S S Frøland

University of Oslo, Kristiania (historical), Oslo, Norway

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Publications (219)766.44 Total impact

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    ABSTRACT: Patients with common variable immunodeficiency (CVID) have reduced numbers and frequencies of dendritic cells (DCs) in blood, and there is also evidence for defective activation through toll-like receptors (TLRs). Collectively, these observations may point to a primary defect in the generation of functional DCs. Here, we measured frequencies of plasmacytoid DCs (pDCs) and myeloid DCs (mDCs) in peripheral blood of 26 CVID patients and 16 healthy controls. The results show that the patients have reduced absolute counts of both subsets. However, the decreased numbers in peripheral blood were not reflected in reduced frequencies of CD34(+) pDC progenitors in the bone marrow. Moreover, studies at the single cell level showed that DCs from CVID patients and healthy controls produced similar amounts of interferon-α or interleukin-12 and expressed similar levels of activation markers in response to human cytomegalovirus and ligands for TLR7 and TLR9. The study represents the most thorough functional characterization to date, and the first to assess bone marrow progenitor output, of naturally occurring DCs in CVID. In conclusion, it seems unlikely that CVID is secondary to insufficient production of naturally occurring DCs or a defect in their signalling through TLR7 or TLR9.
    No preview · Article · Nov 2013 · Clinical & Experimental Immunology
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    ABSTRACT: The aim of the study was to investigate immunoglobulin levels in patients with epilepsy using the antiepileptic drugs (AED) levetiracetam (LEV), carbamazepine (CBZ), or lamotrigine (LTG). A total of 211 patients and 80 controls (age: 18-45 years) of both genders were included. The patients had been treated with either LEV (n = 47), CBZ (n = 90), or LTG (n = 74) monotherapy for at least 6 months. Total concentrations of immunoglobulin G (IgG), IgG subclasses (IgG1, IgG2, IgG3, and IgG4), immunoglobulin A (IgA), and immunoglobulin M (IgM) were measured. Smoking, drinking habits, and physical activity were recorded, and body mass index (BMI) was calculated. A significantly lower total IgG and IgG1 was found in both men and women treated with LTG and in men on CBZ. IgG2 and IgG4 were also lower in LTG-treated women, and IgA and IgM were lower in LTG-treated men. Patients treated with LEV did not differ from the control group. Low levels of immunoglobulins were found in patients with epilepsy treated with LTG or CBZ. As our group of patients consisted of otherwise healthy young adults, one should be especially aware of a possible effect of AEDs on immunoglobulin levels when treating selected patient groups, for example immunocompromised patients. Immunoglobulin concentrations should be measured in patients treated with LTG or CBZ who experience recurrent infections, and a change in medication should be considered.
    No preview · Article · Jan 2013 · Acta neurologica Scandinavica. Supplementum
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    ABSTRACT: Based on the ability to recruit lymphocytes and dendritic cells to lymphoid tissue and to promote inflammation, we hypothesized a role for dysregulated CCL19 and CCL21 levels in human immunodeficiency virus (HIV)-infected patients with advanced immunodeficiency, and in particular in those with accompanying Mycobacterium avium complex (MAC) infection. The hypothesis was explored by studies in HIV-infected patients with and without MAC infection, as well as in vitro, examining the ability of proteins from MAC to promote CCL19 and CCL21 responses in peripheral blood mononuclear cells (PBMC) during highly active anti-retroviral therapy (HAART). Our main findings were: (i) raised serum levels of CCL19 in HIV-infected patients with CD4(+) T cell count <50 cells/µl compared with HIV-infected patients with CD4(+) T cell count >500 cells/µl and healthy controls, with particularly high levels in those with MAC infection; (ii) elevated plasma levels of CCL19 predicted a higher mortality in acquired immune deficiency syndrome (AIDS)-patients, independent of ongoing MAC infection; and (iii) marked production of CCL19 in MAC-stimulated peripheral blood mononuclear cells (PBMC) and pronounced disturbances in MAC-induced CCL19 production in PBMC from HIV patients that was partly reversed during HAART. Our findings suggest the involvement of CCL19 in AIDS patients with advanced immunodeficiency, potentially mediating both adaptive and maladaptive responses.
    Full-text · Article · Mar 2012 · Clinical & Experimental Immunology
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    L Landrø · T Ueland · K Otterdal · S S Frøland · P Aukrust

    Full-text · Article · Feb 2011 · Journal of Thrombosis and Haemostasis
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    J D Capra · S S Frøland · M Harboe · R Jonsson · H-G Ljunggren · H Wigzell

    Full-text · Article · Dec 2009 · Scandinavian Journal of Immunology
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    ABSTRACT: While some chemokines are thought to be protective in HIV-infected individuals by their ability to block HIV entry into T cells and macrophages, chemokines could also have harmful effects in HIV infection through their ability to promote inflammation. Here, we examined the regulation and the effects of CXCL16, a newly discovered chemokine of the CXC family, in HIV-infected patients. We examined serum levels of CXCL16 in clinically well-defined subgroups of HIV-infected individuals both before (n = 62) and during HAART (n = 40) as well as in age- and sex-matched healthy controls (n = 30). We also examined the effects of CXCL16 on inflammatory and anti-inflammatory cytokines and HIV replication in peripheral blood mononuclear cells (PBMC). Our main and novel findings were: (i) HIV-infected patients had significant raised CXCL16 levels according to disease severity and progression. (ii) During HAART, the immunological improvement was accompanied by a modest increase in CXCL16 level. (iii) While soluble CXCL16 promoted an anti-inflammatory response in PBMC from those on successful HAART, it induced an inflammatory response and enhanced HIV replication in PBMC from those with high viral load irrespectively of ongoing HAART. (iv) Recombinant HIV-tat protein significantly increased CXCL16 release in THP-1 macrophages. Our findings suggest a complex interaction between CXCL16 and HIV, promoting both inflammatory and anti-inflammatory effects as well as HIV replication, partly dependent on accompanying HIV replication.
    No preview · Article · Sep 2009 · European Journal of Clinical Investigation
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    ABSTRACT: CCL19 and CCL21 and their receptor CCR7 are expressed constitutively within lymphoid organs, regulating lymphocyte homing. Recent studies suggest that these chemokines may have inflammatory properties. We hypothesized a role of CCL19/CCL21 in human immunodeficiency virus (HIV) infection by promoting inflammation. We examined the expression of CCL19 and CCL21 in mononuclear cells from peripheral blood mononuclear cells (PBMC) and bone marrow mononuclear cells (BMMC) in HIV-infected patients before and during highly active anti-retroviral therapy (HAART). We also examined the ability of CCL19/CCL21 to promote inflammatory responses in these patients. PBMC from untreated HIV-infected patients (n = 29) released enhanced levels of CCL19 spontaneously compared with cells from controls (n = 20), particularly in those with symptomatic disease (n = 15, P < 0.01 versus controls). During HAART (n = 9), there was a decrease in the spontaneous CCL19 release and an increase in the phytohaemagglutinin-stimulated CCL19 release in both PBMC (P < 0.01) and BMMC (P < 0.05). In patients with enhanced HIV replication there was an increased proportion of inflammatory CD8(+)CCR7(-)CD45RA(-) T cells in peripheral blood [P < 0.01 and P < 0.05 versus controls, untreated (n = 9) and treatment failure (n = 8), respectively]. In vitro, CCL19/CCL21 promoted an inflammatory response in PBMC when accompanied by high viral load, irrespective of HAART. The HIV-tat protein significantly boosted the inflammatory effect of CCL19/CCL21 in PBMC. These findings link a dysregulated CCL19/CCL21/CCR7 system in HIV-infected patients to persistent inflammation and HIV replication, not only in untreated HIV infection, but also in treatment failure during HAART.
    Full-text · Article · Sep 2009 · Clinical & Experimental Immunology
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    ABSTRACT: Common variable immunodeficiency (CVID) is a heterogeneous syndrome characterized by defective immunoglobulin production and high frequency of bacterial infections, autoimmunity and manifestations of chronic inflammation. The homeostatic chemokines CCL19 and CCL21 and their receptor CCR7 are associated with modulation of inflammatory responses. CVID patients have decreased proportions of CCR7(+) T cells in peripheral blood and we hypothesized a further dysregulation of CCL19/CCL21/CCR7 in CVID. Serum levels of CCL19 and CCL21 were compared in CVID patients and controls. T cell expression of CCR7 was related to clinical characteristics in CVID patients. Spleens extirpated from CVID patients were analysed for expression of CCL19, CCL21 and CCR7. Peripheral blood mononuclear cells (PBMC) from CVID patients and controls were analysed for cytokine response on stimulation with CCL19 and CCL21. The main findings were: (i) CVID patients have raised serum levels of CCL19 and CCL21 independently of features of chronic inflammation; (ii) CCL19 and CCR7 have similar expression in spleens from CVID patients and controls, while CCL21 is variably down-regulated in spleens from patients; (iii) T cell expression of CCR7 is particularly low in patients characterized by chronic inflammation in vivo; and (iv) PBMC from CVID patients had attenuated cytokine response to stimulation with CCL19 and CCL21. CVID patients have raised circulatory levels of CCL19 and CCL21, and an attenuated cytokine response to stimulation with these chemokines. Because CCR7, CCL19 and CCL21 are key mediators balancing immunity and tolerance in the immune system, the abnormalities of these mediators might contribute to the profound immune dysregulation seen in CVID.
    Full-text · Article · Aug 2009 · Clinical & Experimental Immunology
  • P Berdal · P Brandtzaeg · S S Froland · S D Henriksen · S Skrede
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    ABSTRACT: Among patients with recurrent, protracted or chronic infections of the respiratory tract involving the middle ear, 18 were found to have immunodeficiencies. In 10 of the patients, deficiency of immunoglobulins belonging to the IgG, IgA and IgM classes was found. Seven patients had an isolated IgA deficiency. One patient had a combined immunodeficiency with defects of the T-cell system and the B-cell system. One patient had an isolated T-cell deficiency. © 1976 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.
    No preview · Article · Jul 2009 · Acta Oto-Laryngologica
  • S Gregersen · B Fevang · J Kongerud · P Aukrust · SS Froland · B Johansen

    No preview · Conference Paper · Apr 2009
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    ABSTRACT: Expression of the γ/δ T cell receptor (TCR) on CD3+ intracpithclial lymphocytes (IELs) was studied by two-colour immunofluorescence in duodenal tissue sections from healthy (n= 6) or infection-prone (n = 7) subjects with selective IgA deficiency (IgAD), and subjects (n= 4) with combined IgAD and IgG subclass deficiency. TCRγ/δ+ IEL proportions in selective IgAD subjects (median 6.3%, range 1.0–41%) and in those with combined deficiency (median 4.5%, range 1±2.33%) were well within the range (0.3.38%) for histologically normal controls (n= 11), but the healthy IgAD subgroup tended to show raised TCRγ/δ+ IEL proportions (median 13.6%) compared with the other two subgroups. Also the number of TCRγ/δ+ IELs per intestinal length unit was relatively high (median 13.9/mm) in the healthy IgAD subjects, and significantly raised (P < 0.03) compared with controls (median 3.2/mm). Paired staining revealed that most TCRγ/δ+ IELs in both selective IgAD (98%) and combined deficiency (99%) were CD8, and a large fraction (median 84% and 63%, respectively) expressed the Vδ1/Jδ1-encoded epitope. The total number of CD3’ IELs (mostly CD8+) was similar to controls. IgAD subjects, and especially the healthy subgroup, had significantly increased serum concentrations of soluble CD8 (P < 0.0002), neopterin (P < 0.005), and β2-microglobulin (P < 0.007). which was similar to our previous observations in common variable immunodeficiency, and probably reflected stimulation of cell-mediated immunity. In addition, the increased TCRγ/δ+ IELs might reflect a component of compensatory surface protection in the healthy IgAD subgroup.
    Full-text · Article · Oct 2008 · Clinical & Experimental Immunology

  • No preview · Article · May 2008 · Atherosclerosis Supplements
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    ABSTRACT: Although neutrophil gelatinase-associated lipocalin (NGAL) may play a pivotal role in the innate immune response, there are currently no data on NGAL levels in human immunodeficiency virus (HIV)-infected patients. In this study we aimed to examine the regulation of NGAL in HIV infection. The regulation of NGAL in HIV infection was examined by different experimental approaches, including studies in peripheral blood and mononuclear cells (MNC) from bone marrow aspirates before and during highly active anti-retroviral therapy (HAART). We found that: before initiating HAART, HIV-infected patients (n = 37) had significantly decreased serum NGAL levels compared with healthy controls (n = 26); (ii) during HAART, there was a gradual and significant increase in NGAL concentrations reaching levels comparable to those in healthy controls after 12 months; (iii) this increase was seen primarily in virological responders to HAART (HIV RNA level <200 copies/ml after 24 months); (iv) phytohaemagglutinin-stimulated NGAL release in MNC cells from bone marrow aspirates was decreased in untreated HIV-infected patients compared with healthy controls, but increased after 26 weeks on HAART; and (v) there was a significant positive correlation between neutrophil counts and NGAL levels at all time-points during HAART. We have shown decreased NGAL levels in HIV-infected patients, potentially reflecting decreased number and function of neutrophils as well as impaired bone marrow myelopoiesis. These abnormalities were reversed by successful HAART. Our findings underscore further the involvement of neutrophils and innate immunity in HIV-related immunodeficiency.
    Full-text · Article · May 2008 · Clinical & Experimental Immunology
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    B Fevang · A Yndestad · W J Sandberg · A M Holm · F Müller · P Aukrust · S S Frøland
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    ABSTRACT: Common variable immunodeficiency (CVID) is a heterogeneous syndrome characterized by defective immunoglobulin production and high frequency of bacterial infections, autoimmunity and manifestations of chronic inflammation. Abnormalities of CD4+CD25high forkhead box P3 (FoxP3)+ regulatory T cells (Treg) have been associated with autoimmune and inflammatory disorders, and we hypothesized that CVID might be characterized by Treg abnormalities. CD3+ cells from patients and controls were analysed for the expression of FoxP3 mRNA by real time reverse transcription-polymerase chain reaction (RT-PCR). Peripheral blood mononuclear cells from CVID patients and controls were stained for Treg markers, analysed by flow cytometry and compared to clinical characteristics. The main findings were: (i) CVID patients had significantly decreased expression of FoxP3 mRNA and decreased proportions of CD4+CD25highFoxP3+ cells compared to controls; (ii) CVID patients with splenomegaly had even lower proportions of Treg compared to other patients and controls; (iii) serum levels of the inflammatory marker neopterin were correlated negatively with the proportions of Treg within the CVID population, while there was no significant association with bronchiectasis. We have demonstrated decreased proportions of Treg in CVID patients, particularly in those with signs of chronic inflammation. Decreased proportions of TReg are suggested to be pathogenetically important in autoimmunity, and our results suggest that TReg may have a similar role in CVID.
    Full-text · Article · Apr 2007 · Clinical & Experimental Immunology
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    ABSTRACT: Chemokines and platelet activation are both important in atherogenesis. Platelet inhibitors are widely used in coronary artery disease (CAD), and we hypothesized that the platelet inhibitor clopidogrel could modify chemokines in CAD patients. We sought to investigate the effect of clopidogrel on the expression of chemokines and chemokine receptors in peripheral blood mononuclear cells (PBMC) in CAD patients. Patients/methods: Thirty-seven patients with stable angina were randomized to clopidogrel (n = 18) or placebo (n = 19). PBMC, blood platelets and plasma were collected at baseline and after 7-10 days in the patients, and in 10 healthy controls. mRNA levels of chemokines and chemokine receptors in PBMC were analyzed by ribonuclease protection assays and real-time reverse transcriptase polymerase chain reaction. Platelet activation was studied by flow cytometry. (i) At baseline, the gene expression of the regulated on activation normally T-cell expressed and secreted (RANTES) chemokines and macrophage inflammatory peptide (MIP)-1beta in PBMC, the expression of CD62P and CD63 on platelets and the levels of platelet-derived microparticles (PMP) were elevated in angina patients comparing healthy controls; (ii) markers of platelet activation were either reduced (CD63) or unchanged (CD62P, PMP, beta-thromboglobulin) during clopidogrel therapy; (iii) in contrast, clopidogrel significantly up-regulated the gene expression of RANTES and MIP-1beta in PBMC, while no changes were found in the placebo group; (iv) a stable adenosine 5'-diphosphate metabolite attenuated the release of MIP-1beta, but not of RANTES, from activated PBMC in vitro. Even if we do not argue against a beneficial role for clopidogrel in CAD, our findings may suggest potential inflammatory effects of clopidogrel in CAD.
    Full-text · Article · Nov 2006 · Journal of Thrombosis and Haemostasis
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    A M Holm · G Tjønnfjord · A Yndestad · K Beiske · F Müller · P Aukrust · S S Frøland
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    ABSTRACT: Common variable immunodeficiency (CVID) is the most frequent symptomatic primary immunodeficiency disease, characterized by low levels of circulating immunoglobulins and recurrent bacterial infections, particularly of the respiratory tract. T cell dysfunction is often present, and lymphoproliferative and autoimmune disorders as well as haematological cytopenias are frequently observed. In this study, we report a polyclonal expansion of large granular lymphocytes (LGL) in a substantial proportion of CVID patients, associated with splenomegaly, increased numbers of CD8(+) T cells, inverted CD4 : CD8 T cell ratios and neutropenia. CVID patients who had both increased numbers of LGL and granulocytopenia had elevated levels of soluble Fas ligand (sFasL). Our observations indicate that CVID may be added to the list of inflammatory diseases associated with increased numbers of LGL. Furthermore, our findings suggest common pathogenic mechanisms of granulocytopenia in CVID and lymphoproliferative disease of granular lymphocytes.
    Full-text · Article · Jul 2006 · Clinical & Experimental Immunology
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    ABSTRACT: Idiotypic antisera were raised in rabbits against serum M-cnmponents in two patients with chronic lymphocytic leukemia (CLL) In one of the patients the leukemic cells had membrane-bound IgG. in the other IgM and IgD. The M-components were IgG and IgM. respectively. By immunofluorescence technique the CLL cells were shown to be positive when stained with idiotypic antiserum prepared against the corresponding M component, whereas normal lymphocytes, as well as cells from other CLL patients, were negative. These findings represent strong evidence for the monoclonality of the malignant B cells in CLL The fact that the CLL cells had membrane-bound Ig with the same idiotypic determinants as the corresponding serum M-component indicated that the latter had been synthesized and secreted by the malignant clone of B cells. In further experiments redistribution of membrane-bound Ig on CLL cells bearing both IgM and IgD was induced with idiotypic antiserum This indicated that IgM and IgD on the same cells share idiotypic specificity and therefore have the same variable region and. presumably, the same antibody specificity
    No preview · Article · Jun 2006 · Scandinavian Journal of Immunology

  • No preview · Article · Jun 2006 · Scandinavian Journal of Immunology
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    ABSTRACT: Mannose-binding lectin (MBL) is a soluble receptor of the innate immune system, probably contributing to antimicrobial defence. The possible role of MBL in HIV infection is unclear. Peripheral blood mononuclear cells (PBMCs) from 28 HIV-infected patients and 13 healthy controls were stimulated with MBL and costimulated with HIV-1 gp120 or mannan from Saccharomyces cerevisiae before inflammatory responses in PBMC cultures were examined by enzyme-linked immunosorbent assay (ELISA) and flow cytometry. HIV-1 RNA replication in vitro was assessed by quantitative reverse transcription polymerase chain reaction (RT-PCR) in supernatants from patients with measurable HIV-1 RNA levels. (i) Enhanced TNF-alpha responses were observed when PBMCs from healthy controls and HIV-infected patients were stimulated with MBL and costimulated with HIV-1 gp120 or mannan. (ii) MBL stimulation induced increased HIV RNA replication in culture supernatants when costimulated with mannan. The present study suggests a modulatory role of MBL on cytokine responses, and HIV replication after stimulation with microbial products. These effects of MBL on inflammatory responses and viral replication may be clinically relevant for HIV infection.
    No preview · Article · Jan 2006 · European Journal of Clinical Investigation
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    ABSTRACT: The importance of the innate immune system, including mannose-binding lectin and the complement system, in common variable immunodeficiency is unclear. The objective of this study was to evaluate mannose-binding lectin and the complement system in relation to clinical and immunological parameters in patients with common variable immunodeficiency. Circulating levels of mannose-binding lectin, complement components, complement activation products and functional capacity of complement pathways were correlated to clinical features within 71 patients and compared with 30 healthy controls. The main findings were; the patients had signs of increased complement activation significantly associated with signs of autoimmunity and immunological hyperactivity; there were no signs of deficiencies of the classical and alternative complement pathways in the patient group; the prevalence of lectin pathway deficiency was the same in patients and controls, but patients with increased frequency of lower respiratory tract infections or bronchiectasis had lower capacity of the lectin pathway than patients without these features (P = 0.002 and 0.004, respectively); the serum concentration of mannose-binding lectin was inversely correlated to the frequency of lower respiratory tract infections (P = 0.002) and bronchiectasis (P = 0.01). We conclude that patients with common variable immunodeficiency have no increased frequency of complement deficiencies but signs of increased complement activation. Our findings suggest that mannose-binding lectin and the lectin complement pathway may protect against lower respiratory tract infection and bronhiectasis in patients with common variable immunodeficiency.
    Full-text · Article · Jan 2006 · Clinical & Experimental Immunology

Publication Stats

6k Citations
766.44 Total Impact Points


  • 1973-2013
    • University of Oslo
      • • Faculty of Medicine
      • • Research Institute for Internal Medicine (IIM)
      • • Division of Medicine
      • • Division of Surgery
      • • Department of General Internal Medicine
      • • Department of Ophthalmology (OPHT)
      • • Department of Paediatrics
      Kristiania (historical), Oslo, Norway
  • 1972-2009
    • Oslo University Hospital
      • • Department of Microbiology
      • • Research Institute of Internal Medicine
      Kristiania (historical), Oslo County, Norway
    • Armauer Hansen Research Institute
      Ādīs Ābeba, Ādīs Ābeba, Ethiopia
  • 1999-2001
    • Diakonhjemmet Hospital (Norway)
      Kristiania (historical), Oslo, Norway
  • 1997
    • Norwegian University of Science and Technology
      Nidaros, Sør-Trøndelag, Norway
  • 1995
    • Copenhagen University Hospital Hvidovre
      • Department of Pathology
      Hvidovre, Capital Region, Denmark
  • 1993
    • Institutt for samfunnsforskning, Oslo
      Kristiania (historical), Oslo County, Norway
  • 1976-1977
    • Karolinska Institutet
      • Department of Medicine, Huddinge
      Solna, Stockholm, Sweden
    • The American University of Rome
      Roma, Latium, Italy
    • University of Bergen
      Bergen, Hordaland, Norway