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Enerbäck, Charlotta
Publications (10 of 36) Show all publications
Sigurdardottir, G., Ekman, A.-K., Verma, D. & Enerbäck, C. (2018). Decreased Systemic Levels of Endocan-1 and CXCL16 in Psoriasis Are Restored following Narrowband UVB Treatment.. Dermatology, 234(5-6), 173-179
Open this publication in new window or tab >>Decreased Systemic Levels of Endocan-1 and CXCL16 in Psoriasis Are Restored following Narrowband UVB Treatment.
2018 (English)In: Dermatology, ISSN 1018-8665, E-ISSN 1421-9832, Vol. 234, no 5-6, p. 173-179Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: In psoriasis, a common immune-mediated disease affecting 2-3% of the population worldwide, there is an increased prevalence of extracutaneous diseases including obesity, the metabolic syndrome, and cardiovascular disease. This is believed to be linked to systemic inflammation. In previous studies, we have explored various markers in plasma and serum to characterize the ongoing systemic inflammation in psoriasis patients compared to controls. We have identified several markers that were altered in psoriasis patients, but which all were unresponsive to narrowband UVB (NB-UVB) treatment.

OBJECTIVE: The objective of the study was to evaluate the effect of NB-UVB treatment on markers of cardiovascular risk and systemic inflammation in psoriasis.

METHODS: The levels of 17 potential biomarkers with an association with cardiovascular risk were quantitated in plasma from 37 age- and gender-matched psoriasis patients and controls at baseline and in 21 psoriasis patients after 12 weeks of NB-UVB treatment to identify a systemic treatment response.

RESULTS: We identified the mediators endocan-1, CXCL16, and sVEGFR1, which were systemically decreased in psoriasis at baseline, as well as FABP3, FABP4, and sIL-1R1, which showed normal baseline levels. After 10-12 weeks of NB-UVB treatment, endocan-1 and CXCL16 were restored to normal levels, while sVEGFR1, FABP3, FABP4, and sIL-1R1 showed a significant reduction.

CONCLUSION: The current study expands the number of potential biomarkers in psoriasis by including a greater number and variety of mediators, approaching the systemic inflammation from additional vantage points, including soluble immune receptors and adipocyte contribution, to provide a more complete picture of the systemic inflammatory state in psoriasis.

Place, publisher, year, edition, pages
Basel: S. Karger, 2018
Keywords
Cardiovascular risk, Psoriasis, Skin, UVB
National Category
Dermatology and Venereal Diseases
Identifiers
urn:nbn:se:liu:diva-151989 (URN)10.1159/000491819 (DOI)000451050100003 ()30176661 (PubMedID)
Funder
Ingrid Asp Psoriasis Research Center
Note

This research was funded by the Ingrid Asp Foundation, the Welander Foundation, the Swedish Psoriasis Association, and the Medical Research Council.

Available from: 2018-10-12 Created: 2018-10-12 Last updated: 2019-05-01
Ekman, A.-K., Vegfors, J., Bivik, C. & Enerbäck, C. (2017). Overexpression of Psoriasin (S100A7) Contributes to Dysregulated Differentiation in Psoriasis.. Acta Dermato-Venereologica, 97(4), 441-448
Open this publication in new window or tab >>Overexpression of Psoriasin (S100A7) Contributes to Dysregulated Differentiation in Psoriasis.
2017 (English)In: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, Vol. 97, no 4, p. 441-448Article in journal (Refereed) Published
Abstract [en]

Psoriasin, which is highly expressed in psoriasis, is encoded by a gene located within the epidermal differentiation complex. The aim of this study was to investigate the effect of endogenous psoriasin on disturbed keratinocyte differentiation in psoriasis. Immunohistochemical staining revealed a gradient of psoriasin expression in the psoriatic epidermis with highest expression in the suprabasal, differentiated layers. Induction of keratinocyte differentiation caused concurrent expression of psoriasin and the differentiation marker involucrin. The differentiation-induced psoriasin expression was found to be mediated by the protein kinase C pathway. The downregulation of psoriasin expression by small interfering RNA revealed that psoriasin mediates the expression of involucrin, desmoglein 1, transglutaminase 1 and CD24 in normal differentiation. The lentivirus-mediated overexpression of psoriasin, mimicking the psoriatic milieu, gave rise to an altered regulation of differentiation genes and an expression pattern reminiscent of that in psoriatic epidermis. These findings suggest that psoriasin contributes to the dysregulated differentiation process in the psoriasis epidermis.

Place, publisher, year, edition, pages
Society for the Publication of Acta Dermato - Venereologica, 2017
National Category
Dermatology and Venereal Diseases
Identifiers
urn:nbn:se:liu:diva-133860 (URN)10.2340/00015555-2596 (DOI)000401127000005 ()27958610 (PubMedID)
Note

Funding agencies: Ingrid Asp Foundation; Welander Foundation; Swedish psoriasis association; Medical Research Council

Available from: 2017-01-12 Created: 2017-01-12 Last updated: 2018-05-02Bibliographically approved
Ekman, A.-K. & Enerbäck, C. (2016). Lack of preclinical support for the efficacy of histone deacetylase inhibitors in the treatment of psoriasis. [Letter to the editor]. British Journal of Dermatology, 174(2), 424-426
Open this publication in new window or tab >>Lack of preclinical support for the efficacy of histone deacetylase inhibitors in the treatment of psoriasis.
2016 (English)In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 174, no 2, p. 424-426Article in journal, Letter (Refereed) Published
Place, publisher, year, edition, pages
Wiley-Blackwell, 2016
National Category
Dermatology and Venereal Diseases
Identifiers
urn:nbn:se:liu:diva-125471 (URN)10.1111/bjd.14021 (DOI)000370014600037 ()26153825 (PubMedID)
Available from: 2016-02-24 Created: 2016-02-24 Last updated: 2017-05-03
Tsoi, L. C., Spain, S. L., Ellinghaus, E., Stuart, P. E., Capon, F., Knight, J., . . . Elder, J. T. (2015). Enhanced meta-analysis and replication studies identify five new psoriasis susceptibility loci. Nature Communications, 6(7001)
Open this publication in new window or tab >>Enhanced meta-analysis and replication studies identify five new psoriasis susceptibility loci
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2015 (English)In: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 6, no 7001Article in journal (Refereed) Published
Abstract [en]

Psoriasis is a chronic autoimmune disease with complex genetic architecture. Previous genome-wide association studies (GWAS) and a recent meta-analysis using Immunochip data have uncovered 36 susceptibility loci. Here, we extend our previous meta-analysis of European ancestry by refined genotype calling and imputation and by the addition of 5,033 cases and 5,707 controls. The combined analysis, consisting of over 15,000 cases and 27,000 controls, identifies five new psoriasis susceptibility loci at genome-wide significance (Pless than5 x 10(-8)). The newly identified signals include two that reside in intergenic regions (1q31.1 and 5p13.1) and three residing near PLCL2 (3p24.3), NFKBIZ (3q12.3) and CAMK2G (10q22.2). We further demonstrate that NFKBIZ is a TRAF3IP2-dependent target of IL-17 signalling in human skin keratinocytes, thereby functionally linking two strong candidate genes. These results further integrate the genetics and immunology of psoriasis, suggesting new avenues for functional analysis and improved therapies.

Place, publisher, year, edition, pages
Nature Publishing Group: Nature Communications, 2015
National Category
Dermatology and Venereal Diseases
Identifiers
urn:nbn:se:liu:diva-119808 (URN)10.1038/ncomms8001 (DOI)000355529100004 ()25939698 (PubMedID)
Note

Funding Agencies|National Institutes of Health [R01AR042742, R01AR050511, R01AR054966, R01AR062382, R01AR065183]; Wellcome Trust; German Research Foundation; Medical Research Council [G0000934]; Wellcome Trust [068545/Z/02]; Medical Research Council Stratified Medicine award [MR/L011808/1]; German Ministry of Education and Research (BMBF) through the e:Med sysINFLAME grant; Doris Duke Foundation; Department of Health via the NIHR comprehensive Biomedical Research Center award; Kings College London; KCH NHS Foundation Trust; Heinz Nixdorf Foundation; Estonian Ministry of Education and Research [IUT20-46]; Centre of Translational Genomics of University of Tartu (SP1GVARENG); European Regional Development Fund (Centre of Translational Medicine, University of Tartu); German Federal Ministry of Education and Research (BMBF); Ann Arbor Veterans Affairs Hospital

Available from: 2015-06-26 Created: 2015-06-26 Last updated: 2017-12-04
Stuart, P. E., Nair, R. P., Tsoi, L. C., Tejasvi, T., Das, S., Min Kang, H., . . . Elder, J. T. (2015). Genome-wide Association Analysis of Psoriatic Arthritis and Cutaneous Psoriasis Reveals Differences in Their Genetic Architecture. American Journal of Human Genetics, 97(6), 816-836
Open this publication in new window or tab >>Genome-wide Association Analysis of Psoriatic Arthritis and Cutaneous Psoriasis Reveals Differences in Their Genetic Architecture
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2015 (English)In: American Journal of Human Genetics, ISSN 0002-9297, E-ISSN 1537-6605, Vol. 97, no 6, p. 816-836Article in journal (Refereed) Published
Abstract [en]

Psoriasis vulgaris (PsV) is a common inflammatory and hyperproliferative skin disease. Up to 30% of people with PsV eventually develop psoriatic arthritis (PsA), an inflammatory musculoskeletal condition. To discern differences in genetic risk factors for PsA and cutaneous-only psoriasis (PsC), we carried out a genome-wide association study (GWAS) of 1,430 PsA case subjects and 1,417 unaffected control subjects. Meta-analysis of this study with three other GWASs and two targeted genotyping studies, encompassing a total of 9,293 PsV case subjects, 3,061 PsA case subjects, 3,110 PsC case subjects, and 13,670 unaffected control subjects of European descent, detected 10 regions associated with PsA and 11 with PsC at genome-wide (GW) significance. Several of these association signals (IFNLR1, IFIH1, NFKBIA for PsA; TNFRSF9, LCE3C/B, TRAF3IP2, IL23A, NFKBIA for PsC) have not previously achieved GW significance. After replication, we also identified a PsV-associated SNP near CDKAL1 (rs4712528, odds ratio [OR] = 1.16, p = 8.4 x 10(-11)). Among identified psoriasis risk variants, three were more strongly associated with PsC than PsA (rs12189871 near HLA-C, p = 5.0 x 10(-19); rs4908742 near TNFRSF9, p = 0.00020; rs10888503 near LCE3A, p = 0.0014), and two were more strongly associated with PsA than PsC (rs12044149 near IL23R, p = 0.00018; rs9321623 near TNFAIP3, p = 0.00022). The PsA-specific variants were independent of previously identified psoriasis variants near IL23R and TNFAIP3. We also found multiple independent susceptibility variants in the IL12B, NOS2, and IFIH1 regions. These results provide insights into the pathogenetic similarities and differences between PsC and PsA.

Place, publisher, year, edition, pages
CELL PRESS, 2015
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-125163 (URN)10.1016/j.ajhg.2015.10.019 (DOI)000368437900004 ()26626624 (PubMedID)
Note

Funding Agencies|Barbara and Neal Henschel Charitable Foundation; NIH [R01AR042742, R01AR050511, R01AR054966, R01AR063611, R01AR065183, R01AR050266]; German Research Foundation; German Ministry of Education and Research (BMBF); Doris Duke Foundation [2013106]; Taubman Medical Research Institute; Estonian Ministry of Education and Research [IUT20-46]; Centre of Translational Genomics of University of Tartu (SP1GVARENG); European Regional Development Fund (Centre of Translational Medicine, University of Tartu); Ann Arbor Veterans Affairs Hospital

Available from: 2016-02-15 Created: 2016-02-15 Last updated: 2017-11-30
Appelqvist, F., Yhr, M., Erlandson, A., Martinsson, T. & Enerbäck, C. (2014). Deletion of the MGMT gene in familial melanoma. Genes, Chromosomes and Cancer, 53(8), 703-711
Open this publication in new window or tab >>Deletion of the MGMT gene in familial melanoma
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2014 (English)In: Genes, Chromosomes and Cancer, ISSN 1045-2257, E-ISSN 1098-2264, Vol. 53, no 8, p. 703-711Article in journal (Refereed) Published
Abstract [en]

The DNA repair gene MGMT (O-6-methylguanine-DNA methyltransferase) is important for maintaining normal cell physiology and genomic stability. Alterations in MGMT play a critical role in the development of several types of cancer, including glioblastoma, lung cancer, and colorectal cancer. The purpose of this study was to explore the function of genetic alterations in MGMT and their connection with familial melanoma (FM). Using multiplex ligation-dependent probe amplification, we identified a deletion that included the MGMT gene in one of 64 families with a melanoma predisposition living in western Sweden. The mutation segregated with the disease as a heterozygous deletion in blood-derived DNA, but a homozygous deletion including the promoter region and exon 1 was seen in tumor tissue based on Affymetrix 500K and 6.0 arrays. By sequence analysis of the MGMT gene in the other 63 families with FM from western Sweden, we identified four common polymorphisms, nonfunctional, as predominantly described in previous studies. We conclude that inherited alterations in the MGMT gene might be a rare cause of FM, and we suggest that MGMT contributes to melanoma predisposition.

Place, publisher, year, edition, pages
John Wiley & Sons, 2014
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-109115 (URN)10.1002/gcc.22180 (DOI)000337738200007 ()24801985 (PubMedID)
Available from: 2014-08-13 Created: 2014-08-11 Last updated: 2017-12-05Bibliographically approved
Nikamo, P., Cheuk, S., Lysell, J., Enerbäck, C., Bergh, K., Xu Landén, N., . . . Ståhle, M. (2014). Genetic variants of the IL22 promoter associate to onset of psoriasis before puberty and increased IL-22 production in T cells.. Journal of Investigative Dermatology, 134(6), 1535-1541
Open this publication in new window or tab >>Genetic variants of the IL22 promoter associate to onset of psoriasis before puberty and increased IL-22 production in T cells.
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2014 (English)In: Journal of Investigative Dermatology, ISSN 0022-202X, E-ISSN 1523-1747, Vol. 134, no 6, p. 1535-1541Article in journal (Refereed) Published
Abstract [en]

Most psoriasis susceptibility genes were identified in cohorts of mixed clinical phenotypes and the exploration of genes in clinical subtypes is scarce. IL-22 has an established role in host defense and in psoriasis skin pathology, reflecting the delicate balance between control of infection and immunopathology. In a case-control study, we compared the genetic association to IL22 in psoriasis onset in patients between 0-9 (n=207), 10-20 (n=394), and 21-40 (n=468) years with healthy controls (n=1,529). Logistic regression analysis revealed association to regulatory elements in the IL22 promoter confined to onset of psoriasis before puberty (odds ratio=1.45, P<0.0007). The associated variants contain putative binding sites for AhR, a potent inducer of IL-22 expression. In a luciferase assay, transcriptional activity of a high-risk gene variant resulted in 80% higher promoter activity (P=0.012) compared with a low-risk variant. Ex vivo stimulated T cells from peripheral blood were analyzed with flow cytometry. Children with psoriasis carrying a high-risk variant produced 1.7 times more IL-22 compared with low-risk variants (P=0.042). Our combined genetic and functional data support the notion that a genetic IL22 variant that promotes epithelial barrier defense is preferentially enriched in and may precipitate the onset of psoriasis at an early age.

National Category
Dermatology and Venereal Diseases
Identifiers
urn:nbn:se:liu:diva-107739 (URN)10.1038/jid.2014.5 (DOI)000336193700011 ()24390134 (PubMedID)
Available from: 2014-06-19 Created: 2014-06-19 Last updated: 2017-12-05
Ekman, A.-K., Verma, D., Fredrikson, M., Bivik, C. & Enerbäck, C. (2014). Genetic variations of NLRP1: susceptibility in psoriasis. British Journal of Dermatology, 171(6), 1517-1520
Open this publication in new window or tab >>Genetic variations of NLRP1: susceptibility in psoriasis
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2014 (English)In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 171, no 6, p. 1517-1520Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: NACHT, LRR and PYD domain-containing protein (NLRP)1 is part of the inflammasome multiprotein complex involved in the production of interleukin (IL)-1β and IL-18, two cytokines strongly implicated in psoriasis pathogenesis. Genetic variations in NLRP1 are associated with a predisposition for chronic inflammatory conditions.

OBJECTIVES: The aim of the study was to investigate the role of genetic variation in the NLRP1 inflammasome in psoriasis susceptibility.

MATERIAL AND METHODS: Four haplotype-tagging single-nucleotide polymorphisms (SNPs) (rs6502867, rs8079034, rs878329 and rs12150220) were investigated by TaqMan allelic discrimination in a patient sample comprising 1847 individuals from 478 families and 802 healthy controls.

RESULTS: Using the transmission disequilibrium test, a significant increase in the transmission of the NLRP1 rs8079034C and rs878329C alleles to patients with psoriasis was demonstrated (P = 0·006 and P = 0·033, respectively). Furthermore, homozygosity for the rs878329C allele correlated with a younger age of onset. We also observed an increase in the expression of NLRP1 mRNA in the peripheral blood cells of patients with psoriasis. This was accompanied by a higher level of circulating IL-18 and appeared to be associated with the rs878329C allele.

CONCLUSIONS: Our data support the involvement of NLRP1 and the NLRP1 inflammasome in psoriasis susceptibility and further support the role of innate immunity in psoriasis.

Place, publisher, year, edition, pages
Wiley-Blackwell, 2014
National Category
Clinical Medicine Basic Medicine
Identifiers
urn:nbn:se:liu:diva-112730 (URN)10.1111/bjd.13178 (DOI)000347236100197 ()24909542 (PubMedID)
Note

The study was funded by the Ingrid Asp foundation, the Welander Foundation and the Swedish Psoriasis Association.

Available from: 2014-12-10 Created: 2014-12-10 Last updated: 2018-01-11Bibliographically approved
Tuominen, R., Jonsson, G., Enerbäck, C., Appelqvist, F., Olsson, H., Ingvar, C., . . . Hoiom, V. (2014). Investigation of a putative melanoma susceptibility locus at chromosome 3q29. Cancer Genetics, 207(3), 70-74
Open this publication in new window or tab >>Investigation of a putative melanoma susceptibility locus at chromosome 3q29
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2014 (English)In: Cancer Genetics, ISSN 2210-7762, E-ISSN 2210-7770, Vol. 207, no 3, p. 70-74Article in journal (Refereed) Published
Abstract [en]

Malignant melanoma, the most fatal form of skin cancer, is currently increasing in incidence in many populations. Approximately 10% of all cases occur in families with an inherited predisposition for melanoma. In Sweden, only a minor portion of such melanoma families carry a mutation in the known melanoma gene CDKN2A, and there is a need to identify additional melanoma susceptibility genes. In a recently performed genome-wide linkage screen, novel loci with suggestive evidence of linkage to melanoma were detected. In this study, we have further analyzed one region on chromosome 3q29. In all, 89 affected and 15 nonaffected family members from 42 melanoma-prone families were genotyped for 34 genetic markers. In a pooled linkage analysis of all 42 families, we detected significant evidence of linkage, with a maximum heterogeneity logarithm of odds (HLOD) score of 3.1 with 83% of the families contributing to the linkage score. The minimum critical region of linkage (defined by a 1LOD score support interval) maps to chromosome 3q29, spans 3.5 Mb of genomic sequence, and harbors 44 identified genes. Sequence variants within this region have previously been associated with cancer susceptibility. This study reports the presence of a putative novel melanoma susceptibility locus in the Swedish population, a finding that needs to be replicated in an independent study on other individuals with familial melanoma. Sequencing of genes in the region may identify novel melanoma-associated mutations.

Place, publisher, year, edition, pages
Elsevier, 2014
Keywords
Candidate genes; familial cancer; linkage analysis; melanoma; susceptibility locus
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-106986 (URN)10.1016/j.cancergen.2014.02.007 (DOI)000335539200003 ()
Available from: 2014-06-03 Created: 2014-06-02 Last updated: 2017-12-05
Thunell, L., Bivik, C., Wäster, P., Fredrikson, M., Stjernstrom, A., Synnerstad, I., . . . Enerbäck, C. (2014). MDM2 SNP309 promoter polymorphism confers risk for hereditary melanoma. Melanoma research, 24(3), 190-197
Open this publication in new window or tab >>MDM2 SNP309 promoter polymorphism confers risk for hereditary melanoma
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2014 (English)In: Melanoma research, ISSN 0960-8931, E-ISSN 1473-5636, Vol. 24, no 3, p. 190-197Article in journal (Refereed) Published
Abstract [en]

The p53 pathway regulates stress response, and variations in p53, MDM2, and MDM4 may predispose an individual to tumor development. The aim of this study was to study the impact of genetic variation on sporadic and hereditary melanoma. We have analyzed a combination of three functionally relevant variants of the p53 pathway in 258 individuals with sporadic malignant melanomas, 50 with hereditary malignant melanomas, and 799 healthy controls. Genotyping was performed by PCR-restriction fragment length polymorphism, pyrosequencing, and allelic discrimination. We found an increased risk for hereditary melanoma in MDM2 GG homozygotes, which was more pronounced among women (P=0.035). In the event of pairwise combinations of the single nucleotide polymorphisms, a risk elevation was shown for MDM2 GG homozygotes/p53 wild-type Arg in hereditary melanoma (P=0.01). Individuals with sporadic melanomas of the superficial spreading type, including melanoma in situ, showed a slightly higher frequency of the MDM2 GG genotype compared with those with nodular melanomas (P=0.04). The dysplastic nevus phenotype, present in the majority of our hereditary melanoma cases and also in some sporadic cases, further enhanced the effect of the MDM2 GG genotype on melanoma risk (P=0.005). In conclusion, the results show an association between MDM2 SNP309 and an increased risk for hereditary melanoma, especially among women. Analysis of sporadic melanoma also shows an association between MDM2 and the superficial spreading melanoma subtype, as well as an association with the presence of dysplastic nevi in sporadic melanoma.

Place, publisher, year, edition, pages
Lippincott, Williams andamp; Wilkins, 2014
Keywords
superficial spreading melanoma; MDM2; hereditary melanoma; MDM4; p53; dysplastic nevi
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-107446 (URN)10.1097/CMR.0000000000000063 (DOI)000335683500002 ()
Available from: 2014-06-12 Created: 2014-06-12 Last updated: 2017-12-05
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