J Lundahl

Karolinska University Hospital, Tukholma, Stockholm, Sweden

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Publications (171)579.82 Total impact

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    ABSTRACT: The hemodialysis procedure involves contact between peripheral blood and the surface of dialyzer membranes, which may lead to alterations in the pathways of innate and adaptive immunity. We aimed to study the effect of blood–membrane interaction on human peripheral basophils and neutrophils in hemodialysis with high- and low-permeability polysulfone dialyzers. The surface expression of CD203c (basophil selection marker) and CD63 (activation marker) after activation by the bacterial peptide formyl-methionyl-leucyl-phenylalanine (fMLP) or anti-Fcε receptor I (FcεRI) antibody and the absolute number of basophils was investigated before and after hemodialysis with each of the dialyzers. Moreover, the expression on neutrophils of CD11b, the CD11b active epitope, and CD88 was analyzed in the same groups of individuals. The expression of CD63 in basophils following activation by fMLP was significantly higher in the patient group compared with that in healthy controls, but no differences were observed after activation by anti-FcεRI. During the hemodialysis procedure, the low-flux membrane induced up-regulation of CD63 expression on basophils, while passage through the high-flux membrane did not significantly alter the responsiveness. In addition, the absolute number of basophils was unchanged after hemodialysis with either of the dialyzers and compared with healthy controls. We found no significant differences in the expression of the neutrophil activation markers (CD11b, the active epitope of CD11b, and CD88) comparing the two different dialyzers before and after dialysis and healthy controls. Together, these findings suggest that alterations in basophil activity may be a useful marker of membrane bioincompatibility in hemodialysis.
    Artificial Organs 05/2014; · 1.96 Impact Factor
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    ABSTRACT: Sarcoidosis is a systemic, inflammatory disorder, which in a proportion of patients runs a chronic progressive course despite immunosuppressive treatment. Therapeutic granulocyte and monocyte apheresis (GMA) has been shown to be an effective treatment option for other systemic inflammatory disorders, but has not yet been investigated in sarcoidosis. The aim of this study was to evaluate the response to GMA in sarcoidosis. Seven patients with sarcoidosis refractory to standard immunosuppressive therapy received ten GMA sessions. All patients underwent chest x-ray, spirometry, CRQ-SAS, blood tests and bronchoscopy with bronchoalveolar lavage (BAL) before treatment and at two-four weeks and three months (except bronchoscopy) after the last treatment session. Bronchoalveolar lavage fluid (BALF) cell differential counts were recorded and T-cells from blood and BALF were analyzed for markers of activity, differentiation and T-regulatory function. Compared to baseline, five of seven patients reported an improvement in dyspnea score. In BALF there was an increase in the percentage of macrophages and a decrease in the percentage of lymphocytes and CD4+/FoxP3+ T-cells. Furthermore, the decrease in BALF CD4+/FoxP3+ T-cells significantly correlated with an improvement in dyspnea score. In peripheral blood there was a statistically significant increase in the percentage of CD4+/CD27- T-cells and a trend towards an initial increase in the percentage of CD4+/FoxP3+ T-cells, followed by a statistically significant decrease.The effects of GMA on regulatory T-cells are consistent with that observed in other inflammatory disorders and could potentially translate into a clinical benefit.
    Clinical & Experimental Immunology 04/2014; · 3.41 Impact Factor
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    ABSTRACT: Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease, and infectious agents are suspected to be involved in the tumorigenesis of DLBCL. MicroRNAs (miRNAs) are non-coding RNAs modulating protein expression. We compared miRNA expression profiles in lymph node tissues of patients with DLBCL of the activated B-cell like (ABC) type from two geographical areas with different background exposures, Sweden and Egypt. We showed previously that DLBCL tissues of the ABC-type in Swedish patients had a higher expression of signal transducer and activator of transcription 3 (STAT3) compared to Egyptian patients. Here, we analyzed the involvement of miRNAs in STAT3 regulation. miR-1234 was significantly up-regulated in Egyptian patients with DLBCL compared to Swedish patients (p Keywords: DLBCL; STAT3; miRNA Document Type: Research Article DOI: http://dx.doi.org/10.3109/10428194.2013.824077 Affiliations: 1: 1Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden 2: 2Department of Pathology 3: 3Department of Laboratory Hematology, Toronto General Hospital, University of Health Network, Toronto, Canada 4: 5Department of Cancer Biology 5: 6Department of Clinical Immunology and Transfusion Medicine, Karolinska University Hospital, Stockholm, Sweden 6: 7Department of Medical Oncology, National Cancer Institute, Cairo University, Cairo, Egypt Publication date: May 1, 2014 More about this publication? Information for Authors Subscribe to this Title Terms & Conditions ingentaconnect is not responsible for the content or availability of external websites $(document).ready(function() { var shortdescription = $(".originaldescription").text().replace(/\\&/g, '&').replace(/\\, '<').replace(/\\>/g, '>').replace(/\\t/g, ' ').replace(/\\n/g, ''); if (shortdescription.length > 350){ shortdescription = "" + shortdescription.substring(0,250) + "... more"; } $(".descriptionitem").prepend(shortdescription); $(".shortdescription a").click(function() { $(".shortdescription").hide(); $(".originaldescription").slideDown(); return false; }); }); Related content In this: publication By this: publisher In this Subject: Allergy & Immunology By this author: Högfeldt, Therese ; Johnsson, Per ; Grandér, Dan ; Bahnassy, Abeer A. ; Porwit, Anna ; Eid, Salem ; Österborg, Anders ; Zekri, Abdel-Rahman N. ; Lundahl, Joachim ; Khaled, Mustafa Hussein ; Mellstedt, Håkan ; Moshfegh, Ali GA_googleFillSlot("Horizontal_banner_bottom");
    Leukemia and Lymphoma 01/2014; 55(5). · 2.61 Impact Factor
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    ABSTRACT: Allogeneic hematopoietic stem cell transplantation (ASCT) can be performed across the ABO blood group barrier. The impact of ABO incompatibility on clinical outcome is controversial A retrospective analysis of 310 patients that underwent ASCT with reduced intensity condition between 1998 and 2011 was performed to investigate the frequency and clinical implications of anti-Red Blood Cell (RBC) antibodies in passenger lymphocyte syndrome (PLS) after minor ABO mismatch (mm), persistent or reoccurring recipient type ABO antibodies (PRABO) after major ABO mm ASCT and autoimmune hemolytic anemia (AIHA). Transplantation characteristics and clinical outcome were analyzed by univariate and multivariate analysis for groups with or without anti-RBC antibodies. ABO blood group incompatibility did not affect clinical outcome despite an increased requirement of blood transfusion. Twelve patients with AIHA, 6 patients with PLS and 12 patients with PRABO post-ASCT were identified. AIHA did not affect overall survival (OS) or transplant related mortality (TRM) but patients with AIHA had a lower incidence of aGVHD II-IV (p=0.05). Overall survival in the PLS group was 0% compared to 61% in the whole group receiving minor ABO mm transplants (p<0.001). Comparing PRABO patients to those receiving a major ABO mm ASCT, the OS was 17% vs. 73% (p=0.002) and TRM was 50% vs. 21% (p=0.03). At our center, PLS after minor ABO mm and PRABO antibodies after major ABO mm ASCT are significant risk factors for decreased OS and TRM. Our results suggest that occurrence of unexpected ABO antibodies after ASCT warrant a wider investigation individual to find the underlying cause.
    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 11/2013; · 3.15 Impact Factor
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    ABSTRACT: Patients with chronic kidney disease (CKD) display a high prevalence of cardiovascular events and acute infections. Potential effector cells are the CD16(+) monocytes, known to be increased in the peripheral circulation in CKD. The present aim was to assess the expression of CD16 and CX3 CR1 on peripheral and in vivo extravasated monocytes in patients with CKD (GFR < 20 ml/min x 1.73 m²) using flow cytometry. In vivo extravasated monocytes were collected from a local inflammatory site, induced by a skin blistering technique. Soluble markers were assessed by Luminex. The number of CD16(+) monocytes was significantly higher in patients with CKD compared to healthy subjects, both in the peripheral circulation (p<0.05) and at the site of induced inflammation (p<0.001). Patients with CKD displayed significantly higher concentration of soluble CX3 CL1 both in the peripheral circulation (p<0.01) and in the interstitial fluid (p<0.001). In addition, patients with CKD had a significantly higher concentration of TNFα in the peripheral circulation (p<0.001). In contrary, at the inflammatory site, concentrations of both TNFα and IL-10 were significantly lower in CKD compared to in healthy controls (p<0.05 for both). In conclusion, CKD patients have an increased percentage of CD16(+) monocytes in both circulation and at the inflammatory site and this finding is in concurrence with simultaneous changes in CX3 CR1. Together with distorted TNFα and IL-10 levels this may have potential impact on the altered inflammatory response in CKD. This article is protected by copyright. All rights reserved.
    Scandinavian Journal of Immunology 09/2013; · 2.20 Impact Factor
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    ABSTRACT: BACKGROUND:: A widespread approach today is to transfuse bleeding trauma patients with RBC concentrates and plasma at a 1:1 ratio. This regime is supported by a range of observational studies showing lower mortality in bleeding patients receiving equal volumes of plasma and RBCs. The rationale for this practice is still unclear with several studies failing to show any survival benefits of increased plasma use, perhaps due to a failure to account for the timing of transfused units. OBJECTIVE:: To study the association between plasma-to-RBC ratios and risk of death in trauma patients, using appropriate methods. DESIGN, SETTINGS, AND PARTICIPANTS:: In a retrospective cohort study, we assembled data on 741 transfused trauma patients at a large trauma center. Measures of transfusion therapy were assessed entirely time dependently, and relative risk of death was compared between patients receiving low to high plasma-to-RBC ratio (< 0.85 vs > 0.85). MEASUREMENTS AND RESULTS:: In the time-dependent analyses, we saw no significant association between a low plasma ratio and the risk of death. However, age more than 75 years, injury severity score greater than 33, Glasgow Coma Scale lesser than 8, and systolic blood pressure lower than 90 mm Hg were all significantly associated with increased risk of death. Conversely, when the analyses were conducted with conventional methods, a strong protective effect of high plasma ratios was seen. CONCLUSIONS:: The key finding in our study is the strikingly different results produced by time-dependent analyses and the conventional analyses when studying survival and plasma-to-RBC ratio, supporting recent claims that prior studies showing benefit of high plasma ratios might have suffered from survival bias. There is a great need for further studies in the subject to enable improvements in treatment of massively bleeding trauma patients.
    Critical care medicine 06/2013; · 6.37 Impact Factor
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    ABSTRACT: Programmed cell death ligand-1 (PD-L1/CD274) is an immunomodulatory molecule involved in cancer and complications of bone marrow transplantation, such as graft rejection and graft-versus-host disease. The present study was designed to assess the dynamic expression of this molecule after hematopoietic stem cell transplantation in relation to acute graft-versus-host disease. Female BALB/c mice were conditioned with busulfan and cyclophosphamide and transplanted with either syngeneic or allogeneic (male C57BL/6 mice) bone marrow and splenic cells. The expression of PD-L1 was evaluated at different time points employing qPCR, western blot and immunohistochemistry. Allogeneic- but not syngeneic-transplanted animals exhibited a marked up-regulation of PD-L1 expression in the muscle and kidney, but not the liver, at days 5 and 7 post transplantation. In mice transplanted with allogeneic bone marrow cells, the enhanced expression of PD-L1 was associated with high serum levels of IFNγ and TNFα at corresponding intervals. Our findings demonstrate that PD-L1 is differently induced and expressed after allogeneic transplantation than it is after syngeneic transplantation, and that it is in favor of target rather than non-target organs at the early stages of acute graft-versus-host disease. This is the first study to correlate the dynamics of PD-L1 at the gene-, protein- and activity levels with the early development of acute graft-versus-host disease. Our results suggest that the higher expression of PD-L1 in the muscle and kidney (non-target tissues) plays a protective role in skeletal muscle during acute graft-versus-host disease.
    PLoS ONE 01/2013; 8(4):e60367. · 3.73 Impact Factor
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    ABSTRACT: Patients with chronic kidney disease (CKD) have significantly increased morbidity and mortality resulting from infections and cardiovascular diseases. Since monocytes play an essential role in host immunity, this study was directed to explore the gene expression profile in order to identify differences in activated pathways in monocytes relevant to the pathophysiology of atherosclerosis and increased susceptibility to infections. Monocytes from CKD patients (stages 4 and 5, estimated GFR <20 ml/min/1.73 m(2)) and healthy donors were collected from peripheral blood. Microarray gene expression profile was performed and data were interpreted by GeneSpring software and by PANTHER tool. Western blot was done to validate the pathway members. The results demonstrated that 600 and 272 genes were differentially up- and down regulated respectively in the patient group. Pathways involved in the inflammatory response were highly expressed and the Wnt/β-catenin signaling pathway was the most significant pathway expressed in the patient group. Since this pathway has been attributed to a variety of inflammatory manifestations, the current findings may contribute to dysfunctional monocytes in CKD patients. Strategies to interfere with this pathway may improve host immunity and prevent cardiovascular complications in CKD patients.
    PLoS ONE 01/2013; 8(7):e68937. · 3.73 Impact Factor
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    ABSTRACT: In Chronic Kidney Disease (CKD), immune cells are affected by uremic retention toxins. Given this effect, we analyzed lymphocyte proliferative response and immune modulators production following in vitro stimulation. Whole blood was drawn from healthy controls, patients with eGFR <20 ml/min/1.73 m(2) (Pre-dialysis, CKD stages 4 and 5) and hemodialysis patients (stage 5D). Peripheral cells were incubated for six days with pokeweed mitogen, concanavalin A, Staphylococcus enterotoxin A or influenza A vaccine. Peripheral lymphocyte proliferation was then analyzed by the "Flow-cytometric Assay of Specific Cell-mediated Immune response in Activated whole blood" (FASCIA) method, and cytokine profile in the cell supernatants was analyzed by the Milliplex multi-array method. The absolute number of lymphoblasts in response to mitogenic stimulation and the number of cells in each CD4+ and CD8+ subpopulation were similar comparing the three groups, except for a single decline in number of lymphoblasts after stimulation with Staphylococcus enterotoxin A, comparing dialysis patients with healthy controls. Levels of interleukin (IL)-2 (p=0.026), -10 (p=0.019) and -15 (p=0.027) in the Staphylococcus enterotoxin A-stimulated supernatant were lower in hemodialysis patients compared to healthy controls. Levels of IL-15 (p=0.017) from pre-dialysis patients and levels of IL-5 (p=0.019) from hemodialysis patients in influenza A vaccine-stimulated supernatants were also lower compared to controls. In pokeweed mitogen-stimulated supernatant, IL-2 levels (p=0.013) were lower in hemodialysis patients compared to pre-dialysis patients. TNF-α, IL-10, IL-12, IL-15, IL-8, MCP-1, IP-10, IFN-α2, IL-1α and eotaxin levels were all significantly higher in plasma obtained from CKD patients. Our results suggest that T-cells from CKD patients have similar proliferative response to stimulation compared with healthy individuals. Moreover, however the immune cells show inability to produce selected cytokines, most likely due to the uremic milieu or dialysis procedure.
    PLoS ONE 01/2013; 8(8):e73141. · 3.73 Impact Factor
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    ABSTRACT: ABSTRACT DLBCL non-Hodgkin's lymphoma is a heterogeneous disease with an association to inflammation and viral infections. We hypothesize that environmental factors may be involved in the pathogenesis of DLBCL. In this study, we compared gene expression profiles of lymph node tissues from DLBCL patients from two different geographical areas with diverse environmental exposures. Specimens from Egyptian and Swedish DLBCL patients as well as controls were studied. Gene expression analysis using micro array and quantitative PCR demonstrated significantly higher expression of STAT3 in Swedish as compared to Egyptian patients and control materials from both countries. This was confirmed at protein level using confocal microscopy. The receptor tyrosine kinase ROR1, a "survival factor" for malignant cells, was over-expressed and significantly related to the STAT3 expression pattern. The difference in the expression of genes involved in inflammatory responses and in the tumorigenic process of DLBCL might relate to infectious agents and/or other environmental exposures.
    Leukemia & lymphoma 10/2012; · 2.61 Impact Factor
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    ABSTRACT: In order to address neutrophil activation during inflammation we assessed the expression of interleukin 1 receptor type 1 (IL-1R1) following in-vivo extravasation. Extravasated neutrophils were collected from 11 healthy study subjects by a skin chamber technique and compared to neutrophils in peripheral blood. Expression of IL-1R1 was assessed by microarray, quantitative polymerase chain reaction (qPCR), Western blot, flow cytometry, enzyme linked immunosorbent assay (ELISA) and immunoelectron microscopy (iEM). IL-1R1 was induced following extravasation, demonstrated by both gene array and qPCR. Western blot demonstrated an increased expression of IL-1R1 in extravasated leucocytes. This was confirmed further in neutrophils by flow cytometry and iEM that also demonstrated an increased intracellular pool of IL-1R1 that could be mobilized by N-formyl-methionine-leucine-phenylalanine (fMLP). Stimulation of peripheral neutrophils with IL-1 resulted in transcription of NFκB and a number of downstream chemokines and the corresponding chemokines were also induced following in-vivo extravasation. The present results demonstrate that IL-1R1 is induced following extravasation and exists on the neutrophil surface, as well as in a mobile intracellular pool. Furthermore, neutrophils express functional IL-1R1 as demonstrated by the induction of chemokines following IL-1 stimulation. The results indicate a potential role for IL-1 in the activation of neutrophils at inflammatory sites.
    Clinical & Experimental Immunology 04/2012; 168(1):105-12. · 3.41 Impact Factor
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    ABSTRACT: Leukocyte apheresis primarily used for treatment of inflammatory diseases such as inflammatory bowel disease (IBD). Beside an effect of the apheresis column, the plastic lines in the apheresis system might also have an effect due to interaction between the plastic surfaces and circulating leukocytes and plasma proteins. We recently reported generation of LL-37 in the plastic lines during leukocyte adsorbing apheresis. This generation might have a positive impact on the immunologic tolerance and therefore be one operational mechanism by which the apheresis treatment executes its effect. In the present study, we report a significant generation of sIL-1RI in the apheresis lines that is initially absorbed by the LCAP device. This finding, together with our previous data on IL-1Ra indicate that important members of the IL-1 family are significantly altered during the LCAP treatment of patients with IBD. Since IL-1 and its antagonists are important for regulation of inflammatory processes in IBD, we speculate that the LCAP related changes in sIL-1RI and IL-1Ra might impact the clinical outcome. These findings have to be taken into consideration when designing new apheresis techniques as well as sham-controlled studies.
    Journal of Clinical Apheresis 01/2012; 27(2):61-3. · 2.27 Impact Factor
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    ABSTRACT: The cellular and soluble mediators of a dermal inflammation can be studied by the skin chamber technique. The aim of this study was to address the physiological effect of soluble mediators, released into the skin chamber, with special focus on neutrophil CD11b activation. Mediators released at the inflammatory site were studied by Milliplex and enzyme-linked immunosorbent assay (ELISA) and correlated with transmigration and CD11b activation in vivo and in vitro. Transmigration was studied by the skin chamber technique and by the transwell method, and expression of the CBRM1/5 epitope on activated CD11b was analysed by flow cytometry following in vivo and in vitro incubation with chamber fluid or recombinant interleukin-8 (IL-8). Leucocyte in vivo and in vitro transmigration both correlated with the concentrations of IL-1β, tumour necrosis factor alpha (TNFα) and IL-8 at P < 0.05 (R > 0.7). Furthermore, CD11b was activated, in terms of exposure of the activation epitope, on neutrophils after 30 min of in vitro incubation with chamber fluid and correlated solely with the concentration of IL-8, P < 0.05 (R = 0.72). In vitro incubation with recombinant IL-8 confirmed a concentration-dependent expression of the activation epitope; however, induction of CBRM1/5 by recombinant IL-8 required a concentration that was significantly higher compared with that in chamber fluid. In addition, the CBRM1/5 epitope was analysed on in vivo extravasated neutrophils that displayed a significantly higher expression compared with circulating neutrophils, P = 0.04. We conclude that IL-8 is the major factor regulating the expression of CD11b activation epitope in neutrophils.
    Scandinavian Journal of Immunology 01/2012; 75(4):419-25. · 2.20 Impact Factor
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    ABSTRACT: Both systemic and mucosal IgA production are controlled by T lymphocytes and infiltrating T lymphocytes are involved in the progression of interstitial fibrosis in chronic kidney disease (CKD). Since the concentration of soluble interleukin-2 receptor alfa (sIL-2Ra) reflects the degree of T cell activation over time, we studied the impact of interleukin-2 receptor alfa levels on disease progression in patients with biopsy-proven IgA nephropathy (IgAN), a disease in which 20-30% of the patients progress to end-stage renal failure. sIL-2Ra plasma levels were measured in 194 patients (median age 39 years, 70% men) and 84 matched controls. One hundred and seventy-nine of the patients, with an estimated glomerular filtration rate (GFR) of ≥15 mL/min/1.73m(2) at baseline (CKD Stages 1-4), were followed for up to 15 years (median 52 months; range 12-188). sIL-2Ra was evaluated as a risk marker for severe renal progression, here defined by the development of CKD Stage 5 (GFR <15 mL/min/1.73m(2)), a 50% decline in GFR during the follow-up period or a 30% GFR decline within 5 years of follow-up. In 51 patients, upon whom a renal biopsy had been performed within 2 years of IL2-Ra measurement, the biopsies were scored according to the Oxford classification. The correlations between the histopathological findings and the sIL-2Ra levels were examined. sIL2-Ra levels were significantly higher in patients than in controls (P < 0.001). sIL-2Ra levels in the upper third tertile predicted a severe renal outcome, even after adjustment for the main clinical risk factors: time average albuminuria and GFR at baseline (Relative risk 5.35, P < 0.001). sIL-2Ra levels also correlated significantly to the yearly GFR slope (β = -0.24, P = 0.01). According to the Oxford classification, the presence of >25% tubular atrophy/interstitial fibrosis (T1-2) was associated with higher sIL-2Ra levels, after adjustment for serum creatinine levels, if analysed within 4 months [n = 24, odds ratio (OR) 1.0, P = 0.044] or within 2 years from the kidney biopsy (n = 51, OR 1.0, P = 0.017). The plasma levels of sIL-2Ra were predictive of long-term renal disease progression in a large cohort of patients with biopsy-proven IgAN. Further studies are warranted to evaluate if sIL-2Ra levels can feasibly contribute in the monitoring of effects of treatment, aimed to prevent the progression of interstitial fibrosis and progressive glomerulosclerosis in IgAN.
    Nephrology Dialysis Transplantation 09/2011; 27(5):1916-23. · 3.37 Impact Factor
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    ABSTRACT: This study was performed to evaluate RNA extraction and gene expression analysis of non-small cell lung cancer (NSCLC) using formalin-fixed and paraffin-embedded (FFPE) specimens stored for more than 20 years by quantitative PCR (qPCR) and DNA microarrays. Long-term preserved FFPE materials enable large retrospective studies correlating molecular features with therapeutic response and clinical outcome. qPCR was used to evaluate RNA extraction methods and to compare DNA microarray gene expression profiles of FFPE and fresh frozen (FF) tissue. The Ambion RecoverAll kit appeared to be suited for RNA extraction of long-term preserved FFPE tissues. Microarray analysis using the Affymetrix platform displayed a high degree of correlation for endogenous control genes comparing FF and FFPE tissues and identified known NSCLC signature genes in both specimens. We conclude that high quality gene expression signatures can be recognized using the Affymetrix gene expression platform on FFPE tissue stored for more than 20 years. However, a general interpretation must be done with caution as different FFPE procedures have varying effects on RNA quality.
    International Journal of Oncology 04/2011; 38(4):1075-81. · 2.66 Impact Factor
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    ABSTRACT: Neutrophils from patients with chronic kidney disease (CKD) are dysfunctional and thus a contributing factor to the risk of infections. The mechanisms for leucocyte dysfunction in CKD are not fully understood. It is known that lipopolysaccharide (LPS) activates transcription of several genes encoding proinflammatory cytokines. We therefore aimed to study the effect of LPS on neutrophil expression of genes related to the inflammatory response to address the hypothesis that LPS-induced gene transcriptions are altered in CKD patients. We analysed gene expression of LPS-stimulated neutrophils from 30 patients with CKD and 15 healthy controls. Superoxide dismutase-2 (SOD2), IL1A, IL-1R1, IL-1R2 and IL8RA gene expression from both neutrophils and differentiated HL60 cells were measured by quantitative polymerase chain reaction. Differentiated HL60 cells were stimulated with phorbol-12-myristate-7-acetate (PMA) after inhibition of SOD2 by small interfering RNA followed by respiratory burst assessment using flow cytometry. LPS stimulation induced a significant mobilization of CD11b on neutrophils from CKD and healthy controls. Upregulation of SOD2, IL1A, IL-1R1 and IL-1R2 gene expression in neutrophils from healthy controls after LPS stimulation was contrasted by no change in gene transcription (IL-1R1 and IL-1R2) or even a downregulation in patients with CKD (SOD2 and IL1A). Inhibition of SOD2 reduced the PMA-induced respiratory burst and IL1A, IL-1R1, IL-1R2 and IL8RA gene expression in neutrophil-differentiated HL60 cells. Because of the critical role of SOD2 in the generation of hydrogen peroxide during phagocytosis, downregulation of SOD2 gene expression after LPS stimulation in neutrophils from patients with CKD indicates a potential mechanism for neutrophil dysfunction and cytokine dysregulation in these patients.
    Nephrology Dialysis Transplantation 11/2010; 26(7):2195-201. · 3.37 Impact Factor
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    ABSTRACT: The aim of this study was to evaluate correlations between levels of cytokines in secreted stimulated saliva in patients with chronic kidney disease (CKD) and hyposalivation. Seventy patients with clearance <20 mL/min/1.73 m(2) were evaluated; 40 were predialysis, 21 hemodialysis, and 9 peritoneal dialysis, and they were matched with 70 control subjects. Salivary flow rate was measured and submandibular/sublingual saliva collected. Analyses were performed for whole protein content using a protein assay, and levels of tumor necrosis factor (TNF) α, interleukin (IL) 1β, γ-interferon (γ-INF), IL-6, IL-8, IL-10, monocyte chemotactic protein (MCP) 1, and soluble intercellular adhesion molecule (sICAM) 1, by using Luminex technology. Patients with CKD had lower (P = .03) stimulated salivary secretion rate and higher salivary whole protein concentration (P = .002) than control subjects. Concentrations of IL-8 (P = .03) and MCP-1 (P = .002) were decreased and TNF-α/IL-10 (P = .05) and IL-8/IL10 (P = .03) ratios were decreased in CKD patients. CKD patients with low secretion levels of stimulated saliva expressed decreased levels of TNF-α (P = .04), IL-1β (P = .02), γ-INF (P = .03), IL-6 (P = .003), IL-8 (P = .005), MCP-1 (P = .006), and sICAM-1 (P = .02). Salivary cytokines and secretion rates are significantly decreased in CKD patients. Further research is necessary to understand operating mechanisms and clinical implications of the down-regulation of inflammatory markers in saliva.
    Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology 11/2010; 110(5):597-604. · 1.50 Impact Factor
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    ABSTRACT: Neutrophil transmigration can be studied in vitro by use of the transwell model and in vivo by the skin chamber model. Activation during transmigration involves translocation of secretory vesicles and granules to the plasma- and phagolysosome membranes. In this study, we compared the skin chamber model with the transwell model, focusing on the mobilization of CR1 (CD35), CR3 (CD11b/CD18) and CD63 from intracellular vesicles and granules. In addition, functional responses towards a bacterial related stimulus, formyl-methionyl-leucyl-phenylalanine (fMLP), in terms of CR3 expression and production of reactive oxygen species (ROS) were assessed. Discrepancies between the skin chamber model and the transwell model were observed. The expression of CR1 increased following in vivo transmigration (p<0.001) and, in contrast, decreased following in vitro transmigration (p=0.004). Furthermore, CR1 was mobilized following an isolation procedure included in the transwell model. The expression of CR3 increased following both in vivo (p<0.001) and in vitro (p=0.03) transmigration. However, in vitro transmigration did not influence the fMLP induced CR3 expression which was significantly increased following in vivo transmigration (p=0.01). In addition, the fMLP induced production of ROS was significantly reduced following in vitro transmigration (p=0.002) but unaltered after in vivo transmigration, indicating differences between the impact of the two systems on cellular activation. The observed discrepancies between the two models might be partly explained by granule mobilization and neutrophil priming, induced during the isolation procedure included in the transwell model, which results in an altered cellular activation. Therefore, mobilization of granules needs to be accounted for when interpreting data from different model systems.
    Journal of immunological methods 09/2010; 361(1-2):82-8. · 2.35 Impact Factor
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    ABSTRACT: Peritonitis is a common and serious complication of peritoneal dialysis (PD). Coagulase-negative staphylococci from the patient's own skin flora are the most commonly found micro-organisms. In the present study we aim to elucidate the immune response in the early stage of infection and to clarify the importance of bacterial attachment to fibrinogen. Clinical Staphylococcus epidermidis isolates collected from PD peritonitis or the residential skin flora of healthy individuals were used to infect monocytes, macrophages, and peripheral blood mononuclear cells (PBMC) in the presence or absence of fibrinogen. The S. epidermidis strain HB (fbe(+)), expressing the fibrinogen-binding protein Fbe, and its isogenic mutant ST056 (fbe(-)) were used to study the impact of Fbe during cell infection. Immune induction was measured as interleukin-8 (IL-8) production determined by ELISA. Modulation of CD11b/CD18 expression in neutrophils incubated in conditioned medium from these experiments was analyzed in order to judge the cellular response. S. epidermidis causing peritonitis was less immunogenic compared to strains belonging to the residential skin flora, as measured by IL-8 induction in monocytes and CD11b/CD18 expression in neutrophils. At low bacterial concentrations, attachment to fibrinogen was a prerequisite for an IL-8 induction in monocytes and PBMC. The fibrinogen-binding protein Fbe did not, however, influence immune induction under this condition. We suggest that S. epidermidis strains may be able to cause clinical infection by evoking an inadequate immunological response in the early stage of infection. Bacterial attachment to fibrinogen is a relevant event during this phase but independent of the fibrinogen-binding protein Fbe.
    Peritoneal dialysis international : journal of the International Society for Peritoneal Dialysis. 05/2010; 31(6):672-8.

Publication Stats

2k Citations
579.82 Total Impact Points

Institutions

  • 1991–2014
    • Karolinska University Hospital
      • Department of Clinical Immunology and Transfusion Medicine
      Tukholma, Stockholm, Sweden
  • 1992–2013
    • Karolinska Institutet
      • • Institutionen för laboratoriemedicin
      • • Institutionen för medicin, Huddinge
      • • Institutionen för onkologi-patologi
      • • Klinisk immunologi & transfusionsmedicin
      Stockholm, Stockholm, Sweden
    • Akademiska Sjukhuset
      Uppsala, Uppsala, Sweden
  • 2012
    • Uppsala University
      Uppsala, Uppsala, Sweden
  • 2010
    • Skåne University Hospital
      Malmö, Skåne, Sweden
  • 2009
    • Malmö University
      Malmö, Skåne, Sweden
  • 1999–2000
    • McMaster University
      • • Department of Medicine
      • • Division of Clinical Immunology and Allergy
      Hamilton, Ontario, Canada
  • 1996–1997
    • Linköping University
      • Faculty of Health Sciences
      Linköping, OEstergoetland, Sweden
  • 1995–1996
    • University Hospital Linköping
      Linköping, Östergötland, Sweden