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Aqrawi, L. A., Ivanchenko, M., Björk, A., Ramírez Sepúlveda, J. I., Imgenberg-Kreuz, J., Kvarnström, M., . . . Wahren-Herlenius, M. (2018). Diminished CXCR5 expression in peripheral blood of patients with Sjögren's syndrome may relate to both genotype and salivary gland homing. Clinical and Experimental Immunology, 192(3), 259-270
Open this publication in new window or tab >>Diminished CXCR5 expression in peripheral blood of patients with Sjögren's syndrome may relate to both genotype and salivary gland homing
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2018 (English)In: Clinical and Experimental Immunology, ISSN 0009-9104, E-ISSN 1365-2249, Vol. 192, no 3, p. 259-270Article in journal (Refereed) Published
Abstract [en]

cells in circulation was also related to homing of B and T cells to the autoimmune target organ. Therapeutic drugs targeting the CXCR5/CXCL13 axis may be useful in SS. This article is protected by copyright. All rights reserved.

Place, publisher, year, edition, pages
John Wiley & Sons, 2018
Keywords
B cells, CXCR5, Sjögren's syndrome, T cells, eQTL
National Category
Rheumatology and Autoimmunity
Identifiers
urn:nbn:se:uu:diva-343237 (URN)10.1111/cei.13118 (DOI)000434078000002 ()29453859 (PubMedID)
Funder
Swedish Research CouncilSwedish Rheumatism AssociationKing Gustaf V Jubilee FundEU, FP7, Seventh Framework Programme, 608695Stockholm County Council
Available from: 2018-02-26 Created: 2018-02-26 Last updated: 2018-09-28Bibliographically approved
Imgenberg-Kreuz, J., Almlöf, J. C., Leonard, D., Alexsson, A., Nordmark, G., Eloranta, M.-L., . . . Sandling, J. K. (2018). DNA methylation mapping identifies gene regulatory effects in patients with systemic lupus erythematosus. Annals of the Rheumatic Diseases, 77(5), 736-743
Open this publication in new window or tab >>DNA methylation mapping identifies gene regulatory effects in patients with systemic lupus erythematosus
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2018 (English)In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 77, no 5, p. 736-743Article in journal (Refereed) Published
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.

Keywords
gene polymorphism, systemic lupus erythematosus
National Category
Rheumatology and Autoimmunity
Identifiers
urn:nbn:se:uu:diva-342164 (URN)10.1136/annrheumdis-2017-212379 (DOI)000430492600020 ()29437559 (PubMedID)
Funder
Knut and Alice Wallenberg Foundation, KAW 2011.0073Swedish Research Council, 521-2014-2263; 521-2013-2830; 521-2014-3954; 2016-01982; 350-2012-256AstraZenecaSwedish Society for Medical Research (SSMF)Swedish Rheumatism AssociationThe King Gustaf V's Jubilee FoundationSwedish Heart Lung FoundationStockholm County CouncilScience for Life Laboratory - a national resource center for high-throughput molecular bioscience
Available from: 2018-02-19 Created: 2018-02-19 Last updated: 2018-06-19Bibliographically approved
Bremer, H. D., Landegren, N., Sjöberg, R., Hallgren, Å., Renneker, S., Lattwein, E., . . . Hansson-Hamlin, H. (2018). ILF2 and ILF3 are autoantigens in canine systemic autoimmune disease. Scientific Reports, 8, Article ID 4852.
Open this publication in new window or tab >>ILF2 and ILF3 are autoantigens in canine systemic autoimmune disease
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2018 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 4852Article in journal (Refereed) Published
Abstract [en]

Dogs can spontaneously develop complex systemic autoimmune disorders, with similarities to human autoimmune disease. Autoantibodies directed at self-antigens are a key feature of these autoimmune diseases. Here we report the identification of interleukin enhancer-binding factors 2 and 3 (ILF2 and ILF3) as autoantigens in canine immune-mediated rheumatic disease. The ILF2 autoantibodies were discovered in a small, selected canine cohort through the use of human protein arrays; a method not previously described in dogs. Subsequently, ILF3 autoantibodies were also identified in the same cohort. The results were validated with an independent method in a larger cohort of dogs. ILF2 and ILF3 autoantibodies were found exclusively, and at a high frequency, in dogs that showed a speckled pattern of antinuclear antibodies on immunofluorescence. ILF2 and ILF3 autoantibodies were also found at low frequency in human patients with SLE and Sjogren's syndrome. These autoantibodies have the potential to be used as diagnostic biomarkers for canine, and possibly also human, autoimmune disease.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP, 2018
National Category
Immunology in the medical area
Identifiers
urn:nbn:se:uu:diva-351425 (URN)10.1038/s41598-018-23034-w (DOI)000427688100045 ()29556082 (PubMedID)
Funder
Swedish Research CouncilSwedish Research Council Formas, 2011-1404Novo NordiskRagnar Söderbergs stiftelseSwedish Rheumatism Association
Available from: 2018-06-01 Created: 2018-06-01 Last updated: 2018-06-01Bibliographically approved
Imgenberg-Kreuz, J., Leonard, D., Carlsson Almlöf, J., Rantapaa-Dahlqvist, S., Bengtsson, A., Jonsen, A., . . . Sandling, J. K. (2018). Shared and unique patterns of DNA methylation in primary Sjogren's syndrome and systemic lupus erythematosus. Scandinavian Journal of Rheumatology, 47, 3-3
Open this publication in new window or tab >>Shared and unique patterns of DNA methylation in primary Sjogren's syndrome and systemic lupus erythematosus
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2018 (English)In: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 47, p. 3-3Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
TAYLOR & FRANCIS LTD, 2018
National Category
Rheumatology and Autoimmunity
Identifiers
urn:nbn:se:uu:diva-363887 (URN)000442295400005 ()
Available from: 2018-11-12 Created: 2018-11-12 Last updated: 2018-11-12Bibliographically approved
Imgenberg-Kreuz, J., Sandling, J. K., Bjork, A., Nordlund, J., Kvarnstrom, M., Eloranta, M.-L., . . . Nordmark, G. (2018). 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 signature. Scandinavian Journal of Immunology, 87(5), Article ID UNSP e12662.
Open this publication in new window or tab >>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 signature
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2018 (English)In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 87, no 5, article id UNSP e12662Article in journal (Refereed) Published
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.

National Category
Immunology in the medical area Rheumatology and Autoimmunity
Identifiers
urn:nbn:se:uu:diva-354096 (URN)10.1111/sji.12662 (DOI)000430398400006 ()29655283 (PubMedID)
Funder
Knut and Alice Wallenberg Foundation, 2011.0073Swedish Research Council, 2012-2148Swedish Research Council, 350-2012-256Swedish Research Council, 521-2013-2830Swedish Research Council, 521-2014-2263Swedish Research Council, 2016-01982Knut and Alice Wallenberg FoundationSwedish Research Council
Available from: 2018-06-19 Created: 2018-06-19 Last updated: 2018-06-19Bibliographically approved
Brito-Zeron, P., Acar-Denizli, N., Zeher, M., Rasmussen, A., Seror, R., Mandl, T., . . . Ramos-Casals, M. (2017). Analysis Of 9302 Patients From The Big Data International Primary Sjogren Syndrome Cohort: Clinical Presentation At Diagnosis Of European Vs Non-European Patients. Paper presented at Annual European Congress of Rheumatology, JUN 14-17, 2017, Madrid, SPAIN. Annals of the Rheumatic Diseases, 76, 886-887
Open this publication in new window or tab >>Analysis Of 9302 Patients From The Big Data International Primary Sjogren Syndrome Cohort: Clinical Presentation At Diagnosis Of European Vs Non-European Patients
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2017 (English)In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 76, p. 886-887Article in journal, Meeting abstract (Other academic) Published
National Category
Rheumatology and Autoimmunity
Identifiers
urn:nbn:se:uu:diva-346634 (URN)10.1136/annrheumdis-2017-eular.3502 (DOI)000413181402588 ()
Conference
Annual European Congress of Rheumatology, JUN 14-17, 2017, Madrid, SPAIN
Available from: 2018-03-21 Created: 2018-03-21 Last updated: 2018-04-18Bibliographically approved
Brito-Zeron, P., Acar-Denizli, N., Zeher, M., Rasmussen, A., Li, X., Baldini, C., . . . Ramos-Casals, M. (2017). Baseline Essdai/ Das Scores In 8061 Patients With Primary Sjögren Syndrome: Characterization Of Systemic Disease. Paper presented at Annual European Congress of Rheumatology, JUN 14-17, 2017, Madrid, SPAIN. Annals of the Rheumatic Diseases, 76, 464-465
Open this publication in new window or tab >>Baseline Essdai/ Das Scores In 8061 Patients With Primary Sjögren Syndrome: Characterization Of Systemic Disease
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2017 (English)In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 76, p. 464-465Article in journal, Meeting abstract (Other academic) Published
National Category
Rheumatology and Autoimmunity
Identifiers
urn:nbn:se:uu:diva-346629 (URN)10.1136/annrheumdis-2017-eular.4472 (DOI)000413181401363 ()
Conference
Annual European Congress of Rheumatology, JUN 14-17, 2017, Madrid, SPAIN
Available from: 2018-03-21 Created: 2018-03-21 Last updated: 2018-03-21Bibliographically approved
Ramirez, J., Kvarnstrom, M., Brauner, S., Baldini, C., Eriksson, P., Mandl, T., . . . Wahren-Herlenius, M. (2017). Difference in Clinical Presentation between Female and Male Patients with Primary Sjogren's Syndrome at Diagnosis and in Long-Term Follow-up. Arthritis & Rheumatology, 69(S10), Article ID 1479.
Open this publication in new window or tab >>Difference in Clinical Presentation between Female and Male Patients with Primary Sjogren's Syndrome at Diagnosis and in Long-Term Follow-up
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2017 (English)In: Arthritis & Rheumatology, ISSN 2326-5191, E-ISSN 2326-5205, Vol. 69, no S10, article id 1479Article in journal, Meeting abstract (Other academic) Published
National Category
Rheumatology and Autoimmunity
Identifiers
urn:nbn:se:uu:diva-346797 (URN)000411824103003 ()
Available from: 2018-03-22 Created: 2018-03-22 Last updated: 2018-03-22Bibliographically approved
Retamozo, S., Brito-Zeron, P., Zeher, M., Sivils, K. L., Seror, R., Mandl, T., . . . Ramos-Casals, M. (2017). Epidemiologic Subsets Drive a Differentiated Clinical and Immunological Presentation of Primary Sjogren Syndrome: Analysis of 9302 Patients from the Big Data International Sjogren Cohort. Arthritis & Rheumatology, 69(S10), Article ID 876.
Open this publication in new window or tab >>Epidemiologic Subsets Drive a Differentiated Clinical and Immunological Presentation of Primary Sjogren Syndrome: Analysis of 9302 Patients from the Big Data International Sjogren Cohort
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2017 (English)In: Arthritis & Rheumatology, ISSN 2326-5191, E-ISSN 2326-5205, Vol. 69, no S10, article id 876Article in journal, Meeting abstract (Other academic) Published
National Category
Rheumatology and Autoimmunity
Identifiers
urn:nbn:se:uu:diva-346799 (URN)000411824101159 ()
Available from: 2018-03-22 Created: 2018-03-22 Last updated: 2018-03-22Bibliographically approved
Knight, A., Pauksen, K., Nordmark, G. & Eva, K. (2017). Fatal outcome of tick-borne encephalitis in two patients with rheumatic disease treated with rituximab.. Rheumatology, 56(5), 855-856
Open this publication in new window or tab >>Fatal outcome of tick-borne encephalitis in two patients with rheumatic disease treated with rituximab.
2017 (English)In: Rheumatology, ISSN 1462-0324, E-ISSN 1462-0332, Vol. 56, no 5, p. 855-856Article in journal (Refereed) Published
National Category
Rheumatology and Autoimmunity
Research subject
Medical Science
Identifiers
urn:nbn:se:uu:diva-318795 (URN)10.1093/rheumatology/kew495 (DOI)28130421 (PubMedID)
Available from: 2017-03-28 Created: 2017-03-28 Last updated: 2017-12-07Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-3829-7431

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