uu.seUppsala University Publications
Change search
Refine search result
1 - 9 of 9
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the Create feeds function.
  • 1.
    Hagberg, Niklas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Theorell, Jakob
    Hjorton, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Spee, Pieter
    Eloranta, Maija-Leena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Bryceson, Yenan T.
    Rönnblom, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Functional Anti-CD94/NKG2A and Anti-CD94/NKG2C Autoantibodies in Patients With Systemic Lupus Erythematosus2015In: ARTHRITIS & RHEUMATOLOGY, ISSN 2326-5191, Vol. 67, no 4, p. 1000-1011Article in journal (Refereed)
    Abstract [en]

    Objective. Recently we serendipitously identified a patient with systemic lupus erythematosus (SLE) who was positive for autoantibodies to CD94/natural killer receptor group 2A (NKG2A). The present study was undertaken to investigate the occurrence and function of autoantibodies targeting lectin-like NK cell receptors in SLE. Methods. Sera from 203 SLE patients and 90 healthy individuals were analyzed, by flow cytometry, for Ig binding to Ba/F3 cells transfected with CD94/NKG2A, CD94/NKG2C, or NKG2D. Autoantibodies identified were characterized with regard to interference with HLA-E binding, effect on NK cell activation in response to HLA-E-transfected K562 cells, and capacity to facilitate antibody-dependent cell-mediated cytotoxicity (ADCC). Levels of autoantibodies were determined in longitudinally sampled sera, and correlations with disease activity (SLE Disease Activity Index 2000) and severity (Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index) were investigated. Results. Anti-CD94/NKG2A autoantibodies were identified in 7 SLE patients. The autoantibodies from 6 patients inhibited binding of HLA-E to CD94/NKG2A, whereas those from the seventh patient augmented this binding. Autoantibodies from 2 patients also reacted with the activating receptor CD94/NKG2C, with inhibition of the binding of HLA-E to CD94/NKG2C observed in 1 case and enhancement of this binding in the other. None of the sera contained anti-NKG2D autoantibodies. The levels of anti-CD94/NKG2A and anti-CD94/NKG2C autoantibodies correlated with disease activity and with a more severe SLE phenotype. Mechanistically, anti-CD94/NKG2A and anti-CD94/NKG2C autoantibodies both interfered with HLA-E-mediated regulation of NK cell activation and facilitated the elimination of target cells expressing CD94/NKG2A or CD94/NKG2C through ADCC. Conclusion. Anti-CD94/NKG2A and anti-CD94/NKG2C autoantibodies occur in a subset of patients with clinically active SLE. Given their capacity to deplete certain NK cell subsets and interfere with particular NK cell function, such autoantibodies may promote the pathogenesis of SLE.

  • 2.
    Hellbacher, Erik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Hjorton, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Backlin, Carin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Enblad, Gunilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Sundström, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Baecklund, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Knight, Ann
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Malignant lymphoma in granulomatosis with polyangiitis: subtypes, clinical characteristics and prognosis2019In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 58, no 11, p. 1655-1659Article in journal (Other academic)
    Abstract [en]

    Several autoimmune and inflammatory conditions, such as rheumatoid arthritis (RA) and primary Sjögrens’s syndrome (pSS), have repeatedly been linked to an increased risk of malignant lymphoma [1,2]. Certain inflammatory conditions are also associated with the development of specific lymphoma subtypes such as mucosa-associated lymphoid tissue (MALT) lymphoma in pSS and diffuse large B-cell lymphoma (DLBCL) in RA. The underlying mechanisms behind this association remain unclear. The highly increased risk of developing MALT lymphoma of the parotid gland in pSS indicates that local inflammatory processes can promote lymphoma development at the site of chronic inflammation [3]. In RA, an association between disease severity and risk of lymphoma has been shown.

    Granulomatosis with polyangiitis (GPA), formerly Wegener’s granulomatosis, is a systemic small vessel vasculitis associated with the presence of anti-neutrophil cytoplasmic antibodies (ANCA) and characterized by granulomatous inflammation and necrotizing vasculitis of the airways and kidneys but possibly affecting any organ system. An increased risk of lymphoma in patients with GPA has been reported in several epidemiological studies [4,5]. However, very little is known about risk factors for lymphoma development in this group, possible relation to disease severity, treatment and lymphoma subtypes or the prognosis for the lymphomas. This is the first published study on GPA and lymphoma, giving detailed information on the GPA characteristics and possible risk factors for lymphoma and also lymphoma subtypes treatment and survival.

  • 3.
    Hellbacher, Erik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Hjorton, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Sundström, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Baecklund, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Knight, Ann
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Malignant Lymphoma In Granulomatosis With Polyangiitis2017In: Rheumatology, ISSN 1462-0324, E-ISSN 1462-0332, Vol. 56Article in journal (Refereed)
  • 4.
    Hjorton, Karin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Hagberg, Niklas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Berggren, Olof
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Mo, J.
    AstraZeneca R&D, Mölndal, Sweden.
    Sandling, Johanna K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Eloranta, Maija-Leena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Rönnblom, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    The Effect of Hydroxychloroquine and IRAK4 Inhibition on The IFN-A and TNF-A Production Induced by Sle Related Immune Complexes2016In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 75, p. 277-277Article in journal (Other academic)
  • 5.
    Hjorton, Karin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Hagberg, Niklas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Israelsson, E.
    AstraZeneca, Innovat Med & Early Dev Biotech Unit, Biosci Resp Inflammat & Autoimmun, Gothenburg, Sweden.
    Berggren, Olof
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Sandling, Johanna K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Thorn, K.
    AstraZeneca, Innovat Med & Early Dev Biotech Unit, Biosci Resp Inflammat & Autoimmun, Gothenburg, Sweden.
    Mo, J.
    AstraZeneca, Innovat Med & Early Dev Biotech Unit, Biosci Resp Inflammat & Autoimmun, Gothenburg, Sweden.
    Eloranta, M. -L
    Rönnblom, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Cytokine production by activated plasmacytoid dendritic cells and NK cells is suppressed by an IRAK4 inhibitor2018In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 77, p. 1268-1269Article in journal (Other academic)
  • 6.
    Hjorton, Karin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Hagberg, Niklas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Israelsson, Elisabeth
    AstraZeneca, IMED Biotech Unit, Resp Inflammat & Autoimmun, Gothenburg, Sweden.
    Jinton, Lisa
    AstraZeneca, IMED Biotech Unit, Resp Inflammat & Autoimmun, Gothenburg, Sweden.
    Berggren, Olof
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Sandling, Johanna K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Thörn, Kristofer
    AstraZeneca, IMED Biotech Unit, Resp Inflammat & Autoimmun, Gothenburg, Sweden.
    Mo, John
    AstraZeneca, IMED Biotech Unit, Resp Inflammat & Autoimmun, Gothenburg, Sweden.
    Eloranta, Maija-Leena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab. SciLifeLaboratory.
    Rönnblom, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Cytokine production by activated plasmacytoid dendritic cells and natural killer cells is suppressed by an IRAK4 inhibitor2018In: Arthritis Research & Therapy, ISSN 1478-6354, E-ISSN 1478-6362, Vol. 20, article id 238Article in journal (Refereed)
    Abstract [en]

    Background: In systemic lupus erythematosus (SLE), immune complexes (ICs) containing self-derived nucleic acids trigger the synthesis of proinflammatory cytokines by immune cells. We asked how an interleukin (IL)-1 receptor-associated kinase 4 small molecule inhibitor (IRAK4i) affects RNA-IC-induced cytokine production compared with hydroxychloroquine (HCQ).

    Methods: Plasmacytoid dendritic cells (pDCs) and natural killer (NK) cells were isolated from peripheral blood mononuclear cells (PBMCs) of healthy individuals. PBMCs from SLE patients and healthy individuals were depleted of monocytes. Cells were stimulated with RNA-containing IC (RNA-IC) in the presence or absence of IRAK4i I92 or HCQ, and cytokines were measured by immunoassay or flow cytometry. Transcriptome sequencing was performed on RNA-IC-stimulated pDCs from healthy individuals to assess the effect of IRAK4i and HCQ.

    Results: In healthy individuals, RNA-IC induced interferon (IFN)-α, tumor necrosis factor (TNF)-α, IL-6, IL-8, IFN-γ, macrophage inflammatory protein (MIP)1-α, and MIP1-β production in pDC and NK cell cocultures. IFN-α production was selective for pDCs, whereas both pDCs and NK cells produced TNF-α. IRAK4i reduced the pDC and NK cell-derived cytokine production by 74–95%. HCQ interfered with cytokine production in pDCs but not in NK cells. In monocyte-depleted PBMCs, IRAK4i blocked cytokine production more efficiently than HCQ. Following RNA-IC activation of pDCs, 975 differentially expressed genes were observed (false discovery rate (FDR) < 0.05), with many connected to cytokine pathways, cell regulation, and apoptosis. IRAK4i altered the expression of a larger number of RNA-IC-induced genes than did HCQ (492 versus 65 genes).

    Conclusions: The IRAK4i I92 exhibits a broader inhibitory effect than HCQ on proinflammatory pathways triggered by RNA-IC, suggesting IRAK4 inhibition as a therapeutic option in SLE.

  • 7.
    Hjorton, Karin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Hellbacher, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Sundstrom, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Baecklund, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Knight, Ann
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Lymphoma in Patients with Granulomatosis with Polyangiitis2015In: Arthritis & Rheumatology, ISSN 2326-5191, E-ISSN 2326-5205, Vol. 67, no Suppl 10, article id 869Article in journal (Other academic)
  • 8.
    Knight, Ann
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Hjorton, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Sundström, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Höglund, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Backlin, Carin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Smedby, Karin E
    Askling, Johan
    Baecklund, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Leukemia and Myelodysplastic Syndrome in Granulomatosis with Polyangiitis: Subtypes, Clinical Characteristics, and Outcome2015In: Journal of Rheumatology, ISSN 0315-162X, E-ISSN 1499-2752, Vol. 42, no 4, p. 690-694Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Previous studies have shown that patients with granulomatosis with polyangiitis (GPA) have an increased risk of hematological malignancies, especially leukemia. Our aim was to assess clinical characteristics and treatment of patients with GPA complicated by hematological malignancies with focus on leukemia and to describe these malignancies in more detail.

    METHODS: From the Swedish population-based patient register, all individuals with a diagnosis of GPA from 1964-2012 were identified (n = 3224). Through linkage with the Swedish Cancer Register, we searched for all cases of leukemia [International Classification of Diseases (ICD) 7: 204-207 and corresponding codes ICD 8-10] registered after the first discharge listing GPA. The GPA diagnosis was evaluated using the European Medical Association classification algorithm. To confirm the hematological malignancy, all diagnostic bone marrow samples were reclassified. Clinical data of both the GPA and hematological malignancy were collected from medical files.

    RESULTS: Twenty-one cases were identified, all of myeloid origin, including 9 with myelodysplastic syndrome developing to acute myeloid leukemia (MDS-AML), 7 AML, 3 MDS, and 2 chronic myeloid leukemia. The median time from GPA diagnosis to hematological malignancy was 8 years (range 5-21). All patients had severe generalized GPA and had received high doses of cyclophosphamide (CYC; median cumulative dose 96.5 g). Cytopenia occurred in 76% of the patients prior to the hematological malignancy.

    CONCLUSION: The findings emphasize the longterm risk of leukemia and MDS in CYC-treated, severely ill patients with GPA. Cytopenia during the course of GPA may be a warning sign and warrants a liberal attitude toward bone marrow examination.

  • 9.
    Segerberg, Filip
    et al.
    Karolinska Inst, Ctr Haematol & Regenerat Med, Dept Med, Stockholm, Sweden.
    Lundtoft, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Reid, Sarah
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Hjorton, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Leonard, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Nordmark, Gunnel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Carlsten, Mattias
    Karolinska Inst, Ctr Haematol & Regenerat Med, Dept Med, Stockholm, Sweden.
    Hagberg, Niklas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala Univ, Dept Med Sci, Rheumatol & Sci Life Labs, Uppsala, Sweden.
    Autoantibodies to Killer Cell Immunoglobulin-Like Receptors in Patients With Systemic Lupus Erythematosus Induce Natural Killer Cell Hyporesponsiveness2019In: Frontiers in Immunology, ISSN 1664-3224, E-ISSN 1664-3224, Vol. 10, article id 2164Article in journal (Refereed)
    Abstract [en]

    Natural killer (NK) cell cytotoxicity toward self-cells is restrained by the inhibitory HLA class I-binding receptors CD94/NKG2A and the killer cell immunoglobulin-like receptors (KIRs). CD94/NKG2A and KIRs are also essential for NK cell education, which is a dynamic functional maturation process where a constitutive binding of inhibitory receptors to cognate HLA class I molecules is required for NK cells to maintain their full cytotoxic capacity. Previously, we described autoantibodies to CD94/NKG2A in patients with systemic lupus erythematosus (SLE). In this study we analyzed sera from 191 patients with SLE, 119 patients with primary Sjogren's syndrome (pSS), 48 patients with systemic sclerosis (SSc), and 100 healthy donors (HD) for autoantibodies to eight different KIRs. Anti-KIR autoantibodies were identified in sera from 23.0% of patients with SLE, 10.9% of patients with pSS, 12.5% of patients with SSc, and 3.0% of HD. IgG from anti-KIR-positive SLE patients reduced the degranulation and cytotoxicity of NK cells toward K562 tumor cells. The presence of anti-KIR-autoantibodies reacting with >3 KIRs was associated with an increased disease activity (p < 0.0001), elevated serum levels of IFN-alpha (p < 0.0001), nephritis (p = 0.001), and the presence of anti-Sm (p = 0.007), and anti-RNP (p = 0.003) autoantibodies in serum. Together these findings suggest that anti-KIR autoantibodies may contribute to the reduced function of NK cells in SLE patients, and that a defective NK cell function may be a risk factor for the development of lupus nephritis.

1 - 9 of 9
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf