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Kämpe, Olle
Alternative names
Publications (10 of 93) Show all publications
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
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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
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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
Zaidi, G., Bhatia, V., Sahoo, S. K., Sarangi, A. N., Bharti, N., Zhang, L., . . . Bhatia, E. (2017). Autoimmune polyendocrine syndrome type 1 in an Indian cohort: a longitudinal study. Endocrine Connections, 6(5), 289-296
Open this publication in new window or tab >>Autoimmune polyendocrine syndrome type 1 in an Indian cohort: a longitudinal study
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2017 (English)In: Endocrine Connections, ISSN 2049-3614, E-ISSN 2049-3614, Vol. 6, no 5, p. 289-296Article in journal (Refereed) Published
Abstract [en]

Objective: Autoimmune polyendocrine syndrome type 1 (APS1) is a rare autosomal recessive disorder characterized by progressive organ-specific autoimmunity. There is scant information on APS1 in ethnic groups other than European Caucasians. We studied clinical aspects and autoimmune regulator (AIRE) gene mutations in a cohort of Indian APS1 patients. Design: Twenty-three patients (19 families) from six referral centres in India, diagnosed between 1996 and 2016, were followed for [median (range)] 4 (0.2-19) years. Methods: Clinical features, mortality, organ-specific autoantibodies and AIRE gene mutations were studied. Results: Patients varied widely in their age of presentation [3.5 (0.1-17) years] and number of clinical manifestations [5 (2-11)]. Despite genetic heterogeneity, the frequencies of the major APS1 components (mucocutaneous candidiasis: 96%; hypoparathyroidism: 91%; primary adrenal insufficiency: 55%) were similar to reports in European series. In contrast, primary hypothyroidism (23%) occurred more frequently and at an early age, while kerato-conjunctivitis, urticarial rash and autoimmune hepatitis were uncommon (9% each). Six (26%) patients died at a young age [5.8 (3-23) years] due to septicaemia, hepatic failure and adrenal/hypocalcaemic crisis from non-compliance/unexplained cause. Interferon-a and/or interleukin-22 antibodies were elevated in all 19 patients tested, including an asymptomatic infant. Eleven AIRE mutations were detected, the most common being p.C322fsX372 (haplotype frequency 37%). Four mutations were novel, while six others were previously described in European Caucasians. Conclusions: Indian APS1 patients exhibited considerable genetic heterogeneity and had highly variable clinical features. While the frequency of major manifestations was similar to that of European Caucasians, other features showed significant differences. A high mortality at a young age was observed.

Keywords
autoimmune polyendocrine syndrome 1, APECED syndrome, autoimmune regulator gene, India
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-330021 (URN)10.1530/EC-17-0022 (DOI)000404929500002 ()28446514 (PubMedID)
Funder
Swedish Research CouncilTorsten Söderbergs stiftelseRagnar Söderbergs stiftelse
Available from: 2017-10-11 Created: 2017-10-11 Last updated: 2017-11-29Bibliographically approved
Smith-Anttila, C. J. A., Bensing, S., Alimohammadi, M., Dalin, F., Oscarson, M., Zhang, M.-D., . . . Kämpe, O. (2017). Identification of endothelin-converting enzyme-2 as an autoantigen in autoimmune polyendocrine syndrome type 1. Autoimmunity, 50(4), 223-231
Open this publication in new window or tab >>Identification of endothelin-converting enzyme-2 as an autoantigen in autoimmune polyendocrine syndrome type 1
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2017 (English)In: Autoimmunity, ISSN 0891-6934, E-ISSN 1607-842X, Vol. 50, no 4, p. 223-231Article in journal (Refereed) Published
Abstract [en]

Autoimmune polyendocrine syndrome type 1 (APS1) is a rare monogenic autoimmune disorder caused by mutations in the autoimmune regulator (AIRE) gene. High titer autoantibodies are a characteristic feature of APS1 and are often associated with particular disease manifestations. Pituitary deficits are reported in up to 7% of all APS1 patients, with immunoreactivity to pituitary tissue frequently reported. We aimed to isolate and identify specific pituitary autoantigens in patients with APS1. Immunoscreening of a pituitary cDNA expression library identified endothelin-converting enzyme (ECE)-2 as a potential candidate autoantigen. Immunoreactivity against ECE-2 was detected in 46% APS1 patient sera, with no immunoreactivity detectable in patients with other autoimmune disorders or healthy controls. Quantitative-PCR showed ECE-2 mRNA to be most abundantly expressed in the pancreas with high levels also in the pituitary and brain. In the pancreas ECE-2 was co-expressed with insulin or somatostatin, but not glucagon and was widely expressed in GH producing cells in the guinea pig pituitary. The correlation between immunoreactivity against ECE-2 and the major recognized clinical phenotypes of APS1 including hypopituitarism was not apparent. Our results identify ECE-2 as a specific autoantigen in APS1 with a restricted neuroendocrine distribution.

Keywords
APS1, endothelin-converting enzyme-2, ECE-2, pituitary autoantibodies, pancreas
National Category
Immunology
Identifiers
urn:nbn:se:uu:diva-333619 (URN)10.1080/08916934.2017.1332183 (DOI)000407564500005 ()28557628 (PubMedID)
Available from: 2017-11-16 Created: 2017-11-16 Last updated: 2017-11-16Bibliographically approved
Navarini, A. A., Hruz, P., Berger, C. T., Hou, T. Z., Schwab, C., Gabrysch, A., . . . Recher, M. (2017). Vedolizumab as a successful treatment of CTLA-4-associated autoimmune enterocolitis [Letter to the editor]. Journal of Allergy and Clinical Immunology, 139(3), 1043-1046
Open this publication in new window or tab >>Vedolizumab as a successful treatment of CTLA-4-associated autoimmune enterocolitis
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2017 (English)In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 139, no 3, p. 1043-1046Article in journal, Letter (Refereed) Published
Place, publisher, year, edition, pages
MOSBY-ELSEVIER, 2017
National Category
Respiratory Medicine and Allergy Immunology in the medical area
Identifiers
urn:nbn:se:uu:diva-320972 (URN)10.1016/j.jaci.2016.08.042 (DOI)000397295800041 ()27908448 (PubMedID)
Available from: 2017-04-27 Created: 2017-04-27 Last updated: 2018-01-13Bibliographically 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
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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
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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
Landegren, N., Pourmousa Lindberg, M., Skov, J., Hallgren, Å., Eriksson, D., Lisberg Toft-Bertelsen, T., . . . Kämpe, O. (2016). Autoantibodies Targeting a Collecting Duct-Specific Water Channel in Tubulointerstitial Nephritis.. Journal of the American Society of Nephrology, 27(10), 3220-3228
Open this publication in new window or tab >>Autoantibodies Targeting a Collecting Duct-Specific Water Channel in Tubulointerstitial Nephritis.
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2016 (English)In: Journal of the American Society of Nephrology, ISSN 1046-6673, E-ISSN 1533-3450, Vol. 27, no 10, p. 3220-3228Article in journal (Refereed) Published
Abstract [en]

Tubulointerstitial nephritis is a common cause of kidney failure and may have diverse etiologies. This form of nephritis is sometimes associated with autoimmune disease, but the role of autoimmune mechanisms in disease development is not well understood. Here, we present the cases of three patients with autoimmune polyendocrine syndrome type 1 who developed tubulointerstitial nephritis and ESRD in association with autoantibodies against kidney collecting duct cells. One of the patients developed autoantibodies targeting the collecting duct-specific water channel aquaporin 2, whereas autoantibodies of the two other patients reacted against the HOXB7 or NFAT5 transcription factors, which regulate the aquaporin 2 promoter. Our findings suggest that tubulointerstitial nephritis developed in these patients as a result of an autoimmune insult on the kidney collecting duct cells.

National Category
Rheumatology and Autoimmunity
Research subject
Medical Science
Identifiers
urn:nbn:se:uu:diva-300411 (URN)10.1681/ASN.2015101126 (DOI)000384628500030 ()26984885 (PubMedID)
Funder
Swedish Research CouncilSwedish Research Council FormasSwedish Rheumatism AssociationNovo NordiskTorsten Söderbergs stiftelseRagnar Söderbergs stiftelse
Available from: 2016-08-08 Created: 2016-08-08 Last updated: 2017-11-28Bibliographically approved
Blokzijl, A., Chen, L., Gustafsdottir, S. M., Vuu, J., Ullenhag, G., Kämpe, O., . . . Hedstrand, H. (2016). Elevated Levels of SOX10 in Serum from Vitiligo and Melanoma Patients, Analyzed by Proximity Ligation Assay. PLoS ONE, 11(4), Article ID e0154214.
Open this publication in new window or tab >>Elevated Levels of SOX10 in Serum from Vitiligo and Melanoma Patients, Analyzed by Proximity Ligation Assay
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2016 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 4, article id e0154214Article in journal (Refereed) Published
Abstract [en]

Background

The diagnosis of malignant melanoma currently relies on clinical inspection of the skin surface and on the histopathological status of the excised tumor. The serum marker S100B is used for prognostic estimates at later stages of the disease, but analyses are marred by false positives and inadequate sensitivity in predicting relapsing disorder.

Objectives

To investigate SOX10 as a potential biomarker for melanoma and vitiligo.

Methods

In this study we have applied proximity ligation assay (PLA) to detect the transcription factor SOX10 as a possible serum marker for melanoma. We studied a cohort of 110 melanoma patients. We further investigated a second cohort of 85 patients with vitiligo, which is a disease that also affects melanocytes.

Results

The specificity of the SOX10 assay in serum was high, with only 1% of healthy blood donors being positive. In contrast, elevated serum SOX10 was found with high frequency among vitiligo and melanoma patients. In patients with metastases, lack of SOX10 detection was associated with treatment benefit. In two responding patients, a change from SOX10 positivity to undetectable levels was seen before the response was evident clinically.

Conclusions

We show for the first time that SOX10 represents a promising new serum melanoma marker for detection of early stage disease, complementing the established S100B marker. Our findings imply that SOX10 can be used to monitor responses to treatment and to assess if the treatment is of benefit at stages earlier than what is possible radiologically.

Keywords
sox10 proximity ligation assay
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-289194 (URN)10.1371/journal.pone.0154214 (DOI)000374970600050 ()27110718 (PubMedID)
Funder
EU, FP7, Seventh Framework Programme, 294409EU, FP7, Seventh Framework Programme, 316929Swedish Research Council
Available from: 2016-04-29 Created: 2016-04-29 Last updated: 2018-01-10Bibliographically 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
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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
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