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  • 1.
    Carlsson Almlöf, Jonas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Alexsson, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Imgenberg-Kreuz, Juliana
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
    Sylwan, Lina
    Karolinska Inst, Dept Biosci & Nutr, Sci Life Lab SciLifeLab, Solna, Sweden..
    Bäcklin, Christofer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. 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.
    Tandre, Karolina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    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.
    Padyukov, Leonid
    Karolinska Univ Hosp, Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Bengtsson, Christine
    Umea Univ, Dept Publ Hlth & Clin Med Rheumatol, Umea, Sweden..
    Jonsen, Andreas
    Lund Univ, Skane Univ Hosp, Dept Clin Sci, Rheumatol, Lund, Sweden..
    Dahlqvist, Solbritt Rantapaa
    Umea Univ, Dept Publ Hlth & Clin Med Rheumatol, Umea, Sweden..
    Sjowall, Christopher
    Linkoping Univ, Dept Clin & Expt Med, AIR Rheumatol, Linkoping, Sweden..
    Bengtsson, Anders A.
    Lund Univ, Skane Univ Hosp, Dept Clin Sci, Rheumatol, Lund, Sweden..
    Gunnarsson, Iva
    Karolinska Univ Hosp, Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Svenungsson, Elisabet
    Karolinska Univ Hosp, Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    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.
    Sandling, Johanna K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Syvänen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Novel risk genes for systemic lupus erythematosus predicted by random forest classification2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 6236Article in journal (Refereed)
    Abstract [en]

    Genome-wide association studies have identified risk loci for SLE, but a large proportion of the genetic contribution to SLE still remains unexplained. To detect novel risk genes, and to predict an individual's SLE risk we designed a random forest classifier using SNP genotype data generated on the "Immunochip" from 1,160 patients with SLE and 2,711 controls. Using gene importance scores defined by the random forest classifier, we identified 15 potential novel risk genes for SLE. Of them 12 are associated with other autoimmune diseases than SLE, whereas three genes (ZNF804A, CDK1, and MANF) have not previously been associated with autoimmunity. Random forest classification also allowed prediction of patients at risk for lupus nephritis with an area under the curve of 0.94. By allele-specific gene expression analysis we detected cis-regulatory SNPs that affect the expression levels of six of the top 40 genes designed by the random forest analysis, indicating a regulatory role for the identified risk variants. The 40 top genes from the prediction were overrepresented for differential expression in B and T cells according to RNA-sequencing of samples from five healthy donors, with more frequent over-expression in B cells compared to T cells.

  • 2. Grundberg, Ida
    et al.
    Kiflemariam, Sara
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Genomics. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Mignardi, Marco
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Imgenberg-Kreuz, Juliana
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Edlund, Karolina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Micke, Patrick
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Sundström, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Sjöblom, Tobias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Botling, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Nilsson, Mats
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular tools.
    In situ mutation detection and visualization of intratumor heterogeneity for cancer research and diagnostics2013In: Oncotarget, ISSN 1949-2553, Vol. 4, no 12, p. 2407-2418Article in journal (Refereed)
    Abstract [en]

    Current assays for somatic mutation analysis are based on extracts from tissue sections that often contain morphologically heterogeneous neoplastic regions with variable contents of normal stromal and inflammatory cells, obscuring the results of the assays. We have developed an RNA-based in situ mutation assay that targets oncogenic mutations in a multiplex fashion that resolves the heterogeneity of the tissue sample. Activating oncogenic mutations are targets for a new generation of cancer drugs. For anti-EGFR therapy prediction, we demonstrate reliable in situ detection of KRAS mutations in codon 12 and 13 in colon and lung cancers in three different types of routinely processed tissue materials. High-throughput screening of KRAS mutation status was successfully performed on a tissue microarray. Moreover, we show how the patterns of expressed mutated and wild-type alleles can be studied in situ in tumors with complex combinations of mutated EGFR, KRAS and TP53. This in situ method holds great promise as a tool to investigate the role of somatic mutations during tumor progression and for prediction of response to targeted therapy.

  • 3.
    Imgenberg-Kreuz, Juliana
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
    Epigenetic and Gene Expression Signatures in Systemic Inflammatory Autoimmune Diseases2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Autoimmune diseases are clinical manifestations of a loss-of-tolerance of the immune system against the body’s own substances and healthy tissues. Primary Sjögren’s syndrome (pSS) and systemic lupus erythematosus (SLE) are two chronic inflammatory autoimmune diseases characterized by autoantibody production and an activated type I interferon system. Although the precise mechanisms leading to autoimmune processes are not well defined, recent studies suggest that aberrant DNA methylation and gene expression patterns may play a central role in the pathogenesis of these disorders. The aim of this thesis was to investigate DNA methylation and gene expression in pSS and SLE on a genome-wide scale to advance our understanding of how these factors contribute to the diseases and to identify potential biomarkers and novel treatment targets.

    In study I, differential DNA methylation was analyzed in multiple tissues from pSS patients and healthy controls. We identified thousands of CpG sites with perturbed methylation; the most prominent finding was a profound hypomethylation at regulatory regions of type I interferon induced genes in pSS. In study II, a cases-case study comparing DNA methylation in pSS patients with high fatigue to patients with low fatigue, we found methylation patterns associated to the degree of fatigue. In study III, RNA-sequencing was applied to investigate the transcriptome of B cells in pSS in comparison to controls. Increased expression of type I and type II interferon regulated genes in pSS was observed, indicating ongoing immune activation in B cells. In study IV, the impact of DNA methylation on disease susceptibility and phenotypic variability in SLE was investigated. We identified DNA methylation patterns associated to disease susceptibility, SLE manifestations and different treatments. In addition, we mapped methylation quantitative trait loci and observed evidence for genetic regulation of DNA methylation in SLE.  

    In conclusion, the results presented in this thesis provide new insights into the molecular mechanisms underlying autoimmunity in pSS and SLE. The studies confirm the central role of the interferon system in pSS and SLE and further suggest novel genes and mechanisms to be involved in the pathogenesis these autoimmune diseases.

    List of papers
    1. Genome-wide DNA methylation analysis in multiple tissues in primary Sjögren's syndrome reveals regulatory effects at interferon-induced genes
    Open this publication in new window or tab >>Genome-wide DNA methylation analysis in multiple tissues in primary Sjögren's syndrome reveals regulatory effects at interferon-induced genes
    Show others...
    2016 (English)In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 75, no 11, p. 2029-2036Article in journal (Refereed) Published
    Abstract [en]

    OBJECTIVES: Increasing evidence suggests an epigenetic contribution to the pathogenesis of autoimmune diseases, including primary Sjögren's Syndrome (pSS). The aim of this study was to investigate the role of DNA methylation in pSS by analysing multiple tissues from patients and controls.

    METHODS: Genome-wide DNA methylation profiles were generated using HumanMethylation450K BeadChips for whole blood, CD19+ B cells and minor salivary gland biopsies. Gene expression was analysed in CD19+ B cells by RNA-sequencing. Analysis of genetic regulatory effects on DNA methylation at known pSS risk loci was performed.

    RESULTS: We identified prominent hypomethylation of interferon (IFN)-regulated genes in whole blood and CD19+ B cells, including at the genes MX1, IFI44L and PARP9, replicating previous reports in pSS, as well as identifying a large number of novel associations. Enrichment for genomic overlap with histone marks for enhancer and promoter regions was observed. We showed for the first time that hypomethylation of IFN-regulated genes in pSS B cells was associated with their increased expression. In minor salivary gland biopsies we observed hypomethylation of the IFN-induced gene OAS2. Pathway and disease analysis resulted in enrichment of antigen presentation, IFN signalling and lymphoproliferative disorders. Evidence for genetic control of methylation levels at known pSS risk loci was observed.

    CONCLUSIONS: Our study highlights the role of epigenetic regulation of IFN-induced genes in pSS where replication is needed for novel findings. The association with altered gene expression suggests a functional mechanism for differentially methylated CpG sites in pSS aetiology.

    National Category
    Rheumatology and Autoimmunity
    Identifiers
    urn:nbn:se:uu:diva-278026 (URN)10.1136/annrheumdis-2015-208659 (DOI)000386469300023 ()26857698 (PubMedID)
    Funder
    Knut and Alice Wallenberg FoundationSwedish Society for Medical Research (SSMF), 521-2014-2263 521-2013-2830Swedish Research Council, 350-2012-256Science for Life Laboratory - a national resource center for high-throughput molecular bioscience
    Note

    De 2 första författarna delar förstaförfattarskapet.

    Available from: 2016-02-23 Created: 2016-02-23 Last updated: 2017-11-30Bibliographically approved
    2. Epigenome-wide DNA methylation patterns associated with fatigue in primary Sjogren's syndrome
    Open this publication in new window or tab >>Epigenome-wide DNA methylation patterns associated with fatigue in primary Sjogren's syndrome
    Show others...
    2016 (English)In: Rheumatology, ISSN 1462-0324, E-ISSN 1462-0332, Vol. 55, no 6, p. 1074-1082Article in journal (Refereed) Published
    Abstract [en]

    Objective. Chronic fatigue is a common, disabling and poorly understood phenomenon. Recent studies indicate that epigenetic mechanisms may be involved in the expression of fatigue, a prominent feature of primary SS (pSS). The aim of this study was to investigate whether DNA methylation profiles of whole blood are associated with fatigue in patients with pSS. Methods. Forty-eight pSS patients with high (n = 24) or low (n = 24) fatigue as measured by a visual analogue scale were included. Genome-wide DNA methylation was investigated using the Illumina HumanMethylation450 BeadChip array. After quality control, a total of 383 358 Cytosine-phosphate-Guanine (CpG) sites remained for further analysis. Age, sex and differential cell count estimates were included as covariates in the association model. A false discovery rate-corrected P < 0.05 was considered significant, and a cut-off of 3% average difference in methylation levels between high- and low-fatigue patients was applied. Results. A total of 251 differentially methylated CpG sites were associated with fatigue. The CpG site with the most pronounced hypomethylation in pSS high fatigue annotated to the SBF2-antisense RNA1 gene. The most distinct hypermethylation was observed at a CpG site annotated to the lymphotoxin alpha gene. Functional pathway analysis of genes with differently methylated CpG sites in subjects with high vs low fatigue revealed enrichment in several pathways associated with innate and adaptive immunity. Conclusion. Some genes involved in regulation of the immune system and in inflammation are differently methylated in pSS patients with high vs low fatigue. These findings point to functional networks that may underlie fatigue. Epigenetic changes could constitute a fatigue-regulating mechanism in pSS.

    Keywords
    primary Sjogren's syndrome, epigenetics, DNA methylation, fatigue
    National Category
    Rheumatology and Autoimmunity
    Identifiers
    urn:nbn:se:uu:diva-299502 (URN)10.1093/rheumatology/kew008 (DOI)000377432200015 ()
    Available from: 2016-07-22 Created: 2016-07-22 Last updated: 2017-11-28Bibliographically approved
    3. Transcription profiling in CD19+ B-cells in primary Sjögren's syndrome reveals an interferon-signature with upregulated BAFF and TLR7
    Open this publication in new window or tab >>Transcription profiling in CD19+ B-cells in primary Sjögren's syndrome reveals an interferon-signature with upregulated BAFF and TLR7
    Show others...
    (English)Manuscript (preprint) (Other academic)
    National Category
    Medical and Health Sciences
    Research subject
    Medical Science
    Identifiers
    urn:nbn:se:uu:diva-310386 (URN)
    Available from: 2016-12-14 Created: 2016-12-14 Last updated: 2016-12-14
    4. DNA methylation mapping identifies gene regulatory effects in patients with systemic lupus erythematosus (SLE)
    Open this publication in new window or tab >>DNA methylation mapping identifies gene regulatory effects in patients with systemic lupus erythematosus (SLE)
    Show others...
    (English)Manuscript (preprint) (Other academic)
    National Category
    Medical and Health Sciences
    Research subject
    Medical Science
    Identifiers
    urn:nbn:se:uu:diva-310387 (URN)
    Available from: 2016-12-14 Created: 2016-12-14 Last updated: 2016-12-14
  • 4.
    Imgenberg-Kreuz, Juliana
    et al.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Almlöf, Jonas Carlsson
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. 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.
    Alexsson, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Nordmark, Gunnel
    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.
    Rantapää-Dahlqvist, Solbritt
    Umeå University, Umeå, Sweden.
    Bengtsson, Anders A
    Lund University, Skane University Hospital, Lund, Sweden.
    Jönsen, Andreas
    Lund University, Skane University Hospital, Lund, Sweden.
    Padyukov, Leonid
    Karolinska University Hospital, Stockholm, Sweden.
    Gunnarsson, Iva
    Karolinska University Hospital, Stockholm, Sweden.
    Svenungsson, Elisabet
    Karolinska University Hospital, Stockholm, Sweden.
    Sjöwall, Christopher
    Linköping University, Linköping, Sweden.
    Rönnblom, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Syvänen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. 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, Molecular Medicine. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    DNA methylation mapping identifies gene regulatory effects in patients with systemic lupus erythematosus2018In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 77, no 5, p. 736-743Article in journal (Refereed)
    Abstract [en]

    Objectives: Systemic lupus erythematosus (SLE) is a chronic autoimmune condition with heterogeneous presentation and complex aetiology where DNA methylation changes are emerging as a contributing factor. In order to discover novel epigenetic associations and investigate their relationship to genetic risk for SLE, we analysed DNA methylation profiles in a large collection of patients with SLE and healthy individuals.

    Methods: DNA extracted from blood from 548 patients with SLE and 587 healthy controls were analysed on the Illumina HumanMethylation 450 k BeadChip, which targets 485 000 CpG sites across the genome. Single nucleotide polymorphism (SNP) genotype data for 196 524 SNPs on the Illumina ImmunoChip from the same individuals were utilised for methylation quantitative trait loci (cis-meQTLs) analyses.

    Results: We identified and replicated differentially methylated CpGs (DMCs) in SLE at 7245 CpG sites in the genome. The largest methylation differences were observed at type I interferon-regulated genes which exhibited decreased methylation in SLE. We mapped cis-meQTLs and identified genetic regulation of methylation levels at 466 of the DMCs in SLE. The meQTLs for DMCs in SLE were enriched for genetic association to SLE, and included seven SLE genome-wide association study (GWAS) loci: PTPRC (CD45), MHC-class III, UHRF1BP1, IRF5, IRF7, IKZF3 and UBE2L3. In addition, we observed association between genotype and variance of methylation at 20 DMCs in SLE, including at the HLA-DQB2 locus.

    Conclusions: Our results suggest that several of the genetic risk variants for SLE may exert their influence on the phenotype through alteration of DNA methylation levels at regulatory regions of target genes.

  • 5.
    Imgenberg-Kreuz, Juliana
    et al.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Almlöf, Jonas Carlsson
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. 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.
    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.
    Padyukov, Leonid
    Karolinska Univ Hosp, Karolinska Inst, Rheumatol Unit, Dept Med Solna, Stockholm, Sweden..
    Gunnarsson, Iva
    Karolinska Univ Hosp, Karolinska Inst, Rheumatol Unit, Dept Med Solna, Stockholm, Sweden..
    Svenungsson, Elisabet
    Karolinska Univ Hosp, Karolinska Inst, Rheumatol Unit, Dept Med Solna, Stockholm, Sweden..
    Sjowall, Christopher
    Linkoping Univ, Rheumatol AIR, Dept Clin & Expt Med, Linkoping, Sweden..
    Rönnblom, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Syvänen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. 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, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Treatment-Associated DNA Methylation Patterns in Systemic Lupus Erythematosus2017In: Arthritis & Rheumatology, ISSN 2326-5191, E-ISSN 2326-5205, Vol. 69, no S10, article id 2654Article in journal (Other academic)
  • 6.
    Imgenberg-Kreuz, Juliana
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. 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, Molecular Medicine. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Almlöf, Jonas Carlsson
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Nordlund, Jessica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Signer, Linnea
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Norheim, Katrine B.
    Stavanger Univ Hosp, Dept Internal Med, Clin Immunol Unit, Stavanger, Norway..
    Omdal, Roald
    Stavanger Univ Hosp, Dept Internal Med, Clin Immunol Unit, Stavanger, Norway..
    Eloranta, Majia-Leena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    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.
    Syvanen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. 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.
    Hypomethylation in Enhancer and Promoter Regions of Interferon Regulated Genes in Multiple Tissues Is Associated with Primary Sjogren's Syndrome2015In: Arthritis & Rheumatology, ISSN 2326-5191, E-ISSN 2326-5205, Vol. 67, no Suppl. 10, article id 2100Article in journal (Other academic)
  • 7.
    Imgenberg-Kreuz, Juliana
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. 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, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Almlöf, Jonas Carlsson
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Nordlund, Jessica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Signér, Linnea
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Norheim, Katrine Braekke
    Stavanger Univ Hosp, Dept Internal Med, Clin Immunol Unit, Stavanger, Norway.
    Omdal, Roald
    Stavanger Univ Hosp, Dept Internal Med, Clin Immunol Unit, Stavanger, Norway.
    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.
    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.
    Syvänen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. 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.
    Genome-wide DNA methylation analysis in multiple tissues in primary Sjögren's syndrome reveals regulatory effects at interferon-induced genes2016In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 75, no 11, p. 2029-2036Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Increasing evidence suggests an epigenetic contribution to the pathogenesis of autoimmune diseases, including primary Sjögren's Syndrome (pSS). The aim of this study was to investigate the role of DNA methylation in pSS by analysing multiple tissues from patients and controls.

    METHODS: Genome-wide DNA methylation profiles were generated using HumanMethylation450K BeadChips for whole blood, CD19+ B cells and minor salivary gland biopsies. Gene expression was analysed in CD19+ B cells by RNA-sequencing. Analysis of genetic regulatory effects on DNA methylation at known pSS risk loci was performed.

    RESULTS: We identified prominent hypomethylation of interferon (IFN)-regulated genes in whole blood and CD19+ B cells, including at the genes MX1, IFI44L and PARP9, replicating previous reports in pSS, as well as identifying a large number of novel associations. Enrichment for genomic overlap with histone marks for enhancer and promoter regions was observed. We showed for the first time that hypomethylation of IFN-regulated genes in pSS B cells was associated with their increased expression. In minor salivary gland biopsies we observed hypomethylation of the IFN-induced gene OAS2. Pathway and disease analysis resulted in enrichment of antigen presentation, IFN signalling and lymphoproliferative disorders. Evidence for genetic control of methylation levels at known pSS risk loci was observed.

    CONCLUSIONS: Our study highlights the role of epigenetic regulation of IFN-induced genes in pSS where replication is needed for novel findings. The association with altered gene expression suggests a functional mechanism for differentially methylated CpG sites in pSS aetiology.

  • 8.
    Imgenberg-Kreuz, Juliana
    et al.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Sandling, Johanna K.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Bjork, A.
    Karolinska Inst, Dept Med, Karolinska Univ Hosp, Stockholm, Sweden.
    Nordlund, J.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Kvarnstrom, M.
    Karolinska Inst, Dept Med, Karolinska Univ Hosp, Stockholm, 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.
    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.
    Wahren-Herlenius, M.
    Karolinska Inst, Dept Med, Karolinska Univ Hosp, Stockholm, Sweden.
    Syvänen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. 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.
    Transcription profiling of peripheral B cells in antibody-positive primary Sjogren's syndrome reveals upregulated expression of CX3CR1 and a type I and type II interferon signature2018In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 87, no 5, article id UNSP e12662Article in journal (Refereed)
    Abstract [en]

    B cells play a key role in the pathogenesis of primary Sjogren's syndrome (pSS). The aim of this study was to analyse the transcriptome of CD19+ B cells from patients with pSS and healthy controls to decipher the B cell-specific contribution to pSS. RNA from purified CD19+ B cells from 12 anti-SSA antibody-positive untreated female patients with pSS and 20 healthy blood donors was subjected to whole transcriptome sequencing. A false discovery rate corrected significance threshold of <0.05 was applied to define differential gene expression. As validation, gene expression in B cells from 17 patients with pSS and 16 healthy controls was analysed using a targeted gene panel. RNA-sequencing identified 4047 differentially expressed autosomal genes in pSS B cells. Upregulated expression of type I and type II interferon (IFN)-induced genes was observed, establishing an IFN signature in pSS B cells. Among the top upregulated and validated genes were CX3CR1, encoding the fractalkine receptor involved in regulation of B-cell malignancies, CCL5/RANTES and CCR1. Increased expression of several members of the TNF superfamily was also identified; TNFSF4/Ox40L, TNFSF10/TRAIL, TNFSF13B/BAFF, TNFRSF17/BCMA as well as S100A8 and -A9/calprotectin, TLR7, STAT1 and STAT2. Among genes with downregulated expression in pSS B cells were SOCS1 and SOCS3, CD70 and TNFAIP3/A20. We conclude that B cells from patients with anti-SSA antibody-positive pSS display immune activation with upregulated expression of chemokines, chemokine receptors and a prominent type I and type II IFN signature, while suppressors of cytokine signalling are downregulated. This adds insight into the autoimmune process and suggests potential targets for future functional studies.

  • 9.
    Imgenberg-Kreuz, Juliana
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. 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.
    Carlsson Almlöf, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Omdal, Roald
    Norheim, Katrine Braekke
    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.
    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.
    Syvänen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics. 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.
    Genome-Wide Analysis of DNA Methylation Profiles in Multiple Tissues in Primary Sjogren's Syndrome2015In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 81, no 5, p. 412-412Article in journal (Other academic)
  • 10.
    Nordmark, Gunnel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Imgenberg-Kreuz, Juliana
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
    Almlöf, Jonas Carlsson
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
    Nordlund, Jessica
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
    Omdal, Roald
    Norheim, Katrine B.
    Eloranta, Maija-Leena
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Rönnblom, Lars
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Sandling, Johanna K.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
    Genome-Wide DNA Methylation Analysis of CD19+B Cells in Primary Sjogren's Syndrome2014In: Arthritis & Rheumatology, ISSN 2326-5191, Vol. 66, no S10, p. S1303-S1303, article id 2980Article in journal (Other academic)
  • 11.
    Norheim, Katrine
    et al.
    Stavanger Univ Hosp, Clin Immunol Dept, Stavanger, Norway..
    Alexsson, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Imgenberg-Kreuz, Juliana
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Brun, Johan Gorgas
    Haukeland Hosp, Rheumatol Sect, Bergen, Norway.;Univ Bergen, Dept Clin Sci, Bergen, Norway..
    Jonsson, Roland
    Univ Bergen, Dept Clin Sci, Broegelmann Res Lab, Bergen, Norway..
    Ng, Wan-Fai
    Newcastle Upon Tyne Hosp NHS Fdn Trust, Newcastle Upon Tyne, Tyne & Wear, England.;Newcastle Univ, Inst Cellular Med, Musculoskeletal Res Grp, Newcastle Upon Tyne, Tyne & Wear, England..
    Theander, Elke
    Lund Univ, Skane Univ Hosp Malmo, Dept Rheumatol, Malmo, Sweden..
    Mandl, Thomas
    Skane Univ Hosp, Dept Rheumatol, Malmo, Sweden..
    Sivils, Kathy L.
    Oklahoma Med Res Fdn, Arthrit & Clin Immunol Program, 825 NE 13th St, Oklahoma City, OK 73104 USA..
    Rönnblom, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Nordmark, Gunnel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Omdal, Roald
    Univ Bergen, Dept Clin Sci, Bergen, Norway.;Stavanger Univ Hosp, Dept Internal Med, Clin Immunol Unit, Stavanger, Norway..
    Genetic Determinants of Fatigue in Primary Sjogren's Syndrome: a Genome Wide Association Study2017In: Arthritis & Rheumatology, ISSN 2326-5191, E-ISSN 2326-5205, Vol. 69, no S10, article id 182Article in journal (Other academic)
  • 12.
    Norheim, Katrine B.
    et al.
    Dept Internal Med, Clin Immunol Unit, Stavanger, Norway..
    Imgenberg-Kreuz, Juliana
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Jonsdottir, Kristin
    Stavanger Univ Hosp, Dept Pathol, Stavanger, Norway..
    Janssen, Emiel
    Stavanger Univ Hosp, Dept Pathol, Stavanger, Norway..
    Syvänen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. 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, Molecular Medicine. 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.
    Omdal, Roald
    Dept Internal Med, Clin Immunol Unit, Stavanger, Norway..
    Epigenome-Wide DNA Methylation Patterns Associated with Fatigue in Primary Sjogren's Syndrome2015In: Arthritis & Rheumatology, ISSN 2326-5191, E-ISSN 2326-5205, Vol. 67, no Suppl. 10, article id 1262Article in journal (Other academic)
  • 13.
    Norheim, Katrine Braekke
    et al.
    Stavanger Univ Hosp, Clin Immunol Unit, Dept Internal Med, Pb 8100 Forus, N-4068 Stavanger, Norway..
    Imgenberg-Kreuz, Juliana
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
    Jonsdottir, Kristin
    Stavanger Univ Hosp, Dept Pathol, N-4068 Stavanger, Norway..
    Janssen, Emiel A. M.
    Stavanger Univ Hosp, Dept Pathol, N-4068 Stavanger, Norway..
    Syvänen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
    Sandling, Johanna K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Nordmark, Gunnel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Omdal, Roald
    Stavanger Univ Hosp, Clin Immunol Unit, Dept Internal Med, Pb 8100 Forus, N-4068 Stavanger, Norway..
    Epigenome-wide DNA methylation patterns associated with fatigue in primary Sjogren's syndrome2016In: Rheumatology, ISSN 1462-0324, E-ISSN 1462-0332, Vol. 55, no 6, p. 1074-1082Article in journal (Refereed)
    Abstract [en]

    Objective. Chronic fatigue is a common, disabling and poorly understood phenomenon. Recent studies indicate that epigenetic mechanisms may be involved in the expression of fatigue, a prominent feature of primary SS (pSS). The aim of this study was to investigate whether DNA methylation profiles of whole blood are associated with fatigue in patients with pSS. Methods. Forty-eight pSS patients with high (n = 24) or low (n = 24) fatigue as measured by a visual analogue scale were included. Genome-wide DNA methylation was investigated using the Illumina HumanMethylation450 BeadChip array. After quality control, a total of 383 358 Cytosine-phosphate-Guanine (CpG) sites remained for further analysis. Age, sex and differential cell count estimates were included as covariates in the association model. A false discovery rate-corrected P < 0.05 was considered significant, and a cut-off of 3% average difference in methylation levels between high- and low-fatigue patients was applied. Results. A total of 251 differentially methylated CpG sites were associated with fatigue. The CpG site with the most pronounced hypomethylation in pSS high fatigue annotated to the SBF2-antisense RNA1 gene. The most distinct hypermethylation was observed at a CpG site annotated to the lymphotoxin alpha gene. Functional pathway analysis of genes with differently methylated CpG sites in subjects with high vs low fatigue revealed enrichment in several pathways associated with innate and adaptive immunity. Conclusion. Some genes involved in regulation of the immune system and in inflammation are differently methylated in pSS patients with high vs low fatigue. These findings point to functional networks that may underlie fatigue. Epigenetic changes could constitute a fatigue-regulating mechanism in pSS.

  • 14. Norheim, Katrine Braekke
    et al.
    Imgenberg-Kreuz, Juliana
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Jonsdottir, Kristin
    Sandling, Johanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Syvanen, Ann-Christine
    Nordmark, Gunnel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Omdal, Roald
    Genome-Wide DNA Methylation Patterns Associated with Fatigue in Primary Sjogren's Syndrome2015In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 81, no 5, p. 413-413Article in journal (Other academic)
  • 15.
    Sandling, Johanna K.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Imgenberg-Kreuz, Juliana
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
    Carlsson Almlöf, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. 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.
    Eloranta, Maija-Leena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Padyukov, L.
    Karolinska Inst, Karolinska Univ Hosp, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Gunnarsson, I.
    Karolinska Inst, Karolinska Univ Hosp, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Svenungsson, E.
    Karolinska Inst, Karolinska Univ Hosp, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Sjowall, C.
    Linkoping Univ, Dept Clin & Expt Med, Rheumatol AIR, Linkoping, Sweden..
    Rönnblom, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Syvänen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Genome-wide analysis of DNA methylation in systemic lupus erythematosus2015In: Clinical and Experimental Rheumatology, ISSN 0392-856X, E-ISSN 1593-098X, Vol. 33, no 3, p. S74-S74Article in journal (Other academic)
1 - 15 of 15
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