| 131. |
- Song, Jie, et al.
(författare)
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Similar familial risk in multiple sclerosis subgroups
- 2017
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Ingår i: Multiple Sclerosis. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 1352-4585 .- 1477-0970.
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Tidskriftsartikel (refereegranskat)abstract
- Background: A subgroup of patients diagnosed with multiple sclerosis (MS) present with no oligoclonal bands (OCB) in the cerebrospinal fluid (CSF). Several studies report different clinical characteristics and genetic associations between the two groups. Objective: To investigate whether the OCB negative subgroup has a distinct etiology from band positive MS. Methods: Using nationwide registers to estimate familial risks, which reflect the genetic contribution of a disease. Results: Odds ratios of MS were similar for relatives to band positive and negative patients. Conclusion: From the perspective of familial liability, MS without OCB is etiologically closely related to the dominant subgroup of OCB positive MS.
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| 132. |
- Stenberg, Erik, 1979-, et al.
(författare)
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Bariatric and metabolic surgery in patients with morbid obesity and multiple sclerosis : a nationwide, matched cohort study
- 2021
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Ingår i: Surgery for Obesity and Related Diseases. - : Elsevier. - 1550-7289 .- 1878-7533. ; 17:6, s. 1108-1114
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Despite an association between obesity and multiple sclerosis (MS), very little is known regarding the safety and efficacy outcomes for patients with MS and severe obesity undergoing metabolic surgery.OBJECTIVES: The aim of the present study was to evaluate early complications and efficacy outcomes of metabolic surgery in patients with severe obesity and MS.SETTING: Nationwide, Sweden.METHODS: In this, matched cohort study, 196 patients with an MS diagnosis in the Swedish MS register who were undergoing metabolic surgery (gastric bypass or sleeve gastrectomy) with a registration in the Scandinavian Obesity Surgery Registry (SOReg) were matched 1:10 with a control group without MS diagnosis from the SOReg. A 2-stage matching procedure was used (exact match by surgical method, followed by propensity Score matching, including age, sex, preoperative BMI, surgical center, surgical access, year of surgery, hypertension, diabetes, sleep apnea, and dyslipidemia).RESULTS: Weight loss at 2 years after surgery was similar for patients with MS and controls (total weight loss 31.6 ± 9.1 versus 31.8 ± 9.2, P = .735). No significant differences were seen in either the overall postoperative complication rate (7.9% versus 7.2%, P = .778), or serious postoperative complications (3.7% versus 2.8%, P = .430). All aspects of health-related quality of life (HRQoL) improved in both groups but less so for the physical aspects of HRQoL in patients with MS.CONCLUSION: Metabolic surgery is a safe and efficient treatment for severe obesity in patients with MS, and it leads to subsequent improvements in HRQoL. Further studies addressing the effects of metabolic surgery on MS-related symptoms are needed.
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| 133. |
- Strand, Magnus, 1974-
(författare)
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Estrogen signaling in stroke : genetic and experimental studies
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Stroke is a common and multifactorial disease influenced by genetic and environmental risk factors. It is a highly heterogeneous entity consisting of two main types, ischemic (80%) and hemorrhagic (20%) stroke. The most common form of hemorrhagic stroke is intracerebral hemorrhage (ICH). Ischemic stroke mainly results from thrombotic or embolic events, while ICH is caused by the rupture of an artery in the brain.The mean age of first-ever stroke is 75 years (73 vs. 78 years, for men and women, respectively) and the age-specific stroke incidence is higher for men as compared to women, suggesting that hormonal factors confer protection. A large body of experimental and observational studies shows that estrogens exert beneficial effects in the cardiovascular system. However, large, recent, clinical randomized trials have failed to demonstrate a lower risk of stroke with hormone replacement therapy (HRT) in elderly postmenopausal women. It is possible that HRT may only protect a subgroup of women. Here, genetic predisposition might be involved. Stroke incidence is 50% higher in northern compared to southern Sweden, suggesting a genetic predisposition in this population. This relatively homogeneous population displays founder effects, making it well suited for genetic studies. Since 1985, the MONICA and VIP projects have conducted large-scale cardiovascular health surveys in this population. Information about conventional stroke risk determinants and also DNA have been collected, and two prospective, nested case-referent cohorts (113 cases and 226 controls; 275 cases and 549 controls) have been sampled.To investigate whether genes of the estrogen signaling system may be important in stroke development, we performed genetic association studies, including specific functional single nucleotide polymorphisms in the genes for estrogen receptor alpha (ERα, ESR1), and its target genes osteoprotegerin (OPG, TNFRS11B) and interleukin-6 (IL-6, IL6). We found a significant association between the common c.454-397T/T genotype in ESR1 and ICH, remaining after adjustments for conventional stroke risk factors. The c.454-397T/T genotype also associated with increased systolic (SBP) and diastolic blood pressure (DBP). The combination of c.454- 397T/T and either hypertension, increased SBP, or increased DBP boosted this association substantially and significant synergistic effects on ICH risk between this genotype and increased blood pressure were demonstrated. In a second study, we found a similar association between the common OPG-1181C/C genotype and ICH.Cognitive impairments, including spatial memory and learning deficiencies, are common after stroke. Estrogens improve cognitive functions, including memory and learning processes, in postmenopausal women and ovariectomized rodents. Post-ischemic housing of rats in an enriched environment (EE) improves recovery of spatial memory and learning impairments. Both estrogen and EE induce neuroplasticity in the hippocampus. We hypothesized that 17β- estradiol combined with EE would accelerate recovery after experimental focal brain ischemia in ovariectomized rats and that such improvements could be related to expression of nerve growth factor-induced gene A (NGFI-A) in the hippocampus. Five to six weeks after middle cerebral artery occlusion, 17β-estradiol–treated rats housed in an EE showed significant improvements in cognitive function (i.e., shorter latency and path in the Morris water maze task) and significantly higher NGFI-A mRNA expression in bilateral cornu ammonis 1 (CA1) and ipsilateral dentate gyrus (DG) compared to placebo-treated animals in EE.In conclusion, we present evidence for the association between polymorphic variants in the ESR1 and TNFRS11B genes and ICH and show that 17β-estradiol in combination with EE accelerates cognitive functions in a rat stroke model, putatively through upregulation of NGFI-A in hippocampal subregions. These findings may contribute to an increased understanding of the underlying genetic etiology of ICH and may be informative for the primary prevention of this disease. They also provide hope for 17β-estradiol combined with early environmental enrichment as a novel therapeutic option following ischemic stroke.
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| 134. |
- Sundqvist, Emilie, et al.
(författare)
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Lack of replication of interaction between EBNA1 IgG and smoking in risk for multiple sclerosis
- 2012
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Ingår i: Neurology. - 0028-3878 .- 1526-632X. ; 79:13, s. 1363-1368
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Tidskriftsartikel (refereegranskat)abstract
- Background: Epstein-Barr virus infection, smoking, HLA-A*02, and DRB1*15 have all been proposed as risk factors for multiple sclerosis (MS). In 2010, Simon et al. described an interaction on the multiplicative scale between EBNA1 immunoglobulin G (IgG) and smoking regarding risk of MS, a finding that we attempted to replicate. Methods: This Swedish case-control study consisted of patients with newly diagnosed MS and matched controls. Using logistic regression, we analyzed association to MS risk and interactions between EBNA1 IgG and smoking, HLA-DRB1*15, and A*02, respectively, on the multiplicative scale. In addition, we analyzed interactions on the additive scale using attributable proportion due to interaction (AP). Results: We did not observe any interaction on the multiplicative scale between EBNA1 IgG and any of the 3 risk factors, smoking, DRB1*15, or absence of A*02, although in a conditional analysis the interaction with absence of A*02 becomes significant. However, we observed interactions on the additive scale between EBNA1 IgG and DRB1*15 (AP = 0.34, 95% confidence interval 0.11-0.57, p = 5 x 10(-3)) and between EBNA1 IgG and absence of A*02 (AP = 0.36, 0.13-0.59, p = 2 x 10(-3)) but not between smoking and DRB1*15 and EBNA1 IgG. The interaction between EBNA1 IgG and DRB1*15 was not significant in the conditional analysis. Conclusion: We did not observe any interaction between EBNA1 IgG and smoking, regardless of scale used, and thus did not replicate the observations from Simon et al. Neurology (R) 2012;79:1363-1368
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| 135. |
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| 136. |
- Swanberg, Maria, et al.
(författare)
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MHC2TA is associated with differential MHC molecule expression and susceptibility to rheumatoid arthritis, multiple sclerosis and myocardial infarction
- 2005
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 37:5, s. 486-494
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Tidskriftsartikel (refereegranskat)abstract
- Antigen presentation to T cells by MHC molecules is essential for adaptive immune responses. To determine the exact position of a gene affecting expression of MHC molecules, we finely mapped a previously defined rat quantitative trait locus regulating MHC class II on microglia in an advanced intercross line. We identified a small interval including the gene MHC class II transactivator (Mhc2ta) and, using a map over six inbred strains combined with gene sequencing and expression analysis, two conserved Mhc2ta haplotypes segregating with MHC class II levels. In humans, a -168A --> G polymorphism in the type III promoter of the MHC class II transactivator (MHC2TA) was associated with increased susceptibility to rheumatoid arthritis, multiple sclerosis and myocardial infarction, as well as lower expression of MHC2TA after stimulation of leukocytes with interferon-gamma. We conclude that polymorphisms in Mhc2ta and MHC2TA result in differential MHC molecule expression and are associated with susceptibility to common complex diseases with inflammatory components.
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| 137. |
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| 138. |
- Teljas, Cecilia, et al.
(författare)
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Validating the diagnosis of multiple sclerosis using Swedish administrative data in Värmland County
- 2021
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Ingår i: Acta Neurologica Scandinavica. - : John Wiley & Sons. - 0001-6314 .- 1600-0404. ; 144:6, s. 680-686
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Multiple sclerosis (MS) is a chronic neurodegenerative disease of the central nervous system. Identifying MS at the population level is important for disease surveillance and allocation of resources. The Swedish National Patient Registry (NPR) has been used to study the epidemiology of MS, but the accuracy of this resource is not known. We aimed to validate a definition of MS using the Swedish NPR in Varmland County using a longitudinal cohort design.Materials and Methods: Data were extracted from the NPR, the Total Population Register, the Swedish MS Register, and medical records for the years 2001-2013. Fifteen algorithms of hospitalizations and clinic visits for MS were developed and compared with findings in medical records, which acted as the "gold standard" definition. Sensitivity, specificity, and positive and negative predictive values (PPV, NPV) were estimated.Results: Of 805 eligible persons identified in the NPR, 763 had MS (94.8%) according to medical records. Of these, 544 (71.3%) were also registered in the SMSreg. The case definition that had a well-balanced sensitivity and specificity required three or more clinic or hospital visits for MS (sensitivity of 85.3% (95% CI: 82.6-87.8) and specificity of 81.0% (95%CI: 65.9-91.4).Conclusions: Multiple case definitions with high sensitivity and moderate specificity were found, suggesting that the NPR can be used to accurately identify persons with MS.
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| 139. |
- Tengvall, Katarina, 1980-, et al.
(författare)
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Molecular mimicry between Anoctamin 2 and Epstein-Barr virus nuclear antigen 1 associates with multiple sclerosis risk
- 2019
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : NATL ACAD SCIENCES. - 0027-8424 .- 1091-6490. ; 116:34, s. 16955-16960
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Tidskriftsartikel (refereegranskat)abstract
- Multiple sclerosis (MS) is a chronic inflammatory, likely autoimmune disease of the central nervous system with a combination of genetic and environmental risk factors, among which Epstein-Barr virus (EBV) infection is a strong suspect. We have previously identified increased autoantibody levels toward the chloride-channel protein Anoctamin 2 (ANO2) in MS. Here, IgG antibody reactivity toward ANO2 and EBV nuclear antigen 1 (EBNA1) was measured using bead-based multiplex serology in plasma samples from 8,746 MS cases and 7,228 controls. We detected increased anti-ANO2 antibody levels in MS (P = 3.5 x 10(-36)) with 14.6% of cases and 7.8% of controls being ANO2 seropositive (odds ratio [OR] = 1.6; 95% confidence intervals [95% CI]: 1.5 to 1.8). The MS risk increase in ANO2-seropositive individuals was dramatic when also exposed to 3 known risk factors for MS: HLA-DRB1*15: 01 carriage, absence of HLA-A*02: 01, and high anti-EBNA1 antibody levels (OR = 24.9; 95% CI: 17.9 to 34.8). Reciprocal blocking experiments with ANO2 and EBNA1 peptides demonstrated antibody cross-reactivity, mapping to ANO2 [aa 140 to 149] and EBNA1 [aa 431 to 440]. HLA gene region was associated with anti-ANO2 antibody levels and HLADRB1*04: 01 haplotype was negatively associated with ANO2 seropositivity (OR = 0.6; 95% CI: 0.5 to 0.7). Anti-ANO2 antibody levels were not increased in patients from 3 other inflammatory disease cohorts. The HLA influence and the fact that specific IgG production usually needs T cell help provides indirect evidence for a T cell ANO2 autoreactivity in MS. We propose a hypothesis where immune reactivity toward EBNA1 through molecular mimicry with ANO2 contributes to the etiopathogenesis of MS.
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| 140. |
- Teni, Fitsum Sebsibe, et al.
(författare)
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Recent trends in disease-modifying therapy use and associated sickness absence and disability pension among people with multiple sclerosis in Sweden
- 2024
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Ingår i: MULTIPLE SCLEROSIS JOURNAL. - 1352-4585 .- 1477-0970.
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Tidskriftsartikel (refereegranskat)abstract
- Background: Disease-modifying therapies (DMTs) have led to improved health and work productivity among people with multiple sclerosis (PwMS). Objectives: To describe trajectories of recent DMT use and their association with sickness absence and/or disability pension (SADP) among PwMS in Sweden. Methods: A longitudinal register-based study was conducted among 1395 PwMS with treatment start in 2014/2015. While DMT use over 5 years was assessed using sequence analysis resulting in four clusters, a 7-year (Y-2 toY(4)) trend of SADP was analyzed using zero-inflated negative binomial regression. Results: Four clusters of DMT use trajectories were identified: long-term non-high-efficacy (483, 34.6%), long-term high-efficacy (572, 41%), escalation (221, 15.8%), and discontinuation (119, 8.5%). Progressive MS and higher expanded disability status scale scores were associated with the escalation, long-term high-efficacy, or discontinuation clusters. PwMS in the long-term high-efficacy and escalation clusters had higher likelihood of being on SADP. However, PwMS initiating high-efficacy DMTs demonstrated steeper decline in SADP than others. Conclusion: Using sequence analysis, this study showed recent DMT use trajectories among PwMS where initiation of high-efficacy DMTs has become more common. The trend of SADP was stable and lower in those using non-high-efficacy DMTs and larger improvements were shown in those initiating high-efficacy DMTs.
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