Publications by authors named "Tove Christensen"

49 Publications

Is there a potential international market for Danish welfare pork? - A consumer survey from Denmark, Sweden, and Germany.

Meat Sci 2021 Jun 30;183:108616. Epub 2021 Jun 30.

Department of Food and Resource Economics, University of Copenhagen, Rolighedsvej 23, DK-1958 Frederiksberg C, Denmark; Department of Veterinary and Animal Sciences, University of Copenhagen, Grønnegårdsvej 8, DK-1870 Frederiksberg C, Denmark.

This cross-country study investigates the potential to improve pig welfare by exploiting consumer demand, domestically and in export markets, for welfare pork produced in indoor production systems. The analysis is based on questionnaire data collected in 2019 focusing on demand for Danish welfare pork both in Denmark and in two nearby export markets, Sweden and Germany. To reduce hypothetical bias, a willingness-to-pay indicator is combined with an indicator of positive interest in buying a fictive Danish welfare labelled pork. We find that the market potential is relatively weak. Our findings indicate that there is some, albeit limited, potential in Denmark and Germany while demand is practically non-existing in Sweden, probably because the pig welfare guaranteed by Swedish legislation is similar to what is provided by the fictive welfare label employed in the study. Hence, consumer demand alone cannot secure enhanced pig welfare. Moreover, we found national differences in the characteristics of consumers who are interested in Danish welfare pork.
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http://dx.doi.org/10.1016/j.meatsci.2021.108616DOI Listing
June 2021

Consumer preferences for low-salt foods: a Danish case study based on a comprehensive supermarket intervention.

Public Health Nutr 2021 Aug 12;24(12):3956-3965. Epub 2021 May 12.

Department of Food and Resource Economics, University of Copenhagen, Rolighedsvej 25, 1958Frederiksberg, Denmark.

Objective: The objective is to analyse Danish consumers' attitudes to buying food with reduced salt content.

Design: The study is based on a comprehensive store intervention that included 114 stores belonging to the same supermarket chain. Three different salt claims were tested for 8 weeks on six test products within the categories bread, cornflakes and frozen pizzas. Scanner data were supplemented with 134 brief interviews with consumers in nine selected stores.

Setting: Stores spread across Denmark.

Participants: Consumers who buy food in the stores.

Results: Statistical regression analyses of the scanner data indicated that none of the three claims significantly affected demand for any of the test products. The interviews confirmed that many consumers were more focused on other elements of the official dietary advice than reduced salt consumption, such as eating plenty of vegetables, choosing products with whole grains and reducing their intake of sugar and fat.

Conclusions: Overall, both the scanner data and the interviews pointed in the same direction, towards the conclusion that salt content is often a secondary factor when Danish consumers make dietary choices.
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http://dx.doi.org/10.1017/S1368980021002056DOI Listing
August 2021

Pig Farmers' Perceptions of Economic Incentives to Control Prevalence at Herd Level.

Front Vet Sci 2021 16;8:647697. Epub 2021 Apr 16.

Department of Food and Resource Economics, University of Copenhagen, Copenhagen, Denmark.

This paper investigates how perceived costs and benefits of control among Danish pig farmers affect the farmers' choice of action toward reducing the prevalence of in their herds. Based on data from an online questionnaire involving 163 Danish pig farmers, we find a considerable uncertainty among pig farmers about the perceived effects of the reducing actions. The results indicate large variations in the perceived costs of implementing different types of reducing actions (management-, hygiene- and feed-related). For some cases, farmers associate net benefits and positive productivity effects with implementation of the actions while studies by the industry indicate net costs to the farmers. Differences among farmers support the idea of an outcome-based penalty scheme but the large uncertainties about costs and effects of actions toward control might hamper the effectiveness of such a penalty scheme as a regulatory instrument to affect farmer behavior.
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http://dx.doi.org/10.3389/fvets.2021.647697DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8086553PMC
April 2021

Regulation of the expression of human endogenous retroviruses: elements in fetal development and a possible role in the development of cancer and neurological diseases.

APMIS 2021 May 5;129(5):241-253. Epub 2021 Apr 5.

Department of Biomedicine, Aarhus University, Aarhus C, Denmark.

Human endogenous retroviruses (HERVs) are remnants of ancient retroviral germline infections. Most HERV sequences are silenced in somatic cells, but interest is emerging on the involvement of HERV derived transcripts and proteins in human physiology and disease. A HERV-W encoded protein, syncytin-1, has been co-opted into fetal physiology, where it plays a role in trophoblast formation. Altered HERV transcription and expression of HERV derived proteins are associated with various cancer types and neurological diseases such as multiple sclerosis (MS). The implication of HERVs as potential mediators of both health and disease suggests important roles of regulatory mechanisms and alterations of these in physiological and pathological processes. The regulation of HERV sequences is mediated by a wide variety of mechanisms, and the focus of this review is on selected aspects of these, including epigenetic mechanisms such as CpG methylation and histone modifications of the HP1-H3K9me axis, viral transactivation events, and regulatory perspectives of transient stimuli in the microenvironment. Increasing knowledge of the regulation of HERV sequences will not only contribute to the understanding of complex pathogeneses, but also may pinpoint potential targets for better diagnosis and treatment in complex diseases as MS.
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http://dx.doi.org/10.1111/apm.13130DOI Listing
May 2021

Consumer preferences for reduced antibiotic use in Danish pig production.

Prev Vet Med 2021 Apr 23;189:105310. Epub 2021 Feb 23.

Department of Food and Resource Economics, University of Copenhagen, Rolighedsvej 25, Frederiksberg C, DK-1958, Denmark.

Denmark has a large and intensive pig production sector which accounts for around half of the total use of antimicrobials in Demark. The economic feasibility of alternative strategies involving reduced use of antibiotics depends not only on their effects on productivity but also on consumers' demand, and willingness-to-pay (WTP), for pork from pigs with no or lower antibiotic treatment. This study investigates the various concerns that consumers might have about the use of antibiotics in pig production, and how they affect demand and WTP. We used data from an online questionnaire survey of approximately 1000 Danish consumers. WTP estimates were obtained using payment card data analysed in an ordered probit regression. We found that 41 % of the respondents wanted antibiotic use to be reduced substantially, and that they linked reduced use of antibiotics in pig production primarily with reduced risk of antibiotic residues in pork and a lowered risk of resistant bacteria developing. A considerable share of the consumers we sampled also linked reduced antibiotic use with improved animal welfare, and with price increases for pork. Two thirds of the consumers stated a positive WTP for reduced use of antibiotics, but only one in five were willing to pay more than 10 % for pork produced using antibiotics 20 % less than average. The WTP estimates differed with socio-demographic variables (education, geography, gender and age). In addition, the respondents' perceptions of the effects of reducing antibiotic use and of externalities associated with the pig industry, and the frequency of their pork consumption, were found to affect their WTP for pork produced with lower antibiotic use. As the vast majority of the Danish pork is exported, future studies should examine consumer perceptions of antibiotic use in pig production in importing countries.
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http://dx.doi.org/10.1016/j.prevetmed.2021.105310DOI Listing
April 2021

Moral Convictions and Meat Consumption-A Comparative Study of the Animal Ethics Orientations of Consumers of Pork in Denmark, Germany, and Sweden.

Animals (Basel) 2021 Jan 28;11(2). Epub 2021 Jan 28.

Department of Food and Resource Economics, University of Copenhagen, 1958 Frederiksberg C, Denmark.

Background: The relationship between animal ethics orientations and consumer demand for meat with high standards of animal welfare, and the way this relationship plays out in different countries, is not well understood. Using pork as a case study, this comparative study aims to identify the animal ethics orientations that drive purchases of welfare meat in Denmark, Germany, and Sweden.

Methods: Cross-sectional questionnaire data from representative samples of approximately 1600 consumers in each country were collected. A segmentation of pork consumers (using latent profile analysis) was carried out.

Results: In all three countries, two subgroups were concerned about farm animal welfare: the first subgroup was driven by animal rights values; the second subgroup by animal protection values, where the main principle was that "it is all right to use animals as long as they are treated well". Other consumer groups are less concerned about farm animal welfare and display little or no preference for welfare pork.

Conclusions: In all three countries, dual demand for welfare pork exists. The findings of this study can be used, among others, to understand the marketability of enhanced welfare animal products and the potential for market-driven animal welfare improvements.
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http://dx.doi.org/10.3390/ani11020329DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7912257PMC
January 2021

Benchmarking Farm Animal Welfare-A Novel Tool for Cross-Country Comparison Applied to Pig Production and Pork Consumption.

Animals (Basel) 2020 May 31;10(6). Epub 2020 May 31.

Department of Food and Resource Economics, University of Copenhagen, Copenhagen, 1958 Frederiksberg C, Denmark.

A pluralist approach to farm animal welfare, combining animal welfare legislation with market-driven initiatives, has developed in many countries. To enable cross-country comparisons of pig welfare, a number of welfare dimensions, covering the features typically modified in legislative and market-driven welfare initiatives aimed at pig production, were defined. Five academic welfare experts valued the different welfare states within each dimension on a 0-10 scale, then assessed the relative contribution of each dimension to overall welfare on a 1-5 scale. By combining these values and weights with an inventory of pig welfare initiatives in five countries, the additional welfare generated by each initiative was calculated. Together with information on the national coverage of each initiative, the Benchmark value for each country's production and consumption of pork could be calculated on a scale from 0 to 100. Two (Sweden and the UK) had a much higher Benchmark value than the rest. However, there was a drop in the Benchmark for consumption in Sweden and the UK (indicating imports from countries with lower-Benchmark values for production). Even though the experts differed in the values and weights ascribed to different initiatives, they were largely in agreement in their ranking of the countries.
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http://dx.doi.org/10.3390/ani10060955DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7341196PMC
May 2020

Activated monocytes and markers of inflammation in newly diagnosed multiple sclerosis.

Immunol Cell Biol 2020 08 5;98(7):549-562. Epub 2020 May 5.

Department of Neurology, Aarhus University Hospital, Palle Juul-Jensens Boulevard 165, DK-8200, Aarhus N, Denmark.

In multiple sclerosis (MS), the inflammation and demyelination of the central nervous system (CNS) develop in distinct ways. This makes diagnosing patients difficult, imperative to initiating early and proper treatment. Several common features exist, among them a profound infiltration of monocytes into the CNS mediating demyelination and tissue destruction. In the periphery, monocytes are divided into three subsets depending on expression of CD14 and CD16, representing different stages of activation and differentiation. To investigate their involvement in MS, peripheral blood mononuclear cells (PBMCs) from 61 patients with incipient, untreated MS and 22 symptomatic control (SC) patients as well as 6 patients with radiologically isolated syndrome (RIS) were characterized ex vivo. In addition, paired serum and cerebrospinal fluid (CSF) samples were analyzed with a panel of biomarkers. In PBMC samples, we demonstrate decreased levels of nonclassical monocytes with a concomitant significant decrease of human endogenous retrovirus (HERV) H3 envelope epitopes on this monocyte subset compared with SC and RIS. The observed HERV expression is present on nonclassical monocytes irrespective of MS and thus presumably a result of the inflammatory activation. For the other surface markers analyzed, we found significantly decreased expression between classical and nonclassical monocytes. In matched samples of CSF a highly significant increase in levels of soluble markers of activation and inflammation is shown, and notably this is not the case for the serum samples. Of the soluble markers investigated, interleukin (IL)-12/IL-23p40 had the highest discriminatory power in differentiating patients with MS from SC and RIS, almost comparable to the immunoglobulin G index.
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http://dx.doi.org/10.1111/imcb.12337DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7496724PMC
August 2020

Costs and Benefits of Alternative Strategies to Control the Spread of Livestock-Acquired Methicillin-Resistant Staphylococcus Aureus From Pig Production.

Value Health 2020 01 9;23(1):89-95. Epub 2019 Sep 9.

Department of Food and Resource Economics, University of Copenhagen, Copenhagen, Denmark.

Background: Livestock-acquired methicillin-resistant Staphylococcus aureus (LA-MRSA) is a concern in healthcare and a political priority in some countries.

Objective: This study investigates the net societal costs of 2 alternative strategies for controlling LA-MRSA in Denmark: (1) eradicating LA-MRSA in all pig housing units, and (2) containing LA-MRSA within the units.

Methods: Benefits and costs are considered for affected economic sectors: healthcare, pig production, pig-related industries, and public administration.

Results: The cost to society of eradication is estimated at €2.3 to €2.5 billion (present value). Containment will cost €55 to €93 million. For both strategies, the main cost lies in primary pig production-for containment this is mainly due to establishing and operating anterooms and shower rooms, and for eradication it is due to production losses, loss of genetic resources, and costs of cleaning and disinfection.

Conclusion: Compared with these costs, health economic benefits are moderate for both strategies. Containment is superior to eradication when measured by a benefit-cost ratio.
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http://dx.doi.org/10.1016/j.jval.2019.07.006DOI Listing
January 2020

A taste for locally produced food - Values, opinions and sociodemographic differences among 'organic' and 'conventional' consumers.

Appetite 2020 04 28;147:104544. Epub 2019 Nov 28.

Department of Food and Resource Economics, University of Copenhagen, Rolighedsvej 25, DK-1958, Frederiksberg C, Denmark.

Local food has received considerable attention in recent years. It is seen as a response to increased demand for authentic foods, just as organic foods have been considered to be. It is unclear whether organic and local are two complementary or competitive trends in food consumption. This study addresses this question with a mixed methods investigation of why Danish consumers of organic products and conventional consumers of local products choose locally produced food, what values and opinions they associate with local food, and whether there are sociodemographic differences between the groups. The results show that the same values and opinions tended to motivate organic consumers and a group of committed conventional consumers of local foods. However, organic consumers were much more likely to include environmental issues in their deliberations. Another group of local-food consumers did not seem to be motivated by values and opinions when purchasing locally produced foods. Some sociodemographic differences between the groups were found: organic consumers were more likely to live in the capital than committed local consumers; to have a lengthy education than consumers of local foods; and committed local-food consumers were more likely than organic consumers to have a vocational education. The article concludes that while it is to some extent the same preference for authentic food that motivates organic and committed conventional local-food consumers to buy locally produced foods, it is at the same time different types of consumers who prefer (conventional) local food and organic food.
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http://dx.doi.org/10.1016/j.appet.2019.104544DOI Listing
April 2020

Diagnostic Value of Cerebrospinal Fluid Neurofilament Light Protein in Neurology: A Systematic Review and Meta-analysis.

JAMA Neurol 2019 Sep;76(9):1035-1048

Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg.

Importance: Neurofilament light protein (NfL) is elevated in cerebrospinal fluid (CSF) of a number of neurological conditions compared with healthy controls (HC) and is a candidate biomarker for neuroaxonal damage. The influence of age and sex is largely unknown, and levels across neurological disorders have not been compared systematically to date.

Objectives: To assess the associations of age, sex, and diagnosis with NfL in CSF (cNfL) and to evaluate its potential in discriminating clinically similar conditions.

Data Sources: PubMed was searched for studies published between January 1, 2006, and January 1, 2016, reporting cNfL levels (using the search terms neurofilament light and cerebrospinal fluid) in neurological or psychiatric conditions and/or in HC.

Study Selection: Studies reporting NfL levels measured in lumbar CSF using a commercially available immunoassay, as well as age and sex.

Data Extraction And Synthesis: Individual-level data were requested from study authors. Generalized linear mixed-effects models were used to estimate the fixed effects of age, sex, and diagnosis on log-transformed NfL levels, with cohort of origin modeled as a random intercept.

Main Outcome And Measure: The cNfL levels adjusted for age and sex across diagnoses.

Results: Data were collected for 10 059 individuals (mean [SD] age, 59.7 [18.8] years; 54.1% female). Thirty-five diagnoses were identified, including inflammatory diseases of the central nervous system (n = 2795), dementias and predementia stages (n = 4284), parkinsonian disorders (n = 984), and HC (n = 1332). The cNfL was elevated compared with HC in a majority of neurological conditions studied. Highest levels were observed in cognitively impaired HIV-positive individuals (iHIV), amyotrophic lateral sclerosis, frontotemporal dementia (FTD), and Huntington disease. In 33.3% of diagnoses, including HC, multiple sclerosis, Alzheimer disease (AD), and Parkinson disease (PD), cNfL was higher in men than women. The cNfL increased with age in HC and a majority of neurological conditions, although the association was strongest in HC. The cNfL overlapped in most clinically similar diagnoses except for FTD and iHIV, which segregated from other dementias, and PD, which segregated from atypical parkinsonian syndromes.

Conclusions And Relevance: These data support the use of cNfL as a biomarker of neuroaxonal damage and indicate that age-specific and sex-specific (and in some cases disease-specific) reference values may be needed. The cNfL has potential to assist the differentiation of FTD from AD and PD from atypical parkinsonian syndromes.
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http://dx.doi.org/10.1001/jamaneurol.2019.1534DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6580449PMC
September 2019

Are independent agricultural advisors more oriented towards recommending reduced pesticide use than supplier-affiliated advisors?

J Environ Manage 2019 Jul 7;242:507-514. Epub 2019 May 7.

(a)Aarhus University, Department of Environmental Science, Frederiksborgvej 399, DK-4000, Roskilde, Denmark. Electronic address:

This paper explores whether agricultural advisors employed by chemical companies or agricultural companies selling pesticides (supplier-affiliated advisors) are more likely to recommend more intensive use of pesticides than advisors employed by companies without an economic interest in selling pesticides (independent advisors). We further test whether potential differences in advice are caused by differences in advisors' perceived demands for advice from farmers, different environmental risk perceptions about pesticide use or different weighing of the purposes of pesticide use. The analysis is based on a survey administered to the whole population of 540 advisors in Denmark; we received 227 valid responses. The main finding is that pesticide advice differs across company type. We find that supplier-affiliated advisors are less likely to recommend lower doses - scoring on average 3.9 on a scale from 1 (never) to 5 (always). Independent advisors employed at Danish Agricultural Advisory Services score an average of 4.3. The difference is statistically significant. The analysis does not offer strong support for the different causal mediators we examined. Advisors across company type tend to weigh different objectives equally; tend to agree on environmental risk perception of using pesticides; and differ only slightly on perceived farmer demand. One possible conclusion, therefore, is that explanation is as simply that differences in economic incentives produce different recommendations between advisory companies. Policy implications of the findings are that the European Union should consider addressing this difference more directly when regulating the use of pesticides in European agriculture through e.g. the Sustainable Use of Pesticides Directive (Directive, 2009/128/EC). More differentiation in the approaches for informing different types of advisors might be needed. Moreover, our results point towards the need for knowledge about whether advisors in other countries than Denmark tend to believe that approved pesticides are innocuous to the environment because such perceptions might hamper initiatives to reduce the doses of approved pesticides.
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http://dx.doi.org/10.1016/j.jenvman.2019.04.091DOI Listing
July 2019

Nationwide prevalence and incidence study of neuromyelitis optica spectrum disorder in Denmark.

Neurology 2018 12 9;91(24):e2265-e2275. Epub 2018 Nov 9.

From the Department of Neurology (V.P., K.S., T.P.), Aarhus University Hospital; Department of Neurology (Z.I., H.H.N.), Odense University Hospital; Institute of Clinical Research (Z.I., H.H.N.), Institute of Molecular Biology (H.H.N.), and Department of Regional Health Research, Faculty of Health Sciences (E.S.), University of Southern Denmark, Odense; The Danish Multiple Sclerosis Center (M.M., P.E.H.J., F.S.), Department of Neurology, Rigshospitalet, University of Copenhagen; The Danish Multiple Sclerosis Registry (M.M., N.K.-H.), Department of Neurology, Rigshospitalet, Copenhagen University Hospital; Department of Clinical Epidemiology, Clinical Institute (N.K.-H.), and Department of Biomedicine (T.C.), Aarhus University; MS-Clinic of Southern Jutland (Sønderborg, Esbjerg, Kolding) (M.K., E.S.), Department of Neurology, Hospital of Southern Jutland, Sønderborg; Department of Neurology (C.C.P., Z.M.), Aalborg University Hospital; Multiple Sclerosis Unit (S.F.R.), Department of Neurology, Herlev Hospital, Copenhagen; Department of Neurology (M.B.J.), Nordsjællands Hospital, Hillerød; Department of Neurology (A.E.P.), Hospital of Southwest Jutland, Esbjerg; Department of Neurology (L.R.), Hospital of Central Denmark Region, Viborg; Department of Autoimmunology and Biomarkers (M.C.L., N.H.), Statens Serum Institut, Copenhagen; and Department of Neurology (J.L.F.), Rigshospitalet Glostrup, Faculty of Health and Medical Sciences, University of Copenhagen, Glostrup, Denmark.

Objectives: To estimate the nationwide population-based incidence, prevalence, and geographical distribution of neuromyelitis optica (NMO) spectrum disorder (NMOSD) in Denmark based on the 2015 International Panel for NMO Diagnosis (IPND) criteria.

Methods: We conducted a multicentre, historically prospective study. Data were sourced from the Danish National Patient Registry, the Danish Multiple Sclerosis Registry, departments of neurology, and laboratories providing aquaporin-4 antibody test. Cases were selected based on the 2006 Wingerchuk and the 2015 IPND criteria and were individually validated by an expert panel.

Results: We confirmed NMO in 30 cases (2006 criteria) and NMOSD in 56 cases (2015 IPND criteria) between 2007 and 2014. Defined by the 2006 criteria, the incidence of NMO was 0.029 per 100,000 person-years (95% confidence interval [CI] 0.014-0.051), and the prevalence (aged 16 years and older) was 0.566 per 100,000 (95% CI 0.370-0.830). Based on the 2015 IPND criteria, the incidence of NMOSD was 0.070 per 100,000 person-years (95% CI 0.046-0.102), and the prevalence (aged 16 years and older) was 1.09 per 100,000 (95% CI 0.808-1.440), without regional differences.

Conclusions: Our estimates of incidence and prevalence are similar to other Caucasian population-based studies using the 2015 IPND criteria. We found no geographical clustering in Denmark.
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http://dx.doi.org/10.1212/WNL.0000000000006645DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6329324PMC
December 2018

Cerebrospinal fluid free kappa light chains and kappa index perform equal to oligoclonal bands in the diagnosis of multiple sclerosis.

Clin Chem Lab Med 2018 12;57(2):210-220

Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus N, Denmark.

Background Detection of intrathecal immunoglobulin G (IgG) synthesis by gold standard oligoclonal bands (OCB) or IgG index remains an integral part of multiple sclerosis (MS) diagnostics, although both methods have weaknesses. Emerging evidence suggests that automated detection of free light chains (FLC) in the cerebrospinal fluid (CSF) has diagnostic performance equal to OCB. The objective of this study was to compare the diagnostic performance of CSF FLC with OCB and IgG index in a large cohort of Scandinavian patients referred for MS evaluation. Methods We prospectively included 230 patients suspected for MS. They are composed of patients with MS (n=96), clinically isolated syndrome (n=37), other neurological diseases (OND, n=31) and symptomatic controls (SC, n=66). CSF and serum samples were analyzed for kappa and lambda FLC, OCB and IgG index. Diagnostic performance was evaluated by receiver operating characteristic (ROC) analysis. Results Both the absolute concentration of CSF-kappa and the kappa index had excellent MS diagnostic performances with ROC area under the curve of 0.93 and 0.94 (MS vs. SC+OND). At the 0.42 mg/L cutoff, CSF-kappa had sensitivity and specificity of 93.8% and 85.6%, whereas sensitivity and specificity for OCB was 82.3% and 93.8% (72.9% and 95.9% for IgG index at cutoff 0.64). CSF-lambda and lambda index performed inferior to CSF-kappa and kappa index. Conclusions CSF-kappa and kappa index represent automated, rapid and low-cost alternatives to OCB. Using merely the absolute concentration of CSF-kappa is a logistic advantage in the clinical laboratories.
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http://dx.doi.org/10.1515/cclm-2018-0400DOI Listing
December 2018

A phase II baseline versus treatment study to determine the efficacy of raltegravir (Isentress) in preventing progression of relapsing remitting multiple sclerosis as determined by gadolinium-enhanced MRI: The INSPIRE study.

Mult Scler Relat Disord 2018 Aug 28;24:123-128. Epub 2018 Jun 28.

Neuroscience and Trauma, Queen Mary University of London, Blizard Institute, Barts and the London School of Medicine and Dentistry, United Kingdom.

Background: Although the aetiology of multiple sclerosis (MS) remains elusive, it is clear that Epstein Barr virus (EBV) and possibly other viruses play a role in the pathogenesis of MS. Laboratory evidence suggests that human endogenous retroviruses (HERVs) could also have a role, but no interventional therapy has determined what will happen if HERVs are suppressed. Recent epidemiological evidence indicates patients with HIV infection have a significantly lower risk of developing MS and that HIV antiretroviral therapies may be coincidentally inhibiting HERVs, or other retroelements, that could be implicated in MS.

Objectives: To systematically investigate the effects of an HIV integrase strand inhibitor, raltegravir, on the number of gadolinium (Gd)-enhanced MRI lesions in people with active relapsing MS.

Methods: This is a Phase 2a clinical trial where twenty participants were enrolled in a 3 month baseline phase followed by 3 months of treatment with raltegravir 400 mg twice a day. Patients had monthly Gd-enhanced MRI, saliva collection to test for EBV shedding, blood sampling for safety monitoring, virology (including HERVs), measurement of immunological and inflammatory markers; and physical, neurological and quality-of-life assessments.

Results: All patients completed the six months trial period.The primary outcome measure of MS disease activity was the number of Gd-enhancing lesions observed, and raltegravir had no significant effect on the rate of development of Gd-enhancing lesions during the treatment phase compared with the baseline phase. Additionally, there was no change in secondary outcomes of either disability or quality-of-life measures that could reasonably be attributed to the intervention. There was a significant positive between HERV-W/MSRV (multiple sclerosis related virus) Gag Flix (Fluorescence index) B cells and the number of Gd-enhanced lesions at any visit (p = 0.029), which was independent of any potential influence of the trial drug administration. Regarding EBV shedding, there was no significant correlation between the amount of EBV shedding and the number of lesions. No change was detected in inflammatory markers (IL-8, IL-1β, IL-6, IL-10, TNF, IL-12p70 and HCRP), which were all within normal limits both before and after the intervention. Serum CD163 expression was also unchanged by raltegravir.

Conclusions: Raltegravir did not have any impact on MS disease activity. This could be due to the choice of antiretroviral agent used in this study, the need for a combination of agents, as used in treating HIV infection, the short treatment period or dosing regimen, or the lack of a role of HERV expression in MS once the disease is established. Borderline significance for the association between EBV shedding and the total number of lesions, probably driven by new lesion development, may indicate EBV shedding as a marker of inflammatory disease activity. In conclusion, interesting correlations between HERV-W markers, EBV shedding and new MRI lesions, independent from treatment effects, were found.
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http://dx.doi.org/10.1016/j.msard.2018.06.002DOI Listing
August 2018

Time to steroid treatment in severe acute optic neuritis.

Brain Behav 2018 08 22;8(8):e01032. Epub 2018 Jun 22.

Department of Ophthalmology, Aarhus University Hospital, Aarhus, Denmark.

Objectives: Steroid treatment can accelerate visual recovery in patients with optic neuritis (ON), but it is unknown whether the timing of the start of treatment influences the outcome. The main purpose of this observational study was to assess the effect of early onset steroid treatment of ON on visual prognosis and retinal morphology.

Methods: Forty-nine patients with acute mild/moderate (n = 21) or severe (n = 28) ON, and an equal number of healthy controls were enrolled. Patients with severe ON either received early onset steroid treatment (initiated within 1 week of presentation with visual loss) (n = 9), late-onset treatment (initiated after 1 week) (n = 13), or no treatment (n = 6). Visual function and retinal morphology was studied after 6 and 12 months.

Results: All measures of visual function had improved after 6 months (p ≤ 0.03) in the three groups with severe ON. This was not the case for Rayleigh match setting range (SR) in the nontreated group (p = 0.24), or for SR (p = 0.08) and latency to P100 of visual evoked potential (p = 0.08) in the late-onset treated group. After 12 months, further improvement occurred in the nontreated and late-treated groups, but not in the early treated group. Macular retinal nerve fiber layer (mRNFL) and ganglion cell plus inner plexiform layer had decreased significantly (p ≤ 0.001) in all three groups with severe ON after 6 months. After 12 months, only mRNFL had further significantly decreased and only in the late-onset treated group (p = 0.02).

Conclusion: The beneficial effects of early onset steroid treatment of ON is limited to a few months whereas the long-term prognosis is independent of the timing of treatment.
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http://dx.doi.org/10.1002/brb3.1032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6085902PMC
August 2018

Subsets of activated monocytes and markers of inflammation in incipient and progressed multiple sclerosis.

Immunol Cell Biol 2018 02 11;96(2):160-174. Epub 2017 Dec 11.

Department of Biomedicine, Aarhus University, Bartholin Building, Wilhelm Meyers Allé 4, DK-8000, Aarhus C, Denmark.

Multiple sclerosis (MS) is an immune mediated, inflammatory and demyelinating disease of the central nervous system (CNS). Substantial evidence points toward monocytes and macrophages playing prominent roles early in disease, mediating both pro- and anti-inflammatory responses. Monocytes are subdivided into three subsets depending on the expression of CD14 and CD16, representing different stages of inflammatory activation. To investigate their involvement in MS, peripheral blood mononuclear cells from 40 patients with incipient or progressed MS and 20 healthy controls were characterized ex vivo. In MS samples, we demonstrate a highly significant increase in nonclassical monocytes (CD14+CD16++), with a concomitant significant reduction in classical monocytes (CD14++CD16-) compared with healthy controls. Also, a significant reduction in the surface expression of CD40, CD163, and CD192 was found, attributable to the upregulation of the nonclassical monocytes. In addition, significantly increased levels of human endogenous retrovirus (HERV) envelope (Env) epitopes, encoded by both HERV-H/F and HERV-W, were specifically found on nonclassical monocytes from patients with MS; emphasizing their involvement in MS disease. In parallel, serum and cerebrospinal fluid (CSF) samples were analyzed for soluble biomarkers of inflammation and neurodegeneration. For sCD163 versus CD163, no significant correlations were found, whereas highly significant correlations between levels of soluble neopterine and the intermediate monocyte (CD14++CD16+) population was found, as were correlations between levels of soluble osteopontin and the HERV Env expression on nonclassical monocytes. The results from this study emphasize the relevance of further focus on monocyte subsets, particularly the nonclassical monocytes in monitoring of inflammatory diseases.
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http://dx.doi.org/10.1111/imcb.1025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5836924PMC
February 2018

Retroviral envelope proteins: Involvement in neuropathogenesis.

J Neurol Sci 2017 Sep 22;380:151-163. Epub 2017 Jul 22.

Department of Biomedicine, Aarhus University, Bartholin Building, Wilhelm Meyers Allé 4, DK-8000 Aarhus C, Denmark. Electronic address:

The primary disease caused by infection with the exogenous human retroviruses, human immunodeficiency virus 1 (HIV-1) or human T-cell lymphotropic virus 1 (HTLV-1), may overlay manifestations of additional autoimmune pathogenesis. Currently, a role for human endogenous retroviruses (HERVs) is also emerging in some autoimmune/immune-mediated diseases, particularly in multiple sclerosis (MS). Both exogenous and endogenous retroviruses have the potential to elicit the processes leading to autoimmune disease. The pathogenicity of the retroviral envelope protein (Env) is a key player with notable importance in neuroimmune diseases. An essential prerequisite of retroviral infection is the interactions between Env (the retroviral adhesion) proteins on the virion and specific surface receptors on the host cell. These interactions facilitate fusion of the viral envelope and cellular membranes. Additional fusiogenic activities mediated by Env may be beneficial (establishment of the syncytiotrophoblast induced by a HERV-encoded Env) or detrimental to the host (syncytia formation, induction of apoptosis), and Envs are further implied in the direct induction of proinflammatory cytokines, the regulation of autophagy, and pathways of cell death. The pathogenic potential of retroviral Env is therefore not limited to the pathogenetics of infection but also comprise the pathogenic/toxic capacity of the Env protein itself.
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http://dx.doi.org/10.1016/j.jns.2017.07.027DOI Listing
September 2017

Consumer preferences for pig welfare - Can the market accommodate more than one level of welfare pork?

Meat Sci 2017 Jul 22;129:140-146. Epub 2017 Feb 22.

Department of Food and Resource Economics, University of Copenhagen, Rolighedsvej 25, 1958 Frederiksberg C, Denmark.

The purpose of the present paper is to investigate the market potential of pork labelled to indicate medium and high levels of animal welfare. The paper asks, in particular, whether there is a risk that Danish consumers will abandon high level welfare pork if less expensive products with a medium level of animal welfare became available. The study was based on an online questionnaire with a choice experiment involving 396 Danish respondents. The results indicated that the Danish market could accommodate more than one pork product with a welfare label but the price differential separating medium and high level animal welfare pork will have to be quite narrow. In addition, full willingness-to-pay of consumers who want to buy high level welfare pork cannot be relied upon to incentivise new consumers to buy medium welfare pork. Further, raising brand awareness in the shopping situation and improving consumer's understanding of brand attributes for high level welfare brands were found to be vital.
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http://dx.doi.org/10.1016/j.meatsci.2017.02.018DOI Listing
July 2017

A multi-biomarker follow-up study of patients with multiple sclerosis.

Brain Behav 2016 09 11;6(9):e00509. Epub 2016 Jul 11.

Department of Neurology Aarhus University Hospital Nørrebrogade 44 DK-8000 Aarhus C Denmark.

Objectives: This study aimed to examine the levels of the macrophage marker sCD163 and other biomarkers at the time of diagnosis of patients with either clinically isolated syndrome (CIS) or relapsing-remitting multiple sclerosis (RRMS), and assess relation to clinical indicators of prognosis, disease activity (DA), and changes in the levels of these biomarkers at follow-up.

Materials And Methods: The clinical status and MRI were reevaluated in 56 patients more than 1 year after diagnosis with a median follow-up time of 2 years. Levels of biomarkers in serum and cerebrospinal fluid (CSF) samples were evaluated by enzyme-linked immunosorbent assays.

Results: There was no significant difference in time to DA between patients with CIS and RRMS. A high sCD163 ratio (>0.07) was significantly ( = 0.04) associated with time to DA in the untreated patient group. In 21 patients reevaluated with serum and CSF samples, the sCD163 ratio levels decreased from 0.068 to 0.054 ( = 0.026) in the CIS/RRMS-treated group. The CSF CXCL13, CXCL13 ratio, CSF neurofilament light polypeptide and osteopontin levels also decreased significantly in the CIS/RRMS-treated group.

Conclusions: The levels of all biomarkers changed concurrently with MS treatment. The sCD163 ratio was identified as a potential novel marker for time to DA.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5036432PMC
http://dx.doi.org/10.1002/brb3.509DOI Listing
September 2016

The costs of preventive activities for exotic contagious diseases-A Danish case study of foot and mouth disease and swine fever.

Prev Vet Med 2016 Sep 19;131:111-120. Epub 2016 Jul 19.

Department of Food and Resource Economics, University of Copenhagen, Rolighedsvej 25, 1958 Frederiksberg C, Denmark. Electronic address:

The present paper provides an overview of the costs of preventive activities, currently undertaken in Denmark, related to foot and mouth disease (FMD) and classical and African swine fever (SF). Only costs held between outbreaks were included. Costs were divided into public costs and costs paid by the pig and cattle industries, respectively. Data were retrieved from multiple sources such as databases, legal documents, official statistics, yearly reports and expert opinions. As no previous studies have assessed such costs, data collection and estimation procedures were discussed and decided upon in a group of experts from universities, industry, and public authorities. The costs of each preventive activity were related to the type of activity, the number of times the activity was carried out and the share of costs that could be associated with FMD or SF. Uncertainty about parameters was incorporated in the analysis by assuming that the FMD/SF shares of costs as well as total costs for each activity could take on a most likely as well as a minimum and maximum value. A high degree of transparency was prioritized in the cost analysis, which enables reproducibility and easy access to conducting sensitivity analyses. A total of 27 FMD/SF preventive activities were identified. The estimated median (minimum-maximum) of total costs amounted to €32 (18-50) million in 2013. The single most costly FMD/SF related activity, amounting to €8 (5-13) million or 26% of total costs, was a national legal requirement to clean lorries immediately after transportation of live animals. The distribution of costs between stakeholders was estimated to be as follows: pig industry 63%, cattle industry 27%, and the public authorities 10%. Most of the activities focused on reducing the probability of spreading FMD/SF, while only a few activities were directed mainly towards reducing the probability of introduction. Legally required FMD/SF activities (mainly based on EU legislation) accounted for 60% of the activities, while FMD/SF related measures agreed on at sector level and measures implemented due to individual initiatives, such as farmer's investment in specially built delivery facilities, each accounted for 20%.
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http://dx.doi.org/10.1016/j.prevetmed.2016.07.010DOI Listing
September 2016

Human endogenous retroviruses in neurologic disease.

Authors:
Tove Christensen

APMIS 2016 Jan-Feb;124(1-2):116-26

Department of Biomedicine, Aarhus University, Aarhus C, Denmark.

Endogenous retroviruses are pathogenic - in other species than the human. Disease associations for Human Endogenous RetroViruses (HERVs) are emerging, but so far an unequivocal pathogenetic cause-effect relationship has not been established. A role for HERVs has been proposed in neurological and neuropsychiatric diseases as diverse as multiple sclerosis (MS) and schizophrenia (SCZ). Particularly for MS, many aspects of the activation and involvement of specific HERV families (HERV-H/F and HERV-W/MSRV) have been reported, both for cells in the circulation and in the central nervous system. Notably envelope genes and their gene products (Envs) appear strongly associated with the disease. For SCZ, for ALS, and for HIV-associated dementia (HAD), indications are accumulating for involvement of the HERV-K family, and also HERV-H/F and/or HERV-W. Activation is reasonably a prerequisite for causality as most HERV sequences remain quiescent in non-pathological conditions, so the importance of regulatory pathways and epigenetics involved in regulating HERV activation, derepression, and also involvement of retroviral restriction factors, is emerging. HERV-directed antiretrovirals have potential as novel therapeutic paradigms in neurologic disease, particularly in MS. The possible protective or ameliorative effects of antiretroviral therapy in MS are substantiated by reports that treatment of HIV infection may be associated with a significantly decreased risk of MS. Further studies of HERVs, their role in neurologic diseases, and their potential as therapeutic targets are essential.
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http://dx.doi.org/10.1111/apm.12486DOI Listing
June 2016

Biomarkers of inflammation and axonal degeneration/damage in patients with newly diagnosed multiple sclerosis: contributions of the soluble CD163 CSF/serum ratio to a biomarker panel.

PLoS One 2015 10;10(4):e0119681. Epub 2015 Apr 10.

Department of Biomedicine, Bartholin Building, Wilhelm Meyers Allé 4, Aarhus University, DK-8000 Aarhus C, Denmark.

Background: Expression of soluble CD163 (sCD163), a macrophage/microglia biomarker, is increased in inflammatory conditions, and sCD163 levels in the cerebrospinal fluid (CSF) have recently been shown to be elevated in patients with multiple sclerosis (MS): the sCD163 CSF/serum ratio was elevated in patients with relapsing-remitting MS (RRMS), primary progressive MS (PPMS), and clinically isolated syndrome (CIS) compared with symptomatic controls.

Objective: To investigate the contributions of the sCD163 CSF/serum ratio to a biomarker panel focusing on inflammation and axonal degeneration in newly diagnosed MS; thus optimising a diagnostic biomarker panel for MS.

Methods: After a full MS diagnostic work-up, including collection of paired samples of CSF and serum, 125 patients were included in this study. Patients were divided into groups based on their diagnosis, and patients with normal clinical and paraclinical findings were defined as symptomatic controls. Serum and CSF levels, ratios, and indices of sCD163, CXCL13, osteopontin, neopterin, and CSF levels of neurofilament light polypeptide were determined by enzyme-linked immunosorbent assays (ELISAs). For sCD163 the results constitute a post-hoc analysis of already published data.

Results: All tested biomarkers, notably the sCD163 ratio, the CXCL13 ratio, the NEO ratio, the CSF level of NfL, the IgG index, and the serum level of OPN, were significantly correlated to RRMS, PPMS, and/or CIS. The individual biomarkers in single tests had a lower performance than the IgG index, however, their combined receiver operating characteristic (ROC) curve demonstrated excellent diagnostic discriminatory power.

Conclusion: The biomarker panel showed distinct profiles for each patient group and could be a valuable tool for clinical differentiation of MS subgroups. The combined ROC analysis showed that sCD163 contributes positively as a diagnostic marker to a panel of established MS biomarkers. Patients with PPMS were demonstrated to have significantly elevated levels of both inflammatory and degenerative markers.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0119681PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4393241PMC
April 2016

Improvement in reading symptoms following botulinum toxin A injection for convergence insufficiency type intermittent exotropia.

Acta Ophthalmol 2015 Aug 17;93(5):e391-2. Epub 2014 Dec 17.

Department of Ophthalmology, Glostrup Hospital, University of Copenhagen, Copenhagen, Denmark.

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http://dx.doi.org/10.1111/aos.12625DOI Listing
August 2015

Soluble CD163 as a marker of macrophage activity in newly diagnosed patients with multiple sclerosis.

PLoS One 2014 2;9(6):e98588. Epub 2014 Jun 2.

Department of Neurology, Aarhus University Hospital, Aarhus C, Denmark.

Background: Soluble CD163 (sCD163) is a macrophage specific protein known to be up-regulated in serum from patients with multiple sclerosis (MS).

Objective: To investigate sCD163 in serum and CSF (cerebrospinal fluid) from patients undergoing MS diagnostic work-up and analyse its potential as a diagnostic biomarker.

Methods: After a full MS diagnostic work-up, including collection of paired samples of CSF and serum, 183 patients were evaluated for inclusion in this study. Patients were divided into groups based on their diagnosis. Patients with normal clinical and paraclinical findings were grouped as symptomatic controls. Serum and CSF levels of sCD163 were determined by enzyme-linked immunosorbent assay (ELISA).

Results: sCD163 could be measured in all serum and CSF samples. A high sCD163 CSF/serum ratio in relation to molecular weight was found, strongly indicating local production in the CNS. Median levels of sCD163 were significantly decreased in serum and significantly elevated in CSF in patients with relapsing-remitting, and primary-progressive MS. There were, however, some overlaps of the measures between groups. In a receiver operating characteristic (ROC) analysis sCD163 CSF/serum ratio had an area under the curve of 0.72.

Conclusion: The sCD163 CSF/serum ratio was significantly increased in patients with MS and may reflect macrophage activation in MS lesions. These results suggest that primary progressive MS also is driven by inflammation in which the innate immune system plays a pivotal role.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0098588PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4041861PMC
January 2015

HERVs: have we been here before?

Mult Scler 2013 May;19(6):827-9

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http://dx.doi.org/10.1177/1352458513485051DOI Listing
May 2013

The Prospect of Market-Driven Improvements in Animal Welfare: Lessons from the Case of Grass Milk in Denmark.

Animals (Basel) 2013 Jun 4;3(2):499-512. Epub 2013 Jun 4.

Department of Food and Resource Economics, University of Copenhagen, Rolighedsvej 25, DK-1958 Frederiksberg, Denmark.

Citizens in many European countries urge that the welfare of farm animals should be improved. Policy-makers propose that this could, at least to some extent, be achieved through increased consumption of animal products produced under labeling schemes guaranteeing higher standards of animal welfare. Yet considerable uncertainties exist about the ability of the market to promote animal welfare. So far the consumption of most welfare-friendly products has been limited, and the impact of driving and limiting factors is poorly understood. Reviewing market studies, we identify the factors that have shaped the relatively successful market for grass milk in Denmark. We conclude that the positive drivers such as an appealing animal welfare attribute and animal welfare being bundled with other qualities are essentially the same as those operating in connection with less successful animal welfare-friendly products. It is therefore to be expected that other animal welfare-friendly food products marketed via "natural behaviors" in the farm animals will catch the interest of consumers. However, grass milk consumption has been supported by proper labeling, ready availability and low price premiums as well as multifaceted public support. This suggests that successful cases require the joint presence of a number of positive drivers as well as low consumption barriers.
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http://dx.doi.org/10.3390/ani3020499DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4494390PMC
June 2013

HERVs: have we been here before?

Mult Scler 2012 Dec;18(12):1670-2

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http://dx.doi.org/10.1177/1352458512469331DOI Listing
December 2012

Citrullination of histone H3 interferes with HP1-mediated transcriptional repression.

PLoS Genet 2012 Sep 13;8(9):e1002934. Epub 2012 Sep 13.

Département de Biologie du Développement, Institut Pasteur, CNRS URA2578, Unité de Régulation Epigénétique, Paris, France.

Multiple Sclerosis (MS) is an autoimmune disease associated with abnormal expression of a subset of cytokines, resulting in inappropriate T-lymphocyte activation and uncontrolled immune response. A key issue in the field is the need to understand why these cytokines are transcriptionally activated in the patients. Here, we have examined several transcription units subject to pathological reactivation in MS, including the TNFα and IL8 cytokine genes and also several Human Endogenous RetroViruses (HERVs). We find that both the immune genes and the HERVs require the heterochromatin protein HP1α for their transcriptional repression. We further show that the Peptidylarginine Deiminase 4 (PADI4), an enzyme with a suspected role in MS, weakens the binding of HP1α to tri-methylated histone H3 lysine 9 by citrullinating histone H3 arginine 8. The resulting de-repression of both cytokines and HERVs can be reversed with the PADI-inhibitor Cl-amidine. Finally, we show that in peripheral blood mononuclear cells (PBMCs) from MS patients, the promoters of TNFα, and several HERVs share a deficit in HP1α recruitment and an augmented accumulation of histone H3 with a double citrulline 8 tri-methyl lysine 9 modifications. Thus, our study provides compelling evidence that HP1α and PADI4 are regulators of both immune genes and HERVs, and that multiple events of transcriptional reactivation in MS patients can be explained by the deficiency of a single mechanism of gene silencing.
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http://dx.doi.org/10.1371/journal.pgen.1002934DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3441713PMC
September 2012

Effects of interferon-beta therapy on elements in the antiviral immune response towards the human herpesviruses EBV, HSV, and VZV, and to the human endogenous retroviruses HERV-H and HERV-W in multiple sclerosis.

J Neuroimmunol 2012 Aug 16;249(1-2):105-8. Epub 2012 May 16.

Department of Neurology, Aarhus University Hospital, Nørrebrogade 44, Aarhus C, Denmark.

Effects of treatment of multiple sclerosis patients with IFN-β on elements of the antiviral immune response to herpesviruses were analysed in a longitudinal study. We found significantly increased seroreactivity to EBV EBNA-1, and to VZV, in patients who did not respond to IFN-β therapy. We found no significant changes in seroreactivity to EBV EA, or to HSV. For the same patient cohort, we have previously demonstrated significant decreases in seroreactivities to envelope antigens for the two human endogenous retroviruses HERV-H and HERV-W, closely linked to efficacy of therapy. We further searched for correlations between seroreactivities to EBV, HSV, and VZV, and levels of mannan-binding lectin (MBL), and MBL-associated serine protease 3. We found no such correlations. Our results are in accord with recent reports of increased seroreactivity to EBV EBNA-1, and to VZV in active MS, and they support that the herpesviruses EBV and VZV together with HERV-H/HERV-W and the antiviral immune response may play a role in MS development.
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http://dx.doi.org/10.1016/j.jneuroim.2012.04.013DOI Listing
August 2012
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