. 147-155
-
Tidskriftsartikel (refereegranskat)abstract
- CD16+ eosinophils and large amounts of extracellular vesicles containing galectin-10, a T-cell suppressive eosinophil protein, were found in the esophageal mucosa of patients with active eosinophilic esophagitis. Both the CD16+ eosinophils and the released galectin-10-containing extracellular vesicles disappeared in successfully treated patients but remained in the mucosa of the non-responders to treatment. Eosinophilic esophagitis is a T-cell-driven allergic condition hallmarked by eosinophil infiltration of the esophagus. Eosinophils exposed to proliferating T cells release galectin-10 and have T-cell suppressive function in vitro. The aims of this study were to evaluate if eosinophils co-localize with T cells and release galectin-10 in the esophagus of patients with eosinophilic esophagitis. Esophageal biopsies from 20 patients with eosinophilic esophagitis were stained for major basic protein, galectin-10, CD4, CD8, CD16, and CD81 and analyzed by immunofluorescence confocal microscopy before and after topical corticosteroid treatment. CD4+ T-cell numbers decreased in the esophageal mucosa of responders to treatment but not in the non-responders. Suppressive (CD16+) eosinophils were present in the esophageal mucosa of patients with active disease and decreased after successful treatment. Unexpectedly, eosinophils and T cells were not in direct contact with each other. Instead, the esophageal eosinophils released large amounts of galectin-10-containing extracellular vesicles and featured cytoplasmic projections that contained galectin-10, both of which disappeared from the esophagus of the responders but remained in the non-responders. To conclude, the presence of CD16+ eosinophils together with the massive release of galectin-10-containing extracellular vesicles in the esophageal mucosa might indicate that eosinophils exert T-cell suppression in eosinophilic esophagitis.
|
|
| 4. |
- Andersson, Jennie, 1978, et al.
(författare)
-
Eosinophils from hematopoietic stem cell recipients suppress allogeneic T cell proliferation.
- 2014
-
Ingår i: Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. - : Elsevier BV. - 1523-6536. ; 20:12, s. 1891-8
-
Tidskriftsartikel (refereegranskat)abstract
- 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.
|
|
| 5. |
- Ekebergh, Andreas, 1984, et al.
(författare)
-
Exploring a cascade Heck-Suzuki reaction based route to kinase inhibitors using design of experiments
- 2015
-
Ingår i: Organic and biomolecular chemistry. - : Royal Society of Chemistry (RSC). - 1477-0520 .- 1477-0539. ; 13:11, s. 3382-3392
-
Tidskriftsartikel (refereegranskat)abstract
- Design of Experiments (DoE) has been used to optimize a diversity oriented palladium catalyzed cascade Heck-Suzuki reaction for the construction of 3-alkenyl substituted cyclopenta[b]indole compounds. The obtained DoE model revealed a reaction highly dependent on the ligand. Guided by the model, an optimal ligand was chosen that selectively delivered the desired products in high yields. The conditions were applicable with a variety of boronic acids and were used to synthesize a library of 3-alkenyl derivatized compounds. Focusing on inhibition of kinases relevant for combating melanoma, the library was used in an initial structure-activity survey. In line with the observed kinase inhibition, cellular studies revealed one of the more promising derivatives to inhibit cell proliferation via an apoptotic mechanism.
|
|
| 6. |
- Höper, Linnea, et al.
(författare)
-
Vasculitis due to Candidatus Neoehrlichia mikurensis : a cohort study of 40 Swedish patients
- 2021
-
Ingår i: Clinical Infectious Diseases. - : Oxford University Press. - 1058-4838 .- 1537-6591. ; 73:7, s. e2372-e2378
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Candidatus (Ca.) Neoehrlichia (N.) mikurensis is an emerging tick-borne pathogen of humans that is closely related to Ehrlichia and Anaplasma species. This strict intracellular bacterium escapes detection by routine microbiologic diagnostic methods such as blood culture leading to considerable under-diagnosis of the infectious disease it causes, neoehrlichiosis.METHODS: Here, we describe the vascular and thromboembolic events afflicting a series of 40 patients diagnosed with neoehrlichiosis in Sweden during a 10-year period (2009-2019).RESULTS: The majority of the patients (60%) developed vascular events ranging from repeated thrombophlebitis, deep vein thrombosis, pulmonary embolism, transitory ischemic attacks to arteritis. Younger age was a risk factor for vascular complications. In contrast, there was no difference in the incidence of vascular events between immunosuppressed and immunocompetent patients. However, there were qualitative differences such that deep vein thrombosis exclusively afflicted the immunosuppressed patients whereas arteritis was restricted to the immunocompetent ones. We also present the case histories of two patients who developed vasculitis mimicking polyarteritis nodosa and giant cell arteritis. Both were cured by doxycycline treatment.CONCLUSIONS: Ca. N. mikurensis infection should be considered in patients living in tick-endemic areas of Europe and northern Asia who present with atypical vascular and/or thromboembolic events. Early diagnosis and antibiotics targeting this emerging infectious agent can eradicate the infection and prevent the development of new vascular events.
|
|
| 7. |
- Käppi, Timo, 1975, et al.
(författare)
-
Collagenous Gastritis in Children: Incidence, Disease Course, and Associations With Autoimmunity and Inflammatory Markers.
- 2020
-
Ingår i: Clinical and translational gastroenterology. - : Ovid Technologies (Wolters Kluwer Health). - 2155-384X. ; 11:8
-
Tidskriftsartikel (refereegranskat)abstract
- Collagenous gastritis (CG), a rare disorder of unknown etiology, has been postulated to have immune-mediated mechanisms. We investigated (i) the incidence and prevalence of CG in a pediatric population; (ii) the clinical, endoscopic, and histologic characteristics of childhood-onset CG; and (iii) the evidence for autoimmunity and/or inflammatory activity in these patients.Clinical, endoscopic, and histologic data were reviewed longitudinally in a population-based Swedish cohort of 15 patients with childhood-onset CG diagnosed in the period 2008-2019. A set of 11 autoantibodies, 4 blood inflammatory biomarkers, and the human leukocyte antigen DQ2/DQ8 genotype was analyzed cross-sectionally.The incidence rate of childhood-onset CG was 0.25/100,000 person-years, with an incidence rate ratio of girls to boys of 4.2 (95% confidence interval, 1.2-15). The prevalence of CG was 2.1/100,000 in children aged younger than 18 years. The endoscopic and histologic findings remained pathologic in all the examined patients during a median follow-up of 4.4 years. Many patients had heredity for autoimmune disorders (47%) and/or tested positive for autoantibodies (40%) or human leukocyte antigen DQ2/DQ8 (53%). No associated autoimmune comorbidities were observed. The serum levels of calprotectin and amyloid A were increased in 10/15 (67%) and 5/15 (33%) of the patients, respectively, whereas plasma C-reactive protein levels were normal in all, but 1 patient.The results indicate that childhood-onset CG is rare and has a chronic disease course. Although signs of autoimmune predisposition are frequent, early development of autoimmune comorbidities seems seldom. Serum calprotectin and amyloid A represent novel candidate biomarkers of inflammatory activity in CG (see Visual Abstract, Supplementary Digital Content 4, http://links.lww.com/CTG/A349).
|
|
| 8. |
- Käppi, Timo, 1975, et al.
(författare)
-
High frequency of concomitant food allergy development and autoantibody formation in children who have undergone liver transplantation
- 2019
-
Ingår i: Transplantation. - 1534-6080. ; 103:11, s. 2338-2346
-
Tidskriftsartikel (refereegranskat)abstract
- Allergy and other immune-mediated diseases are more frequently reported in children who have undergone liver transplantation. Furthermore, autoantibodies are also prevalent, suggesting a state of immune dysregulation in these patients. Whether or not these processes occur simultaneously in the same individual has not been studied previously.A cohort of 43 children who had undergone liver transplantation for nonautoimmune liver disease at median age of 1.3 years was investigated for allergy and autoimmune disease. Sensitization to food and inhalant allergens was assessed and autoantibodies were measured.The prevalence of food allergy was 26% and that of respiratory allergy was 23%, while 33% and 26% of the subjects were sensitized to food and inhalant allergens, respectively. Autoimmune disease (i.e., autoimmune hepatitis) occurred in a single individual (2%), whereas autoantibodies were present in 44% of the children. Food allergy and autoantibodies occurred concomitantly in 19% of the children, which was almost twice the frequency expected by chance (11%, p=0.04). Respiratory allergy and the presence of autoantibodies were unrelated (12% concurrence vs the expected 10%, p = 0.73). In the logistic regression analysis, autoantibody formation was associated with discontinued immunosuppression and food allergy, with odds ratios of 13 (p=0.01) and 7.1 (p=0.03), respectively.In contrast to respiratory allergy, food allergy and autoantibody formation occurred together in the same children who underwent liver transplantation at a frequency higher than would be expected by chance. This may reflect an underlying immune dysregulation that impairs immune tolerance to both food allergens and autoantigens.
|
|
| 9. |
- Lingblom, Christine, 1984, et al.
(författare)
-
Differences in eosinophil molecular profiles between children and adults with eosinophilic esophagitis.
- 2017
-
Ingår i: Allergy. - : Wiley. - 1398-9995 .- 0105-4538. ; 72:9, s. 1406-1414
-
Tidskriftsartikel (refereegranskat)abstract
- Eosinophilic esophagitis (EoE) afflicts both children and adults. It has been debated whether pediatric and adult EoE represent different disease entities. The objectives of this study were to determine if the blood eosinophil molecular pattern of children with EoE is: 1) distinct from that of healthy children; and 2) different from that of adults with EoE.Blood eosinophils from children and adults with EoE, and healthy controls, were analyzed with flow cytometry regarding levels of CD23, CD44, CD54, CRTH2, FOXP3 and galectin-10. Eosinophil FOXP3 and galectin-10 mRNA levels were determined by qPCR. The data was analyzed by using a multivariate method of pattern recognition.An eosinophil molecular pattern capable of distinguishing children with EoE from control children was identified. A smaller fraction of eosinophils from children with EoE expressed CD44 and a larger fraction expressed CRTH2 than the controls. Eosinophils from children with EoE also had higher levels of galectin-10 mRNA and lower levels of FOXP3 mRNA. The eosinophils from children with EoE had lower levels of surface CD54 and of FOXP3 mRNA compared with the eosinophils from the adult patients. A key finding was the detection in healthy individuals of age-related differences in the levels of several eosinophil markers.Children with EoE can be distinguished from healthy children based on the molecular patterns of their blood eosinophils. Age-related physiologic differences in eosinophil molecular patterns may partly explain the different blood eosinophil phenotypes in children versus adults with EoE. This article is protected by copyright. All rights reserved.
|
|
| 10. |
- Lingblom, Christine, 1984, et al.
(författare)
-
Eosinophils from eosinophilic oesophagitis patients have T cell suppressive capacity and express FOXP3.
- 2017
-
Ingår i: Clinical and Experimental Immunology. - : Oxford University Press (OUP). - 1365-2249 .- 0009-9104. ; 187:3, s. 455-465
-
Tidskriftsartikel (refereegranskat)abstract
- Eosinophilic esophagitis (EoE) is an antigen-driven T cell-mediated chronic inflammatory disease where food and environmental antigens are thought to have a role. Human eosinophils express the immunoregulatory protein galectin-10 and have T cell suppressive capacity similar to regulatory T cells (Tregs ). We hypothesized that one function of eosinophils in EoE might be to regulate the T cell-driven inflammation in the oesophagus. This was tested by evaluating the suppressive capacity of eosinophils isolated from the blood of adult EoE patients in a mixed lymphocyte reaction. In addition, eosinophilic expression of forkhead box protein 3 (FOXP3), the canonical transcription factor of Tregs , was determined by conventional and imaging flow cytometry, quantitative polymerase chain reaction (qPCR), confocal microscopy and immunoblotting. It was found that blood eosinophils from EoE patients had T cell suppressive capacity, and that a fraction of the eosinophils expressed FOXP3. A comparison of EoE eosinophils with healthy control eosinophils indicated that the patients' eosinophils had inferior suppressive capacity. Furthermore, a higher percentage of the EoE eosinophils expressed FOXP3 protein compared with the healthy eosinophils, and they also had higher FOXP3 protein and mRNA levels. FOXP3 was found in the cytosol and nucleus of the eosinophils from both the patients and healthy individuals, contrasting with the strict nuclear localization of FOXP3 in Tregs . To conclude, these findings suggest that the immunoregulatory function of eosinophils may be impaired in EoE.
|
|
| 11. |
- Lingblom, Christine, 1984, et al.
(författare)
-
Kinetic studies of galectin-10 release from eosinophils exposed to proliferating T cells
- 2021
-
Ingår i: Clinical and Experimental Immunology. - : Oxford University Press (OUP). - 0009-9104 .- 1365-2249. ; 203:2, s. 230-234
-
Tidskriftsartikel (refereegranskat)abstract
- Galectin-10 is involved in the T cell suppressive activity of regulatory T cells and eosinophils alike. We have identified a subpopulation of T cell suppressive eosinophils that express CD16 on the surface and contain more galectin-10 compared with conventional CD16-negative eosinophils. Our main goal was to determine how the intracellular protein galectin-10 is released from eosinophils when exposed to proliferating T cells and if such release could be inhibited. Confocal microscopy and imaging flow cytometry were used to study the release of galectin-10 from eosinophils incubated with polyclonally activated T cells. T cell proliferation was monitored by measurement of the incorporation of [H-3]-thymidine. Initially, galectin-10-containing synapses formed between eosinophils and T cells. Subsequently, the plasma membrane of eosinophils began to disintegrate and cap-like accumulations of galectin-10 budded on the eosinophil cell surface. Lastly, eosinophil extracellular traps composed of nuclear DNA and galectin-10 were freed. It was solely the CD16-expressing suppressive eosinophils that formed synapses and eosinophil extracellular traps containing galectin-10. Dissolution of the extracellular traps by DNase I partly abrogated the T cell suppression exerted by eosinophils. Extracellular trap formation has mainly been associated with anti-bacterial defense, but we show a new putative function of these cellular formations, as mediators of T cell suppression by enabling the release of galectin-10 from eosinophils.
|
|
| 12. |
- Lingblom, Christine, 1984, et al.
(författare)
-
Patient-Reported Outcomes and Blood-Based Parameters Identify Response to Treatment in Eosinophilic Esophagitis
- 2021
-
Ingår i: Digestive Diseases and Sciences. - : Springer Science and Business Media LLC. - 0163-2116 .- 1573-2568. ; 66, s. 1556-1564
-
Tidskriftsartikel (refereegranskat)abstract
- Background Noninvasive methods to assess treatment response in eosinophilic esophagitis are needed. Aims Our aim was to determine whether a blood-based biomarker panel centered on immune parameters could identify histologic response to treatment in eosinophilic esophagitis patients. Methods A pilot study involving adult patients with active eosinophilic esophagitis recruited at two Ear, Nose, Throat clinics in Sweden was designed. The patients (n = 20) donated blood and esophageal biopsies and filled in three questionnaires before and after a 2-month course of topical corticosteroids. Blood samples were analyzed for absolute levels of granulocytes and T cells and the fractions of eosinophils expressing 10 different surface markers by flow cytometry. All data were analyzed by multivariate methods of pattern recognition. Results Multivariate modeling revealed that a combination of 13 immune parameters and 10 patient-reported outcome scores were required to create a model capable of separating responders (n = 15) from non-responders (n = 5). Questions regarding symptoms of esophageal dysfunction and capacity to eat certain foods from two of the questionnaires were discriminatory in the multivariate model, as were absolute counts of T cells, eosinophils, and eosinophil expression of activation markers and cell adhesion molecules. Conclusions A combination of blood-based immune parameters and directed questions may prove helpful to monitor response to treatment, perhaps reducing the need for repeat endoscopies in eosinophilic esophagitis patients in the future.
|
|
| 13. |
|
|
| 14. |
- Lingblom, Christine, 1984, et al.
(författare)
-
Regulatory Eosinophils Suppress T Cells Partly through Galectin-10
- 2017
-
Ingår i: Journal of Immunology. - : The American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 198:12, s. 4672-4681
-
Tidskriftsartikel (refereegranskat)abstract
- 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(hi) subset of eosinophils, encompassing 1-5% of all eosinophils, was also identified in the blood of healthy subjects. FACS sorting showed that these CD16(hi) eosinophils were significantly stronger suppressors of T cell proliferation than were conventional CD16 neg 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.
|
|
| 15. |
- Lingblom, Christine, 1984, et al.
(författare)
-
Topical Corticosteroids Do Not Revert the Activated Phenotype of Eosinophils in Eosinophilic Esophagitis but Decrease Surface Levels of CD18 Resulting in Diminished Adherence to ICAM-1, ICAM-2, and Endothelial Cells.
- 2014
-
Ingår i: Inflammation. - : Springer Science and Business Media LLC. - 1573-2576 .- 0360-3997. ; 37:6, s. 1932-1944
-
Tidskriftsartikel (refereegranskat)abstract
- Swallowed topical corticosteroids are the standard therapy for eosinophilic esophagitis (EoE) in adults. Eosinophils in the blood of untreated EoE patients have an activated phenotype. Our aim was to determine if corticosteroids restore the phenotype of eosinophils to a healthy phenotype and if certain cell-surface molecules on blood eosinophils correlate with eosinophilic infiltration of the esophagus. Levels of eight surface markers on eosinophils from treated and untreated EoE patients were determined by flow cytometry and analyzed using multivariate methods of pattern recognition. Corticosteroid-treated EoE patients' eosinophils had decreased levels of CD18 compared to both untreated patients and healthy controls, but maintained their activated phenotype. CD18 expression correlated positively with eosinophil numbers in the esophagus and promoted the adherence of eosinophils to ICAM-1, ICAM-2, and to endothelial cells. The diminished expression of CD18 may be one mechanism behind the reduced entry of eosinophils into the esophagus in corticosteroid-treated EoE patients.
|
|
| 16. |
- Wass, Linda, et al.
(författare)
-
Cultivation of the causative agent of human neoehrlichiosis from clinical isolates identifies vascular endothelium as a target of infection.
- 2019
-
Ingår i: Emerging microbes & infections. - : Informa UK Limited. - 2222-1751. ; 8:1, s. 413-425
-
Tidskriftsartikel (refereegranskat)abstract
- Candidatus (Ca.) Neoehrlichia mikurensis is the cause of neoehrlichiosis, an emerging tick-borne infectious disease characterized by fever and vascular events. The bacterium belongs to the Anaplasmataceae, a family of obligate intracellular pathogens, but has not previously been cultivated, and it is uncertain which cell types it infects. The goals of this study were to cultivate Ca. N. mikurensis in cell lines and to identify possible target cells for human infection. Blood components derived from infected patients were inoculated into cell lines of both tick and human origin. Bacterial growth in the cell cultures was monitored by real-time PCR and imaging flow cytometry. Ca. N. mikurensis was successfully propagated from the blood of immunocompromised neoehrlichiosis patients in two Ixodes spp. tick cell lines following incubation periods of 7-20 weeks. Human primary endothelial cells derived from skin microvasculature as well as pulmonary artery were also susceptible to infection with tick cell-derived bacteria. Finally, Ca. N. mikurensis was visualized within circulating endothelial cells of two neoehrlichiosis patients. To conclude, we report the first successful isolation and propagation of Ca. N. mikurensis from clinical isolates and identify human vascular endothelial cells as a target of infection.
|
|
| 17. |
- Wass, Linda, et al.
(författare)
-
Serological reactivity to Anaplasma phagocytophilum in neoehrlichiosis patients
- 2018
-
Ingår i: European Journal of Clinical Microbiology & Infectious Diseases. - : Springer Science and Business Media LLC. - 0934-9723 .- 1435-4373. ; 37:9, s. 1673-1678
-
Tidskriftsartikel (refereegranskat)abstract
- The tick-borne bacterium Candidatus (Ca.) Neoehrlichia (N.) mikurensis is a cause of "fever of unknown origin" because this strict intracellular pathogen escapes detection by routine blood cultures. Case reports suggest that neoehrlichiosis patients may display serological reactivity to Anaplasma (A.) phagocytophilum. Since Anaplasma serology is part of the diagnostic work-up of undetermined fever in European tick-exposed patients, we wanted to investigate (1) the prevalence of A. phagocytophilum seropositivity among neoehrlichiosis patients, (2) the frequency of misdiagnosed neoehrlichiosis patients among A. phagocytophilum seropositive patients, and (3) the frequency of A. phagocytophilum and Ca. N. mikurensis co-infections. Neoehrlichiosis patients (n = 18) were analyzed for A. phagocytophilum IgM and IgG serum antibodies by indirect immunofluorescence assay. Serum samples from suspected anaplasmosis patients (n = 101) were analyzed for bacterial DNA contents by singleplex PCR specific for A. phagocytophilum and Ca. N. mikurensis, respectively. One fifth of the neoehrlichiosis patients (4/18) were seropositive for IgM and/or IgG to A. phagocytophilum at the time of diagnosis. Among the patients with suspected anaplasmosis, 2% (2/101) were positive for Ca. N. mikurensis by PCR whereas none (0/101) had detectable A. phagocytophilum DNA in the serum. To conclude, patients with suspected anaplasmosis may in fact have neoehrlichiosis. We found no evidence of A. phagocytophilum and Ca. N. mikurensis co-infections in humans with suspected anaplasmosis or confirmed neoehrlichiosis.
|
|
| 18. |
- Albinsson, Sofie, 1992, et al.
(författare)
-
Patient-Reported Dysphagia in Adults with Eosinophilic Esophagitis: Translation and Validation of the Swedish Eosinophilic Esophagitis Activity Index
- 2022
-
Ingår i: Dysphagia. - : Springer Science and Business Media LLC. - 0179-051X .- 1432-0460. ; 37, s. 286-296
-
Tidskriftsartikel (refereegranskat)abstract
- The lack of a Swedish patient-reported outcome instrument for eosinophilic esophagitis (EoE) has limited the assessment of the disease. The aims of the study were to translate and validate the Eosinophilic Esophagitis Activity Index (EEsAI) to Swedish and to assess the symptom severity of patients with EoE compared to a nondysphagia control group. The EEsAI was translated and adapted to a Swedish cultural context (S-EEsAI) based on international guidelines. The S-EEsAI was validated using adult Swedish patients with EoE (n = 97) and an age- and sex-matched nondysphagia control group (n = 97). All participants completed the S-EEsAI, the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Oesophageal Module 18 (EORTC QLQ-OES18), and supplementary questions regarding feasibility and demographics. Reliability and validity of the S-EEsAI were evaluated by Cronbach's alpha and Spearman correlation coefficients between the domains of the S-EEsAI and the EORTC QLQ-OES18. A test-retest analysis of 29 patients was evaluated through intraclass correlation coefficients. The S-EEsAI had sufficient reliability with Cronbach's alpha values of 0.83 and 0.85 for the "visual dysphagia question" and the "avoidance, modification and slow eating score" domains, respectively. The test-retest reliability was sufficient, with good to excellent intraclass correlation coefficients (0.60-0.89). The S-EEsAI domains showed moderate correlation to 6/10 EORTC QLQ-OES18 domains, indicating adequate validity. The patient S-EEsAI results differed significantly from those of the nondysphagia controls (p < 0.001). The S-EEsAI appears to be a valid and reliable instrument for monitoring adult patients with EoE in Sweden.
|
|
| 19. |
- Albinsson, Sofie, 1992, et al.
(författare)
-
Validation of the Swedish Watson Dysphagia Scale for adult patients with eosinophilic esophagitis
- 2022
-
Ingår i: Diseases of the Esophagus. - : Oxford University Press (OUP). - 1120-8694 .- 1442-2050. ; 35:7
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The Swedish Watson Dysphagia Scale (S-WDS) has been used to assess dysphagia in patients with eosinophilic esophagitis (EoE) but has not been validated for this patient group. The aim of this study was to validate the S-WDS for adult patients with EoE. Methods: Ninety-seven Swedish adult patients with EoE and 97 controls without dysphagia filled out the S-WDS, the Swedish Eosinophilic Esophagitis Activity Index (S-EEsAI) and a set of supplementary questions. The reliability of the S-WDS was evaluated using Cronbach's alpha, Pearson correlation of items and total score, and test-retest analysis (n = 29). Validity was investigated using Spearman correlations of the S-WDS items, S-EEsAI domains and a self-assessment score, and by investigating floor and ceiling effects. Results: The Cronbach's alpha of the S-WDS was 0.77 and all items demonstrated moderate to strong correlation to the S-WDS score (r = 0.40-0.81) indicative of sufficient reliability of the instrument. In addition, the test-retest results reflected excellent reliability with an intraclass correlation coefficient of 0.85 for the S-WDS score. Adequate validity of the instrument was demonstrated, the S-WDS score correlated moderately with the self-assessment score and with 4/6 S-EEsAI domains, and strongly with the remaining two domains. Floor effects were more common for liquids and soft-textured foods and ceiling effects increased with increasing food consistency. The S-WDS scores of the patient group were significantly different from those of the nondysphagia control group (P < 0.001). Conclusion: The S-WDS instrument is an appropriate and valid instrument for assessment of dysphagia in patients with EoE.
|
|
| 20. |
|
|
| 21. |
- Beale, M. A., et al.
(författare)
-
Global phylogeny of Treponema pallidum lineages reveals recent expansion and spread of contemporary syphilis
- 2021
-
Ingår i: Nature Microbiology. - : Springer Science and Business Media LLC. - 2058-5276. ; 6:12
-
Tidskriftsartikel (refereegranskat)abstract
- Syphilis, which is caused by the sexually transmitted bacterium Treponema pallidum subsp. pallidum, has an estimated 6.3 million cases worldwide per annum. In the past ten years, the incidence of syphilis has increased by more than 150% in some high-income countries, but the evolution and epidemiology of the epidemic are poorly understood. To characterize the global population structure of T. pallidum, we assembled a geographically and temporally diverse collection of 726 genomes from 626 clinical and 100 laboratory samples collected in 23 countries. We applied phylogenetic analyses and clustering, and found that the global syphilis population comprises just two deeply branching lineages, Nichols and SS14. Both lineages are currently circulating in 12 of the 23 countries sampled. We subdivided T. p.pallidum into 17 distinct sublineages to provide further phylodynamic resolution. Importantly, two Nichols sublineages have expanded clonally across 9 countries contemporaneously with SS14. Moreover, pairwise genome analyses revealed examples of isolates collected within the last 20 years from 14 different countries that had genetically identical core genomes, which might indicate frequent exchange through international transmission. It is striking that most samples collected before 1983 are phylogenetically distinct from more recently isolated sublineages. Using Bayesian temporal analysis, we detected a population bottleneck occurring during the late 1990s, followed by rapid population expansion in the 2000s that was driven by the dominant T. pallidum sublineages circulating today. This expansion may be linked to changing epidemiology, immune evasion or fitness under antimicrobial selection pressure, since many of the contemporary syphilis lineages we have characterized are resistant to macrolides. Global syphilis prevalence has been increasing. Sequencing and analysis of a global collection of 726 Treponema pallidum samples reveal globally circulating lineages linked to a rapid expansion occurring since the end of the twentieth century.
|
|
| 22. |
- Cromvik, Julia, 1980, et al.
(författare)
-
Eosinophils in the blood of hematopoietic stem cell transplanted patients are activated and have different molecular marker profiles in acute and chronic graft-versus-host disease.
- 2014
-
Ingår i: Immunity, inflammation and disease. - : Wiley. - 2050-4527. ; 2:2, s. 99-113
-
Tidskriftsartikel (refereegranskat)abstract
- While increased numbers of eosinophils may be detected in patients with graft-versus-host disease (GVHD) following hematopoietic stem cell transplantation, it is not known if eosinophils play a role in GVHD. The aims of this study were to determine: whether eosinophils are activated during GVHD; whether the patterns of activation are similar in acute and chronic GVHD; and the ways in which systemic corticosteroids affect eosinophils. Transplanted patients (n = 35) were investigated for eosinophil numbers and the expression levels of 16 eosinophilic cell surface markers using flow cytometry; all the eosinophil data were analyzed by the multivariate method OPLS-DA. Different patterns of molecule expression were observed on the eosinophils from patients with acute, chronic, and no GVHD, respectively. The molecules that provided the best discrimination between acute and chronic GVHD were: the activation marker CD9; adhesion molecules CD11c and CD18; chemokine receptor CCR3; and prostaglandin receptor CRTH2. Patients with acute or chronic GVHD who received systemic corticosteroid treatment showed down-regulation of the cell surface markers on their eosinophils, whereas corticosteroid treatment had no effect on the eosinophil phenotype in the patients without GVHD. In summary, eosinophils are activated in GVHD, display different activation profiles in acute and chronic GVHD, and are highly responsive to systemic corticosteroids.
|
|
| 23. |
|
|
| 24. |
- Dadgar, A., et al.
(författare)
-
Fever of unknown origin in a multiple sclerosis patient on immunomodulatory therapy was due to neoehrlichiosis
- 2017
-
Ingår i: Läkartidningen. - 0023-7205. ; 114:38
-
Tidskriftsartikel (refereegranskat)abstract
- The emerging tick-borne bacterium Candidatus Neoehrlichia mikurensis is the etiologic agent of neoehrlichiosis, a febrile illness that may be accompanied by vascular complications. Severe cases of neoehrlichiosis have been described in patients with hematologic malignancies and systemic rheumatic diseases. We present the first case of neoehrlichiosis in a patient with multiple sclerosis undergoing rituximab therapy. © 2017, Swedish Medical Association. All rights reserved.
|
|
| 25. |
- Dieckmann, Regis, et al.
(författare)
-
Antieosinophil Antibodies Alone or in Combination with Antineutrophil Cytoplasmic Antibodies (ANCA) Detected in Different Autoimmune Conditions
- 2023
-
Ingår i: Journal of Immunology Research. - 2314-8861 .- 2314-7156. ; 2023
-
Tidskriftsartikel (refereegranskat)abstract
- Circulating antieosinophil antibodies (AEOSA) have been associated with various autoimmune conditions affecting the liver, kidneys, lungs, and joints but are not part of routine clinical diagnostics. While analyzing human sera for antineutrophil cytoplasmic antibodies (ANCA) by indirect immunofluorescence (IIF) on granulocytes, 0.8% of analyzed samples were found to be reactive with eosinophils. Our aim was to determine the diagnostic relevance and antigenic specificity of AEOSA. AEOSA were seen either in combination with an myeloperoxidase (MPO)-positive p-ANCA (44%; AEOSA+/ANCA+) or on their own (56%; AEOSA+/ANCA-). AEOSA/ANCA positivity was seen in patients with thyroid disease (44%) or vasculitis (31%), while AEOSA+/ANCA- pattern was more common in patients with autoimmune disorders of the gastrointestinal tract and/or liver. Eosinophil peroxidase (EPX) was the main target recognized in 66% of the AEOSA+ sera by enzyme-linked immunosorbent assay (ELISA). Eosinophil cationic protein (ECP) and eosinophil-derived neurotoxin (EDN) were also identified as target antigens but less frequently and only in combination with EPX. In conclusion, we confirmed that EPX is a major target of AEOSA, illustrating the high antigenic potential of EPX. Our results also demonstrate the presence of concomitant AEOSA/ANCA positivity in a defined patient group. Further research should aim to elucidate the association of AEOSA with autoimmunity.
|
|
| 26. |
- Eimer, Johannes, et al.
(författare)
-
Spiroplasma ixodetis Infections in Immunocompetent and Immunosuppressed Patients after Tick Exposure, Sweden
- 2022
-
Ingår i: Emerging Infectious Diseases. - : Centers for Disease Control and Prevention (CDC). - 1080-6040 .- 1080-6059. ; 28:8, s. 1681-1685
-
Tidskriftsartikel (refereegranskat)abstract
- We report 2 cases of Spiroplasma ixodetis infection in an immunocompetent patient and an immunocompromised patient who had frequent tick exposure. Fever, thrombocytopenia, and increased liver aminotransferase levels raised the suspicion of anaplasmosis, but 16S rRNA PCR and Sanger sequencing yielded a diagnosis of spiroplasmosis. Both patients recovered after doxycycline treatment.
|
|
| 27. |
|
|
| 28. |
- Grankvist, A., et al.
(författare)
-
Comparative Genomics of Clinical Isolates of the Emerging Tick-Borne Pathogen Neoehrlichia mikurensis
- 2021
-
Ingår i: Microorganisms. - : MDPI AG. - 2076-2607. ; 9:7
-
Tidskriftsartikel (refereegranskat)abstract
- Tick-borne 'Neoehrlichia (N.) mikurensis' is the cause of neoehrlichiosis, an infectious vasculitis of humans. This strict intracellular pathogen is a member of the family Anaplasmataceae and has been unculturable until recently. The only available genetic data on this new pathogen are six partially sequenced housekeeping genes. The aim of this study was to advance the knowledge regarding 'N. mikurensis' genomic relatedness with other Anaplasmataceae members, intra-species genotypic variability and potential virulence factors explaining its tropism for vascular endothelium. Here, we present the de novo whole-genome sequences of three 'N. mikurensis' strains derived from Swedish patients diagnosed with neoehrlichiosis. The genomes were obtained by extraction of DNA from patient plasma, library preparation using 10x Chromium technology, and sequencing by Illumina Hiseq-4500. 'N. mikurensis' was found to have the next smallest genome of the Anaplasmataceae family (1.1 Mbp with 27% GC contents) consisting of 845 protein-coding genes, every third of which with unknown function. Comparative genomic analyses revealed that 'N. mikurensis' was more closely related to Ehrlichia chaffeensis than to Ehrlichia ruminantium, the opposite of what 16SrRNA sequence-based phylogenetic analyses determined. The genetic variability of the three whole-genome-sequenced 'N. mikurensis' strains was extremely low, between 0.14 and 0.22 parts per thousand, a variation that was associated with geographic origin. No protein-coding genes exclusively shared by N. mikurensis and E. ruminantium were identified to explain their common tropism for vascular endothelium.
|
|
| 29. |
- Grankvist, Anna, et al.
(författare)
-
Infections with Candidatus Neoehrlichia mikurensis and Cytokine Responses in 2 Persons Bitten by Ticks, Sweden
- 2015
-
Ingår i: Emerging Infectious Diseases. - : Centers for Disease Control and Prevention (CDC). - 1080-6040 .- 1080-6059. ; 21:8, s. 1462-1465
-
Tidskriftsartikel (refereegranskat)abstract
- The prevalence of Candidatus Neoehrlichia mikurensis infection was determined in 102 persons bitten by ticks in Sweden. Two infected women had erythematous rashes; 1 was co-infected with a Borrelia sp., and the other showed seroconversion for Anaplasma phagocytophilum. Both patients had increased levels of Neoehrlichia DNA and serum cytokines for several months.
|
|
| 30. |
- Grankvist, Anna, et al.
(författare)
-
Infections With the Tick-Borne Bacterium "Candidatus Neoehrlichia mikurensis" Mimic Noninfectious Conditions in Patients With B Cell Malignancies or Autoimmune Diseases
- 2014
-
Ingår i: Clinical Infectious Diseases. - : Oxford University Press (OUP). - 1058-4838 .- 1537-6591. ; 58:12, s. 1716-1722
-
Tidskriftsartikel (refereegranskat)abstract
- Background. Candidatus Neoehrlichia mikurensis is a newly discovered noncultivatable bacterium spread among ticks and rodents in Europe and Asia that can infect humans, particularly immunocompromised patients. Methods.aEuro integral We compiled clinical and laboratory data from 11 patients with hematological malignances or autoimmune diseases who were diagnosed with Candidatus N. mikurensis infection in Europe 2010-2013. Both published (6) and unpublished cases (5) were included. Results.aEuro integral The patients had a median age of 67, were mostly male (8/11), and resided in Sweden, Switzerland, Germany, and the Czech Republic. All but one had ongoing or recent immune suppressive treatment and a majority were splenectomized (8/11). Less than half of them recalled tick exposure. The most frequent symptoms were fever (11/11), localized pain afflicting muscles and/or joints (8/11), vascular and thromboembolic events (6/11), that is, deep vein thrombosis (4), transitory ischemic attacks (2), pulmonary embolism (1), and arterial aneurysm (1). Typical laboratory findings were elevated C-reactive protein, leukocytosis with neutrophilia, and anemia. Median time from onset of symptoms to correct diagnosis was 2 months. In at least 4 cases, the condition was interpreted to be due to the underlying disease, and immunosuppressive therapy was scheduled. All patients recovered completely when doxycycline was administered. Conclusions.aEuro integral Candidatus N. mikurensis is an emerging tick-borne pathogen that may give rise to a systemic inflammatory syndrome in persons with hematologic or autoimmune diseases that could be mistaken for recurrence of the underlying disease and/or unrelated arteriosclerotic vascular events. Awareness of this new pathogen is warranted among rheumatologists, hematologists, oncologists, and infectious disease specialists.
|
|
| 31. |
- Grankvist, Anna, et al.
(författare)
-
Multilocus sequence analysis of clinical "candidatus neoehrlichia mikurensis" strains from Europe
- 2015
-
Ingår i: Journal of Clinical Microbiology. - 0095-1137 .- 1098-660X. ; 53:10, s. 3126-3132
-
Tidskriftsartikel (refereegranskat)abstract
- Copyright © 2015, American Society for Microbiology. All Rights Reserved. Candidatus Neoehrlichia mikurensis" is the tick-borne agent of neoehrlichiosis, an infectious disease that primarily affects immunocompromised patients. So far, the genetic variability of "Ca. Neoehrlichia" has been studied only by comparing 16S rRNA genes and groEL operon sequences. We describe the development and use of a multilocus sequence analysis (MLSA) protocol to characterize the genetic diversity of clinical "Ca. Neoehrlichia" strains in Europe and their relatedness to other species within the Anaplasmataceae family. Six genes were selected: ftsZ, clpB, gatB, lipA, groEL, and 16S rRNA. Each MLSA locus was amplified by real-time PCR, and the PCR products were sequenced. Phylogenetic trees of MLSA locus relatedness were constructed from aligned sequences. Blood samples from 12 patients with confirmed "Ca. Neoehrlichia" infection from Sweden (n9), the Czech Republic (n2), and Germany (n1) were analyzed with the MLSA protocol. Three of the Swedish strains exhibited identical lipA sequences, while the lipA sequences of the strains from the other nine patients were identical to each other. One of the Czech strains had one differing nucleotide in the clpB sequence from the sequences of the other 11 strains. All 12 strains had identical sequences for the genes 16S rRNA, ftsZ, gatB, and groEL. According to the MLSA, among the Anaplasmataceae, "Ca. Neoehrlichia" is most closely related to Ehrlichia ruminantium, less so to Anaplasma phagocytophilum, and least to Wolbachia endosymbionts. To conclude, three sequence types of infectious "Ca. Neoehrlichia" were identified: one in the west of Sweden, one in the Czech Republic, and one spread throughout Europe.
|
|
| 32. |
- Hammarström, Helena, et al.
(författare)
-
Fungal Tracheobronchitis in Lung Transplant Recipients : Incidence and Utility of Diagnostic Markers
- 2023
-
Ingår i: Journal of Fungi. - : MDPI AG. - 2309-608X. ; 9:1
-
Tidskriftsartikel (refereegranskat)abstract
- Fungal tracheobronchitis caused by Aspergillus and Candida spp. is a recognized complication after lung transplantation, but knowledge of the incidence of Candida tracheobronchitis is lacking. The diagnosis relies on fungal cultures in bronchoalveolar lavage fluid (BALF), but cultures have low specificity. We aimed to evaluate the one-year incidence of fungal tracheobronchitis after lung transplantation and to assess the utility of diagnostic markers in serum and BALF to discriminate fungal tracheobronchitis from colonization. Ninety-seven consecutively included adult lung-transplant recipients were prospectively followed. BALF and serum samples were collected at 1, 3 and 12 months after transplantation and analyzed for betaglucan (serum and BALF), neutrophils (BALF) and galactomannan (BALF). Fungal tracheobronchitis was defined according to consensus criteria, modified to include Candida as a mycologic criterion. The cumulative one-year incidence of Candida and Aspergillus tracheobronchitis was 23% and 16%, respectively. Neutrophils of >75% of total leukocytes in BALF had 92% specificity for Candida tracheobronchitis. The area under the ROC curves for betaglucan and galactomannan in BALF to discriminate Aspergillus tracheobronchitis from colonization or no fungal infection were high (0.86 (p < 0.0001) and 0.93 (p < 0.0001), respectively). To conclude, the one-year incidence of fungal tracheobronchitis after lung transplantation was high and dominated by Candida spp. Diagnostic markers in BALF could be useful to discriminate fungal colonization from tracheobronchitis.
|
|
| 33. |
- Hammarström, Helena, et al.
(författare)
-
How to interpret serum levels of beta-glucan for the diagnosis of invasive fungal infections in adult high-risk hematology patients: optimal cut-off levels and confounding factors
- 2015
-
Ingår i: European Journal of Clinical Microbiology and Infectious Diseases. - : Springer Science and Business Media LLC. - 0934-9723 .- 1435-4373. ; 34:5, s. 917-925
-
Tidskriftsartikel (refereegranskat)abstract
- Detection of the fungal cell wall component beta-glucan (BG) in serum is increasingly used to diagnose invasive fungal infections (IFI), but its optimal use in hematology patients with high risk of IFI is not well defined. We retrospectively analyzed the diagnostic accuracy, optimal cut-off level, and potential confounding factors of BG reactivity. The inclusion criteria were: adult patients with hematologic disease who were admitted to the hematology ward during the 2-year study period and who had two or more consecutive BG assays performed. In total, 127 patients were enrolled. Thirteen patients with proven or probable IFI, as defined by the 2008 European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) criteria, were identified. Receiver operating characteristic (ROC) curve analysis showed a high overall diagnostic performance (area under the ROC curve = 0.98) and suggested an optimal cut-off level of 158pg/ml, with a sensitivity and a specificity of 92% and 96%, respectively. Multiway analysis of variance indicated that treatment with pegylated asparaginase (p < 0.001), admission to the intensive care unit (ICU; p = 0.0007), and treatment with albumin, plasma, or coagulation factors (p = 0.01) are potential confounding factors of BG reactivity. We propose that a higher cut-off level than that recommended by the manufacturer should be used to monitor adult hematology patients at high risk for IFI. Our results also suggest that elevated BG levels in patients treated with pegylated asparaginase, albumin, plasma, or coagulation factors, or those admitted to the ICU should be interpreted with caution. © 2015, Springer-Verlag Berlin Heidelberg.
|
|
| 34. |
- Hammarström, Helena, et al.
(författare)
-
Prospective evaluation of a combination of fungal biomarkers for the diagnosis of invasive fungal disease in high-risk haematology patients
- 2018
-
Ingår i: Mycoses. - : Wiley. - 0933-7407 .- 1439-0507. ; 61:9, s. 623-632
-
Tidskriftsartikel (refereegranskat)abstract
- We prospectively evaluated a combination of fungal biomarkers in adult haematology patients with focus on their clinical utility at different time points during the course of infection. In total, 135 patients were monitored once to twice weekly for serum (1-3)-ß-d-glucan (BG), galactomannan (GM), bis-methyl-gliotoxin and urinary d-arabinitol/l-arabinitol ratio. In all, 13 cases with proven or probable invasive fungal disease (IFD) were identified. The sensitivity of BG and GM at the time of diagnosis (TOD) was low, but within 2 weeks from the TOD the sensitivity of BG was 92%. BG >800 pg/mL was highly specific for IFD. At a pre-test probability of 12%, both BG and GM had negative predictive values (NPV) >0.9 but low positive predictive values (PPV). In a subgroup analysis of patients with clinically suspected IFD (pre-test probability of 35%), the NPV was lower, but the PPV for BG was 0.86 at cut-off 160 pg/mL. Among IFD patients, 91% had patterns of consecutively positive and increasing BG levels. Bis-methyl-gliotoxin was undetectable in 15 patients with proven, probable and possible IA. To conclude, BG was the superior fungal marker for IFD diagnosis. Quantification above the limit of detection and graphical evaluation of the pattern of dynamics are warranted in the interpretation of BG results.
|
|
| 35. |
- Hammarström, Helena, et al.
(författare)
-
Serum-based diagnosis of Pneumocystis pneumonia by detection of Pneumocystis jirovecii DNA and 1,3-beta-D-glucan in HIV-infected patients: a retrospective case control study
- 2019
-
Ingår i: BMC Infectious Diseases. - : Springer Science and Business Media LLC. - 1471-2334. ; 19
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundPneumocystis jirovecii pneumonia (PCP) is one of the most common HIV-related opportunistic infections. The diagnosis of PCP is based on analyses from respiratory tract specimens which may require the invasive procedure of a diagnostic bronchoscopy. The objective of this study was to evaluate the diagnostic potential of Pneumocystis jirovecii PCR in serum combined with the 1,3-beta-D-glucan (betaglucan) test for the diagnosis of PCP in HIV-infected patients.MethodsThis was a retrospective case-control study including serum samples from 26 HIV-infected patients with PCP collected within 5days prior to the start of PCP treatment, 21 HIV-infected control subjects matched by blood CD4(+) cell counts, and 18 blood donors. The serum samples were analyzed for Pneumocystis jirovecii PCR and betaglucan. The reference standard for PCP was based on previously described microbiological and clinical criteria.ResultsAll patients with PCP had detectabe Pneumocystis jirovecii DNA in serum yielding a sensitivity for the Pneumocystis jirovecii PCR assay in serum of 100%. All blood donors had negative Pneumocystis PCR in serum. The specificity when testing HIV-infected patients was 71%, but with a PCR Cycle threshold (Ct) value of 34 as cut-off the specificity was 90%. At a putative pretest probaility of 20%, the negative and positive predictive value for the Pneumocystis PCR assay in serum was 0.99 and 0.71, respectively. Betaglucan with cut-off level 200pg/ml combined with a positive Pneumocystis jirovecii PCR result had sensitivity and specificity of 92 and 90%, respectively. The concentration of Pneumocystis jirovecii DNA in serum samples, expressed by the PCR Ct values, correlated inversely to the betaglucan levels in serum.ConclusionIn this case-control study including 70% of all HIV-infected patients with PCP treated at Sahlgrenska University Hospital during a time period of 13years, Pneumocystis PCR analysis on serum samples had a very high sensitivity and negative predictive value for the diagnosis of PCP in HIV-infected patients. A serum-based diagnostic procedure either based on Pneumocystis jirovecii PCR alone or in combination with betaglucan analysis may thus be feasible and would facilitate the care of HIV-infected patients with suspected PCP.
|
|
| 36. |
- Johansson, Sofi, 1975, et al.
(författare)
-
CC16 Inhibits the Migration of Eosinophils Towards the Formyl Peptide fMLF but not Towards PGD(2).
- 2009
-
Ingår i: Inflammation. - : Springer Science and Business Media LLC. - 0360-3997 .- 1573-2576. ; 32:2, s. 65-9
-
Tidskriftsartikel (refereegranskat)abstract
- 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.
|
|
| 37. |
|
|
| 38. |
- Karlsson, Johanna, 1973, et al.
(författare)
-
Comparative Study of Immune Status to Infectious Agents in Elderly Patients with Multiple Myeloma, Waldenstrom's Macroglobulinemia, and Monoclonal Gammopathy of Undetermined Significance.
- 2011
-
Ingår i: Clinical and vaccine immunology : CVI. - 1556-6811. ; 18:6, s. 969-77
-
Tidskriftsartikel (refereegranskat)abstract
- Whereas patients with multiple myeloma (MM) have a well-documented susceptibility to infections, this has been less studied in other B-cell disorders, such as Waldenstrom's macroglobulinemia (WM) and monoclonal gammopathy of undetermined significance (MGUS). We investigated the humoral immunity to 24 different pathogens in elderly patients with MM (n = 25), WM (n = 16), and MGUS (n = 18) and in age-matched controls (n = 20). Antibody titers against pneumococci, staphylococcal alpha-toxin, tetanus and diphtheria toxoids, and varicella, mumps, and rubella viruses were most depressed in MM patients, next to lowest in WM and MGUS patients, and highest in the controls. In contrast, levels of antibodies specific for staphylococcal teichoic acid, Moraxella catarrhalis, candida, aspergillus, and measles virus were similarly decreased in MM and MGUS patients. Comparable titers in all study groups were seen against Haemophilus influenzae type b (Hib), borrelia, toxoplasma, and members of the herpesvirus family. Finally, a uniform lack of antibodies was noted against Streptococcus pyogenes, salmonella, yersinia, brucella, francisella, and herpes simplex virus type 2. To conclude, although MM patients displayed the most depressed humoral immunity, significantly decreased antibody levels were also evident in patients with WM and MGUS, particularly against Staphylococcus aureus, pneumococci, and varicella. Conversely, immunity was retained for Hib and certain herpesviruses in all study groups.
|
|
| 39. |
- Karlsson, Johanna, 1973, et al.
(författare)
-
Pneumococcal vaccine responses in elderly patients with multiple myeloma, Waldenstrom’s macroglobulinemia, and monoclonal gammopathy of undetermined significance
- 2013
-
Ingår i: Trials in vaccinology. - : Elsevier BV. - 1879-4378. ; 2, s. 31-38
-
Tidskriftsartikel (refereegranskat)abstract
- Background Vaccination with the 23-valent pneumococcal polysaccharide vaccine (PPV) has been recommended for elderly patients with B cell malignancies and dysfunctions because of their enhanced susceptibility to pneumococcal infections. More recent recommendations advocate the use of conjugate pneumococcal vaccines. Methods We compared responses to single dose vaccination with either PPV or the 7-valent pneumococcal conjugate vaccine (PCV7) in fifty-six patients ⩾60 years with a diagnosis of multiple myeloma (n = 24), Waldenstrom’s macroglobulinemia (n = 15) and the non-malignant B cell disorder monoclonal gammopathy of undetermined significance (MGUS) (n = 17), and 20 age-matched controls. Serum was collected prior to vaccination and 4–8 weeks later, and analyzed for IgG antibody levels to pneumococcal serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F by ELISA. Functional antibody activity towards pneumococcal serotypes 4 and 14 was measured using an opsonophagocytic killing assay (OPA). Results All patient groups had lower pre-vaccination IgG antibody and OPA titers to the investigated serotypes compared to the healthy controls. Following vaccination, myeloma patients responded with significant IgG titer increases to 1/7 serotypes and OPA titer increases to 1/2 serotypes. Corresponding IgG and OPA vaccine responses were 3/7 and 0/2 for Waldenstrom patients, 4/7 and 1/2 for MGUS patients, and 4/7 and 2/2 for the healthy controls, respectively. Notably high antibody levels without corresponding OPA titers were seen among a few myeloma patients indicating the presence of non-functional antibodies. Neither of the two vaccines elicited significantly higher serotype-specific IgG concentrations, OPA titers or antibody fold increases in any of the study groups. Hypogammaglobulinemia and ongoing chemotherapy were associated with poor vaccine responses in a multivariate analysis. Conclusion Our findings confirm that B cell malignancies and disorders among elderly patients are associated with suboptimal responses to pneumococcal vaccination. Single-dose PCV7 was not shown to be superior to PPV.
|
|
| 40. |
- Karlsson, Johanna, 1973, et al.
(författare)
-
Poor correlation between pneumococcal IgG and IgM titers and opsonophagocytic activity in vaccinated patients with multiple myeloma and Waldenstrom's macroglobulinemia
- 2016
-
Ingår i: Clinical and Vaccine Immunology. - 1556-6811 .- 1556-679X. ; 23:4, s. 379-385
-
Tidskriftsartikel (refereegranskat)abstract
- Patients with multiple myeloma and other B cell disorders respond poorly to pneumococcal vaccination. Vaccine responsiveness is commonly determined by measuring pneumococcal serotype-specific antibodies by enzyme-linked immunosorbent assay (ELISA), by a functional opsonophagocytosis assay (OPA), or by both assays. We compared the two methods in vaccinated elderly patients with multiple myeloma, Waldenstrom’s macroglobulinemia, and monoclonal gammopathy of undetermined significance (MGUS). Postvaccination sera from 45 patients (n=15 from each patient group) and 15 control subjects were analyzed by multiplexed OPA for pneumococcal serotypes 4, 6B, 14, and 23F, and the results were compared to IgG and IgM antibody titers measured by ELISA. While there were significant correlations between pneumococcal OPA and IgG titers for all serotypes among the control subjects (correlation coefficients [r] between 0.51 and 0.85), no significant correlations were seen for any of the investigated serotypes in the myeloma group (r.018 to 0.21) or in the group with Waldenstrom’s macroglobulinemia (borderline significant correlations for 2 of 4 serotypes). The MGUS group resembled the control group by having good agreement between the two test methods for 3 of 4 serotypes (r0.53 to 0.80). Pneumococcal postvaccination IgM titers were very low in the myeloma patients compared to the other groups and did not correlate with the OPA results. To summarize, our data indicate that ELISA measurements may overestimate antipneumococcal immunity in elderly subjects with B cell malignancies and that a functional antibody test should be used specifically for myeloma and Waldenstrom’s macroglobulinemia patients.
|
|
| 41. |
- Kondori, Nahid, 1967, et al.
(författare)
-
Comparison of a new commercial test, Dermatophyte-PCR kit, with conventional methods for rapid detection and identification of Trichophyton rubrum in nail specimens.
- 2010
-
Ingår i: Medical mycology : official publication of the International Society for Human and Animal Mycology. - : Oxford University Press (OUP). - 1460-2709. ; 48:7, s. 1005-8
-
Tidskriftsartikel (refereegranskat)abstract
- The performance of a new commercially available duplex PCR, which combines pan-dermatophyte PCR with a Trichophyton rubrum-specific PCR, was evaluated. This Dermatophyte PCR kit, which requires one day for laboratory diagnosis, was compared with the conventional methods of microscopy and culture that necessitate up to 4 weeks for final diagnosis of dermatophytosis. We studied 177 nail samples from patients with suspected onychomycosis by fluorescence microscopy (blankophore), cultures and the Dermatophyte PCR kit. More samples were positive by PCR (78/177, 44%) than by culture (59/177, 34%). T. rubrum was present in 95% of all culture-positive nail specimens, which was confirmed by PCR in 55/56 specimens. The positive predictive value, negative predictive value, specificity and sensitivity of the duplex PCR was 93%, 87%, 94% and 85%, respectively, when confirmed by positive culture, microscopy or both. Due to its sensitivity, specificity and rapidity, we conclude that this PCR is an attractive method for routine investigation of nail dermatophytosis in a clinical setting.
|
|
| 42. |
- Kondori, Nahid, 1967, et al.
(författare)
-
Development of IgG antibodies to Exophiala dermatitidis is associated with inflammatory responses in patients with cystic fibrosis.
- 2014
-
Ingår i: Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society. - : Elsevier BV. - 1873-5010. ; 13:4, s. 391-399
-
Tidskriftsartikel (refereegranskat)abstract
- The clinical importance of airway colonisation by the fungus Exophiala dermatitidis in patients with cystic fibrosis (CF) is unclear. We have previously shown that E. dermatitidis frequently colonises the airways of patients with CF. The aims of the present study were to determine whether patients who are colonised by E. dermatitidis have detectable fungal antigens in the circulation, develop anti-fungal antibodies, and show signs of inflammation and impaired respiratory function.
|
|
| 43. |
- Kondori, Nahid, 1967, et al.
(författare)
-
High recovery rate of Exophiala dermatitidis in the airways of cystic fibrosis patients is associated with pancreatic insufficiency.
- 2011
-
Ingår i: Journal of clinical microbiology. - 1098-660X. ; Mar (49):3, s. 1004-9
-
Tidskriftsartikel (refereegranskat)abstract
- The black pigmented fungus, Exophiala dermatitidis is considered to be a harmless colonizer of the airways of cystic fibrosis (CF) patients. The aim of this study was to establish the recovery rate of E. dermatitidis in respiratory specimens of CF patients, transplant recipients and subjects with other respiratory disorders in Sweden. Secondly, we wished to determine if particular clinical traits were associated with E. dermatitidis colonization of the airways, and the antifungal susceptibility profiles of Exophiala strains. Sputum and bronchoalveolar lavage samples (n=492) derived from 275 patients were investigated. E. dermatitidis was isolated in respiratory specimens of 19% (18/97) of the CF patients but in none of the other patient categories. All isolates were recovered after 6-25 days of incubation on erythritol-chloramphenicol (ECA) medium. Morphological and genetic analyses confirmed species identity. Pancreatic insufficiency was positively associated with the presence of E. dermatitidis in sputum samples (P= 0.0198). Antifungal susceptibility tests demonstrated that voriconazole and posaconazole had the lowest MICs against E. dermatitidis. To conclude, E. dermatitidis is a frequent colonizer of the respiratory tract of CF patients in Sweden, and appears to be associated with more advanced disease. Whether E. dermatitidis is pathogenic or not remains to be elucidated.
|
|
| 44. |
|
|
| 45. |
- Mohammad, Ghayeb, et al.
(författare)
-
Isolated eosinophilic myometritis: A case report of an extremely rare phenomenon
- 2021
-
Ingår i: International Journal of Gynecological Pathology. - 0277-1691 .- 1538-7151. ; 41:3
-
Tidskriftsartikel (refereegranskat)abstract
- Increased number of eosinophils in the uterus has been reported under physiological and pathologic conditions. However, eosinophilic infiltration limited to the myometrium is very unusual. A rare finding of isolated eosinophilic infiltration in the myometrium without involvement of endometrium or pathologies in the cervix or ovaries was observed in a 31-yr-old woman seeking medical attention for unexplained infertility, abnormal uterine bleeding, and dysmenorrhea. The patient had no allergies, parasitic disease, or other systemic disorders. This rare manifestation of eosinophilic infiltration expands the differential diagnosis of inflammatory conditions of the myometrium in patients with gynecological issues.
|
|
| 46. |
- Quarsten, H., et al.
(författare)
-
Candidatus Neoehrlichia mikurensis and Borrelia burgdorferi sensu lato detected in the blood of Norwegian patients with erythema migrans
- 2017
-
Ingår i: Ticks and Tick-Borne Diseases. - : Elsevier BV. - 1877-959X. ; 8:5, s. 715-720
-
Tidskriftsartikel (refereegranskat)abstract
- The most common tick-borne human disease in Norway is Lyme borreliosis. Ticks in Norway also harbour less known disease-causing agents such as Candidatus Neoehrlichia mikurensis, Borrelia miyamotoi and Rickettsia heivetica. However, human infections caused by these pathogens have never been described in Norway. The main aims of the study were to evaluate the contribution of several tick-borne bacterial agents, other than Borrelia burgdorferi sensu lato, to zoonotic diseases in Norway and to determine their clinical pictures. Blood samples from 70 symptomatic tick-bitten adults from the Agder counties in southern Norway were screened for seven tick-borne pathogens by using a commercial multiplex PCR-based method and by singleplex real-time PCR protocols. Most patients (65/70) presented with a rash clinically diagnosed as erythema migrans (EM). The most frequently detected pathogen DNA was from Ca. N. mikurensis and was found in the blood of 10% (7/70) of the patients. The Ca. N. mikurensis-infected patients presented with an EM-like rash as the only symptom. B. burgdorferi s.l. DNA was present in the blood of 4% (3/70) of the study participants. None had detectable Anaplasma phagocytophilum, B. miyamotoi, Rickettsia typhus group or spotted fever group, Francisella tularensis, Coxiella burnetii or Battonella spp. DNA in the blood. The commercially available multiplex PCR bacteria flow chip system failed to identify half of the infected patients detected by corresponding real-time PCR protocols. The recovery of Ca. N. mikurensis DNA was higher in the pellet/plasma fraction of blood than from whole blood. To conclude, Co.. N. mikurensis appeared to be the etiological agent in patients with EM in a surprisingly large fraction of tick-bitten persons in the southern part of Norway.
|
|
| 47. |
- Quarsten, H., et al.
(författare)
-
Tick-borne Pathogens Detected in the Blood of Immunosuppressed Norwegian Patients Living in a Tick-endemic Area
- 2021
-
Ingår i: Clinical Infectious Diseases. - : Oxford University Press (OUP). - 1058-4838 .- 1537-6591. ; 73:7
-
Tidskriftsartikel (refereegranskat)abstract
- Background. The knowledge regarding the occurrence and the clinical implications of tick-borne infections in immunosuppressed patients living in tick-endemic areas is limited. Methods. Adult patients with autoimmune conditions requiring immunosuppressive treatment such as infliximab and rituximab were invited to participate in the study when they attended the hospital for treatment and/or control of the disease. Whole-blood samples were analyzed by real-time polymerase chain reaction for Borrelia burgdorferi sensu lato, Borrelia miyamotoi, Anaplasma phagocytophilum, Rickettsia spp., Candidatus Neoehrlichia mikurensis, and Babesia spp. Results. The occurrence of tick-borne pathogens in the blood of patients (n = 163) with autoimmune conditions requiring immunosuppressive treatment was evaluated. Pathogen DNA was detected in 8.6% (14/163) of the patients. The predominant pathogen was Ca. Neoehrlichia mikurensis (12/14), which was carried in the blood of infected patients for 10-59 days until treatment with doxycycline. B. burgdorferi s.l. and Rickettsia spp. were detected in 1 patient each. The B. burgdorferi-infected patient presented with fever, whereas the remaining patients were judged to have subclinical infections. B. miyamotoi, A. phagocytophilum, and Babesia spp. were not detected in any patient. Conclusions. Patients treated with biologicals and living in a tick-endemic area seem to have a high risk of contracting Ca. Neoehrlichia mikurensis infection, which, if left untreated, could result in thromboembolic complications.
|
|
| 48. |
|
|
| 49. |
- Sjöwall, Johanna, et al.
(författare)
-
Neoehrlichia mikurensis & nbsp;Causing Thrombosis and Relapsing Fever in a Lymphoma Patient Receiving Rituximab
- 2021
-
Ingår i: Microorganisms. - : MDPI AG. - 2076-2607. ; 9:10
-
Tidskriftsartikel (refereegranskat)abstract
- Neoehrlichia (N.) mikurensis, an intracellular tick-borne bacterium not detected by routine blood culture, is prevalent in ticks in Scandinavia, Central Europe and Northern Asia, and may cause long-standing fever, nightly sweats, migrating pain, skin rashes and thromboembolism, especially in patients treated with rituximab. The multiple symptoms may raise suspicion of both infection, inflammation and malignancy, and lead in most cases to extensive medical investigations across many medical specialist areas and a delay of diagnosis. We describe a complex, albeit typical, case of neoehrlichiosis in a middle-aged splenectomised male patient with a malignant lymphoma, receiving treatment with rituximab. The multifaceted clinical picture associated with this tick-borne disease is addressed, and longitudinal clinical and laboratory data, as well as imaging, are provided. Longstanding relapsing fever in combination with thrombosis in superficial and deep veins in an immunocompromised patient living in a tick-endemic region should raise the suspicion of the emerging tick-borne disease neoehrlichiosis. Given the varied clinical presentation and the risk of delay in diagnosis and treatment, we believe it is important to raise clinicians' awareness of this emerging infection, which is successfully treated with doxycycline.
|
|
| 50. |
- Skovbjerg, Susann, 1973, et al.
(författare)
-
Optimization of the detection of microbes in blood from immunocompromised patients with haematological malignancies.
- 2009
-
Ingår i: Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases. - : Elsevier BV. - 1469-0691. ; 15:7, s. 680-3
-
Tidskriftsartikel (refereegranskat)abstract
- The present study aimed to improve the rate of detection of blood-borne microbes by using PCRs with pan-bacterial and Candida specificity. Seventeen per cent of the blood samples (n=178) collected from 107 febrile patients with haematological malignancies were positive using standard culture (BacT/Alert system). Candida PCR was positive in 12 patients, only one of whom scored culture-positive. Bacterial PCR using fresh blood samples was often negative, but the detection rate increased when the blood was pre-incubated for 2 days. These data indicate that PCR assays might be a complement for the detection of blood-borne opportunists in immunocompromised haematology patients.
|
|
