uu.seUppsala University Publications
Change search
Link to record
Permanent link

Direct link
BETA
Publications (10 of 15) Show all publications
Landegren, N., Rosen, L. B., Freyhult, E., Eriksson, D., Fall, T., Smith, G., . . . Kampe, O. (2019). Comment on 'AIRE-deficient patients harbor unique high-affinity disease-ameliorating autoantibodies'. eLIFE, 8, Article ID e43578.
Open this publication in new window or tab >>Comment on 'AIRE-deficient patients harbor unique high-affinity disease-ameliorating autoantibodies'
Show others...
2019 (English)In: eLIFE, E-ISSN 2050-084X, Vol. 8, article id e43578Article in journal, Editorial material (Other academic) Published
Abstract [en]

The AIRE gene plays a key role in the development of central immune tolerance by promoting thymic presentation of tissue-specific molecules. Patients with AIRE-deficiency develop multiple autoimmune manifestations and display autoantibodies against the affected tissues. In 2016 it was reported that: i) the spectrum of autoantibodies in patients with AIRE-deficiency is much broader than previously appreciated; ii) neutralizing autoantibodies to type I interferons (IFNs) could provide protection against type 1 diabetes in these patients (Meyer et al., 2016). We attempted to replicate these new findings using a similar experimental approach in an independent patient cohort, and found no evidence for either conclusion.

Place, publisher, year, edition, pages
ELIFE SCIENCES PUBLICATIONS LTD, 2019
National Category
Immunology in the medical area
Identifiers
urn:nbn:se:uu:diva-390333 (URN)10.7554/eLife.43578 (DOI)000473150200001 ()31244471 (PubMedID)
Funder
Swedish Research Council FormasSwedish Research CouncilKnut and Alice Wallenberg FoundationNovo NordiskSwedish Society for Medical Research (SSMF)
Available from: 2019-08-09 Created: 2019-08-09 Last updated: 2019-08-09Bibliographically approved
Eriksson, D., Bacchetta, R., Gunnarsson, H. I., Chan, A., Barzaghi, F., Ehl, S., . . . Landegren, N. (2019). The autoimmune targets in IPEX are dominated by gut epithelial proteins [Letter to the editor]. Journal of Allergy and Clinical Immunology, 144(1), 327-330
Open this publication in new window or tab >>The autoimmune targets in IPEX are dominated by gut epithelial proteins
Show others...
2019 (English)In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 144, no 1, p. 327-330Article in journal, Letter (Other academic) Published
Place, publisher, year, edition, pages
MOSBY-ELSEVIER, 2019
National Category
Respiratory Medicine and Allergy Immunology in the medical area
Identifiers
urn:nbn:se:uu:diva-390434 (URN)10.1016/j.jaci.2019.02.031 (DOI)000473432800039 ()31027649 (PubMedID)
Funder
Swedish Research CouncilTorsten Söderbergs stiftelseRagnar Söderbergs stiftelseNovo NordiskThe Crafoord FoundationStockholm County CouncilSwedish Society for Medical Research (SSMF)
Available from: 2019-08-12 Created: 2019-08-12 Last updated: 2019-08-12Bibliographically approved
Eriksson, D., Bianchi, M., Landegren, N., Dalin, F., Skov, J., Hultin-Rosenberg, L., . . . Kampe, O. (2018). Common genetic variation in the autoimmune regulator (AIRE) locus is associated with autoimmune Addison's disease in Sweden. Scientific Reports, 8, Article ID 8395.
Open this publication in new window or tab >>Common genetic variation in the autoimmune regulator (AIRE) locus is associated with autoimmune Addison's disease in Sweden
Show others...
2018 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 8395Article in journal (Refereed) Published
Abstract [en]

Autoimmune Addison's disease (AAD) is the predominating cause of primary adrenal failure. Despite its high heritability, the rarity of disease has long made candidate-gene studies the only feasible methodology for genetic studies. Here we conducted a comprehensive reinvestigation of suggested AAD risk loci and more than 1800 candidate genes with associated regulatory elements in 479 patients with AAD and 2394 controls. Our analysis enabled us to replicate many risk variants, but several other previously suggested risk variants failed confirmation. By exploring the full set of 1800 candidate genes, we further identified common variation in the autoimmune regulator (AIRE) as a novel risk locus associated to sporadic AAD in our study. Our findings not only confirm that multiple loci are associated with disease risk, but also show to what extent the multiple risk loci jointly associate to AAD. In total, risk loci discovered to date only explain about 7% of variance in liability to AAD in our study population.

National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-357556 (URN)10.1038/s41598-018-26842-2 (DOI)000433538800022 ()29849176 (PubMedID)
Funder
Swedish Research CouncilEU, FP7, Seventh Framework Programme, 201167Swedish Research Council FormasKnut and Alice Wallenberg FoundationRagnar Söderbergs stiftelseTorsten Söderbergs stiftelseNovo NordiskMarianne and Marcus Wallenberg FoundationTore Nilsons Stiftelse för medicinsk forskningÅke Wiberg FoundationSwedish Rheumatism AssociationSwedish Society of Medicine
Available from: 2018-08-20 Created: 2018-08-20 Last updated: 2018-08-20Bibliographically approved
Eriksson, D., Dalin, F., Eriksson, G. N., Landegren, N., Bianchi, M., Hallgren, Å., . . . Kämpe, O. (2018). Cytokine Autoantibody Screening in the Swedish Addison Registry Identifies Patients With Undiagnosed APS1. Journal of Clinical Endocrinology and Metabolism, 103(1), 179-186
Open this publication in new window or tab >>Cytokine Autoantibody Screening in the Swedish Addison Registry Identifies Patients With Undiagnosed APS1
Show others...
2018 (English)In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 103, no 1, p. 179-186Article in journal (Refereed) Published
Abstract [en]

Context: Autoimmune polyendocrine syndrome type 1 (APS1) is a monogenic disorder that features autoimmune Addison disease as a major component. Although APS1 accounts for only a small fraction of all patients with Addison disease, early identification of these individuals is vital to prevent the potentially lethal complications of APS1.

Objective: To determine whether available serological and genetic markers are valuable screening tools for the identification of APS1 among patients diagnosed with Addison disease.

Design: We systematically screened 677 patients with Addison disease enrolled in the Swedish Addison Registry for autoantibodies against interleukin-22 and interferon-α4. Autoantibody-positive patients were investigated for clinical manifestations of APS1, additional APS1-specific autoantibodies, and DNA sequence and copy number variations of AIRE.

Results: In total, 17 patients (2.5%) displayed autoantibodies against interleukin-22 and/or interferon-α4, of which nine were known APS1 cases. Four patients previously undiagnosed with APS1 fulfilled clinical, genetic, and serological criteria. Hence, we identified four patients with undiagnosed APS1 with this screening procedure.

Conclusion: We propose that patients with Addison disease should be routinely screened for cytokine autoantibodies. Clinical or serological support for APS1 should warrant DNA sequencing and copy number analysis of AIRE to enable early diagnosis and prevention of lethal complications.

National Category
Endocrinology and Diabetes Immunology in the medical area Rheumatology and Autoimmunity
Identifiers
urn:nbn:se:uu:diva-343355 (URN)10.1210/jc.2017-01957 (DOI)000424934300021 ()29069385 (PubMedID)
Funder
Swedish Research CouncilRagnar Söderbergs stiftelseTorsten Söderbergs stiftelseEU, FP7, Seventh Framework Programme, 201167Stockholm County CouncilSwedish Society for Medical Research (SSMF)Swedish Society of MedicineNovo NordiskÅke Wiberg Foundation
Available from: 2018-02-26 Created: 2018-02-26 Last updated: 2018-04-24Bibliographically 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
Show others...
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
Dalin, F., Adamus, G., Yang, S., Landgren, E., Palle, J., Hallgren, Å., . . . Alimohammadi, M. (2016). Aryl Hydrocarbon Receptor-Interacting Protein-Like 1 in Cancer-Associated Retinopathy. Ophthalmology (Rochester, Minn.), 123(6), 1401-1404
Open this publication in new window or tab >>Aryl Hydrocarbon Receptor-Interacting Protein-Like 1 in Cancer-Associated Retinopathy
Show others...
2016 (English)In: Ophthalmology (Rochester, Minn.), ISSN 0161-6420, E-ISSN 1549-4713, Vol. 123, no 6, p. 1401-1404Article in journal, Editorial material (Other academic) Published
National Category
Ophthalmology
Identifiers
urn:nbn:se:uu:diva-299646 (URN)10.1016/j.ophtha.2015.12.031 (DOI)000376506400041 ()26854037 (PubMedID)
Available from: 2016-07-26 Created: 2016-07-25 Last updated: 2017-11-28Bibliographically approved
Dalin, F., Adamus, G., Yang, S., Landgren, E., Palle, J., Hallgren, Å., . . . Alimohammadi, M. (2016). Aryl Hydrocarbon Receptor-Interacting Protein-Like 1 in Cancer-Associated Retinopathy. Ophthalmology (Rochester, Minn.), 123(6), 1401-1404
Open this publication in new window or tab >>Aryl Hydrocarbon Receptor-Interacting Protein-Like 1 in Cancer-Associated Retinopathy
Show others...
2016 (English)In: Ophthalmology (Rochester, Minn.), ISSN 0161-6420, E-ISSN 1549-4713, Vol. 123, no 6, p. 1401-1404Article in journal (Refereed) Published
National Category
Cancer and Oncology
Research subject
Molecular Medicine
Identifiers
urn:nbn:se:uu:diva-279019 (URN)10.1016/j.ophtha.2015.12.031 (DOI)
Available from: 2016-02-27 Created: 2016-02-27 Last updated: 2017-11-30Bibliographically approved
Eriksson, D., Bianchi, M., Landegren, N., Nordin, J., Dalin, F., Mathioudaki, A., . . . Pielberg, G. R. (2016). Extended exome sequencing identifies BACH2 as a novel major risk locus for Addison's disease. Journal of Internal Medicine, 286(6), 595-608
Open this publication in new window or tab >>Extended exome sequencing identifies BACH2 as a novel major risk locus for Addison's disease
Show others...
2016 (English)In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 286, no 6, p. 595-608Article in journal (Refereed) Published
Abstract [en]

BackgroundAutoimmune disease is one of the leading causes of morbidity and mortality worldwide. In Addison's disease, the adrenal glands are targeted by destructive autoimmunity. Despite being the most common cause of primary adrenal failure, little is known about its aetiology. MethodsTo understand the genetic background of Addison's disease, we utilized the extensively characterized patients of the Swedish Addison Registry. We developed an extended exome capture array comprising a selected set of 1853 genes and their potential regulatory elements, for the purpose of sequencing 479 patients with Addison's disease and 1394 controls. ResultsWe identified BACH2 (rs62408233-A, OR = 2.01 (1.71-2.37), P = 1.66 x 10(-15), MAF 0.46/0.29 in cases/controls) as a novel gene associated with Addison's disease development. We also confirmed the previously known associations with the HLA complex. ConclusionWhilst BACH2 has been previously reported to associate with organ-specific autoimmune diseases co-inherited with Addison's disease, we have identified BACH2 as a major risk locus in Addison's disease, independent of concomitant autoimmune diseases. Our results may enable future research towards preventive disease treatment.

Keywords
Addison Disease, BACH2 protein, genetic, genetic association studies, genetic predisposition to disease, human, polymorphism
National Category
General Practice
Identifiers
urn:nbn:se:uu:diva-311491 (URN)10.1111/joim.12569 (DOI)000388573300007 ()27807919 (PubMedID)
Funder
Swedish Research CouncilRagnar Söderbergs stiftelseTorsten Söderbergs stiftelseEU, European Research Council, 201167Stockholm County CouncilThe Karolinska Institutet's Research FoundationSwedish Society for Medical Research (SSMF)Swedish Society of MedicineNovo NordiskSwedish Research Council FormasSwedish Rheumatism AssociationÅke Wiberg FoundationAstraZeneca
Available from: 2016-12-28 Created: 2016-12-28 Last updated: 2018-01-13Bibliographically approved
Landegren, N., Sharon, D., Freyhult, E., Hallgren, Å., Eriksson, D., Edqvist, P.-H., . . . Kämpe, O. (2016). Proteome-wide survey of the autoimmune target repertoire in autoimmune polyendocrine syndrome type 1. Scientific Reports, 6, Article ID 20104.
Open this publication in new window or tab >>Proteome-wide survey of the autoimmune target repertoire in autoimmune polyendocrine syndrome type 1
Show others...
2016 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 20104Article in journal (Refereed) Published
Abstract [en]

Autoimmune polyendocrine syndrome type 1 (APS1) is a monogenic disorder that features multiple autoimmune disease manifestations. It is caused by mutations in the Autoimmune regulator (AIRE) gene, which promote thymic display of thousands of peripheral tissue antigens in a process critical for establishing central immune tolerance. We here used proteome arrays to perform a comprehensive study of autoimmune targets in APS1. Interrogation of established autoantigens revealed highly reliable detection of autoantibodies, and by exploring the full panel of more than 9000 proteins we further identified MAGEB2 and PDILT as novel major autoantigens in APS1. Our proteome-wide assessment revealed a marked enrichment for tissue-specific immune targets, mirroring AIRE's selectiveness for this category of genes. Our findings also suggest that only a very limited portion of the proteome becomes targeted by the immune system in APS1, which contrasts the broad defect of thymic presentation associated with AIRE-deficiency and raises novel questions what other factors are needed for break of tolerance.

Keywords
autoimmune
National Category
Immunology in the medical area
Identifiers
urn:nbn:se:uu:diva-276128 (URN)10.1038/srep20104 (DOI)000368996700001 ()26830021 (PubMedID)
Funder
Swedish Research CouncilSwedish Research Council FormasTorsten Söderbergs stiftelseRagnar Söderbergs stiftelseNovo Nordisk
Available from: 2016-02-09 Created: 2016-02-09 Last updated: 2018-01-10Bibliographically approved
Landegren, N. (2015). Biomarker Discovery in Tissue-specific Autoimmune Disease. (Doctoral dissertation). Uppsala: Acta Universitatis Upsaliensis
Open this publication in new window or tab >>Biomarker Discovery in Tissue-specific Autoimmune Disease
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Autoimmune diseases encompass a diverse group of disorders that collectively affect 5% of the population. Despite large clinical variability, autoimmune disorders share a common etiology in that they all develop from immune responses against self. T-cell receptors and antibodies recognize distinct self-molecules and direct destructive effector mechanisms to the target organs. Characterization of autoimmune targets can help in the understanding autoimmune disease features and is of additional importance for subsequent use in clinical diagnosis.

Rare monogenic disorder can provide an access to the study and understanding of mechanisms underlying common and more complex diseases. Autoimmune polyendocrine syndrome type 1 (APS1) is an autosomal recessive disorder caused by mutations in the AIRE gene, and is a valuable model of tissue-specific autoimmune disease. APS1 patients develop multiple autoimmune disease manifestations and display autoantibodies against the affected tissues.

Recent development in protein array technology has opened a novel avenue for explorative biomarker studies in autoimmune disorders. Present-day protein arrays contain many thousands of full-length human proteins and enable autoantibody screens at the proteome-scale.

In the current work I have utilized proteome arrays to perform a comprehensive study of autoimmune targets in APS1. Survey of established autoantigens revealed highly reliable detection of autoantibodies, and by exploring the full panel of 9000 proteins we further identified three novel, major autoantigens. Our findings revealed a marked enrichment for tissue-specific immune targets and further suggest that only a very limited portion of the proteome becomes targeted by the immune system in APS1. This work identifies prostatic transglutaminase 4 as novel male-specific autoantigen. In the mouse model of APS1 we could link TGM4 immunity with a tissue-destructive prostatitis, a compromised prostatic secretion of TGM4 and with defect in the establishment of central immune tolerance for TGM4. Our findings suggest prostate autoimmunity is a major manifestation in male APS1 patients with potential role in development of subfertility. In this doctoral work we also report on collecting duct autoantibodies in APS1 patients with interstitial nephritis and on the identification of aquaporin 2 as a collecting duct autoantigen. Collectively, the present investigations provide an overview-perspective on the autoimmune target repertoire in APS1 and identify novel autoimmune manifestations of the syndrome.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2015. p. 56
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1153
National Category
Basic Medicine
Identifiers
urn:nbn:se:uu:diva-265284 (URN)978-91-554-9391-2 (ISBN)
Public defence
2015-12-17, Enghoffsalen, Ing. 50, UAS, Uppsala, 09:15 (Swedish)
Opponent
Supervisors
Available from: 2015-11-26 Created: 2015-10-26 Last updated: 2018-01-10
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-6163-9540

Search in DiVA

Show all publications