Systematic Review of Studies on Telomere Length in Patients with Multiple Sclerosis.
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ABSTRACT:
SUBMITTER: Buhring J
PROVIDER: S-EPMC8279528 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Aging is a significant factor influencing the course of multiple sclerosis (MS). Accelerated telomere attrition is an indicator of premature biological aging and a potential contributor to various chronic diseases, including neurological disorders. However, there is currently a lack of studies focusing on telomere lengths in patients with MS. We measured the average leukocyte telomere length (LTL) in biobanked DNA samples of 40 relapsing-remitting MS patients (RRMS), 20 primary progressive MS patients (PPMS), and 60 healthy controls using a multiplex quantitative polymerase chain reaction method. Changes in LTL over a period of >10 years were evaluated in a subset of 10 patients. Association analyses of baseline LTL with the long-term clinical profiles of the patients were performed using inferential statistical tests and regression models adjusted for age and sex. The cross-sectional analysis revealed that the RRMS group was characterized by a significantly shorter relative LTL, on average, as compared to the PPMS group and controls. Shorter telomeres at baseline were also associated with a higher conversion rate from RRMS to secondary progressive MS (SPMS) in the 10-year follow-up. The LTL decrease over time was similar in RRMS patients and PPMS patients in the longitudinal analysis. Our data suggest a possible contributory role of accelerated telomere shortening in the pathobiology of MS. The interplay between disease-related immune system alterations, immunosenescence, and telomere dynamics deserves further investigation. New insights into the mechanisms of disease might be obtained, e.g., by exploring the distribution of telomere lengths in specific blood cell populations.
| S-EPMC8128833 | biostudies-literature
Project description:OBJECTIVE:To assess whether biological aging as measured by leukocyte telomere length (LTL) is associated with clinical disability and brain volume loss in multiple sclerosis (MS). METHODS:Adults with MS/clinically isolated syndrome in the University of California, San Francisco EPIC cohort study were included. LTL was measured on DNA samples by quantitative polymerase chain reaction and expressed as telomere to somatic DNA (T/S) ratio. Expanded Disability Status Scale (EDSS) and 3-dimensional T1-weighted brain magnetic resonance imaging were performed at baseline and follow-up. Associations of baseline LTL with cross-sectional and longitudinal outcomes were assessed using simple and mixed effects linear regression models. A subset (n = 46) had LTL measured over time, and we assessed the association of LTL change with EDSS change with mixed effects models. RESULTS:Included were 356 women and 160 men (mean age = 43?years, median disease duration = 6?years, median EDSS = 1.5 [range = 0-7], mean T/S ratio = 0.97 [standard deviation = 0.18]). In baseline analyses adjusted for age, disease duration, and sex, for every 0.2 lower LTL, EDSS was 0.27 higher (95% confidence interval [CI] = 0.13-0.42, p?<?0.001) and brain volume was 7.4mm3 lower (95% CI = 0.10-14.7, p = 0.047). In longitudinal adjusted analyses, those with lower baseline LTL had higher EDSS and lower brain volumes over time. In adjusted analysis of the subset, LTL change was associated with EDSS change over 10?years; for every 0.2 LTL decrease, EDSS was 0.34 higher (95% CI = 0.08-0.61, p = 0.012). INTERPRETATION:Shorter telomere length was associated with disability independent of chronological age, suggesting that biological aging may contribute to neurological injury in MS. Targeting aging-related mechanisms is a potential therapeutic strategy against MS progression. ANN NEUROL 2019;86:671-682.
| S-EPMC7135931 | biostudies-literature
Project description:Cigarette smoking is a risk factor for ageing-related disease, but its association with biological ageing, indicated by telomere length, is unclear.We systematically reviewed evidence evaluating association between smoking status and telomere length. Searches were performed in MEDLINE (Ovid) and EMBASE (Ovid) databases, combining variation of keywords "smoking" and "telomere". Data was extracted for study characteristics and estimates for association between smoking and telomere length. Quality of studies was assessed with a risk of bias score, and publication bias was assessed with a funnel plot. I2 test was used to observe heterogeneity. Meta-analysis was carried out to compare mean difference in telomere length by smoking status, and a dose-response approach was carried out for pack-years of smoking and telomere length. A sensitivity analysis was carried out to examine sources of heterogeneity.A total of 84 studies were included in the review, and 30 among them were included in our meta-analysis. Potential bias was addressed in half of included studies, and there was little evidence of small study bias. Telomere length was shorter among ever smokers compared to never smokers (summary standard mean difference [SMD]: -0.11 (95% CI -0.16 to -0.07)). Similarly, shorter telomere length was found among smokers compared to non-smokers, and among current smokers compared to never or former smokers. Dose-response meta-analysis suggested an inverse trend between pack-years of smoking and telomere length. However, heterogeneity among some analyses was observed.Shorter telomeres among ever smokers compared to those who never smoked may imply mechanisms linking tobacco smoke exposure to ageing-related disease.
| S-EPMC5562268 | biostudies-other
Project description:Background Although recent genome-wide association studies have identified several genetic variants contributing to the complex aetiology of multiple sclerosis (MS), expression and functional studies are required to further understand its molecular basis. Objectives To identify genes and pathways with differential expression in MS. Design The authors conducted a systematic review of seven microarray studies, in which expression in immune cells was compared between MS patients and controls. These studies include a previously unpublished study, which is described here in detail. Results and conclusion Although in general the overlap between studies was poor, 229 genes were found to be differentially expressed in MS in at least two studies, of which 11 were in three studies and HSPA1A in four studies. After excluding the authors' unpublished experiment which may have been affected by certain confounding factors and inclusion of treated subjects, 135 genes were identified in at least two studies. The differentially expressed genes were significantly associated with several immunological pathways, including interleukin (IL)-4, IL-6, IL-17 and glucocorticoid receptor signalling pathways. 15 of the 229 loci have shown some association with MS in published genome-wide association studies (p<0.0001), including three loci with confirmed MS risk variants.
| S-EPMC3191406 | biostudies-literature
Project description:BACKGROUND:It is widely believed that females have longer telomeres than males, although results from studies have been contradictory. METHODS:We carried out a systematic review and meta-analyses to test the hypothesis that in humans, females have longer telomeres than males and that this association becomes stronger with increasing age. Searches were conducted in EMBASE and MEDLINE (by November 2009) and additional datasets were obtained from study investigators. Eligible observational studies measured telomeres for both females and males of any age, had a minimum sample size of 100 and included participants not part of a diseased group. We calculated summary estimates using random-effects meta-analyses. Heterogeneity between studies was investigated using sub-group analysis and meta-regression. RESULTS:Meta-analyses from 36 cohorts (36,230 participants) showed that on average females had longer telomeres than males (standardised difference in telomere length between females and males 0.090, 95% CI 0.015, 0.166; age-adjusted). There was little evidence that these associations varied by age group (p=1.00) or cell type (p=0.29). However, the size of this difference did vary by measurement methods, with only Southern blot but neither real-time PCR nor Flow-FISH showing a significant difference. This difference was not associated with random measurement error. CONCLUSIONS:Telomere length is longer in females than males, although this difference was not universally found in studies that did not use Southern blot methods. Further research on explanations for the methodological differences is required.
| S-EPMC4523138 | biostudies-literature
Project description:Background: Multiple sclerosis (MS) biomarker identification is important for pathogenesis research and diagnosis in routine clinical practice. Cerebrospinal fluid (CSF) and blood cytokines as potential biomarkers that can inform MS pathogenesis, diagnosis and response to treatment have been assessed in numerous studies. However, there have been no comprehensive meta-analyses to pool cytokine data and to address their diagnostic performance. We systematically reviewed literature with meta-analyses to assess the alteration levels of cytokines and chemokines in MS. Methods: We searched PubMed and Web of Science for articles published between January 1, 1990 and April 30, 2018 for this systematic review and meta-analysis. Data were extracted from 226 included studies encompassing 13,526 MS patients and 8,428 controls. Biomarker performance was rated by a random-effects meta-analysis based on the standard mean difference between cytokine concentration in patients with MS and controls, or patients before and after treatments. Results: Of the 26 CSF cytokines and 37 blood cytokines for potential differentiation between MS patients and controls, the random-effects meta-analysis showed that 13 CSF cytokines and 21 blood cytokines were significantly increased in MS patients in comparison to the controls. Interestingly, TNF-?, CXCL8, IL-15, IL-12p40, and CXCL13 were increased in both blood and CSF of MS patients. For those cytokines analyzed in at least 10 studies, differentiation between case and control was strong for CSF CXCL13, blood IL-2R, and blood IL-23; CSF CXCL8, blood IL-2, and blood IL-17 also performed well in differentiating between MS patients and controls, whereas those of CSF TNF-? and blood TNF-?, CXCL8, IL-12, IFN-? were moderate. Furthermore, CSF IL-15, CCL19, CCL11, CCL-3, and blood CCL20, IL-12p40, IL-21, IL-17F, IL-22 had large effective sizes when differentiating between MS patients and controls but had a relatively small number of studies (three to seven studies). Conclusion: Our findings clarified the circulating cytokine profile in MS, which provide targets for disease modifying treatments, and suggest that cytokines have the potential to be used as biomarkers for MS.
| S-EPMC6787166 | biostudies-literature
Project description:Accelerated telomere shortening has been associated with several age-related diseases and/or decreased lifespan in humans. The Mediterranean diet (MedDiet) is considered to be 1 of the most recognized diets for disease prevention and healthy aging, partially due to its demonstrated anti-inflammatory and antioxidative properties which may impact on telomere length (TL). The aim of this meta-analysis was to determine the associations between MedDiet adherence and TL maintenance. MEDLINE-PubMed and Cochrane databases were searched up to December 2018 for studies evaluating the association between MedDiet adherence and TL in blood cells. Two reviewers, working independently, screened all titles and abstracts to identify studies that met the inclusion criteria [cross-sectional, case-control, and prospective cohort studies and randomized clinical trials (RCTs) published in English and excluded nonoriginal articles]. Data were pooled by the generic inverse variance method using the random effects model and expressed as standardized mean difference (SMD). Heterogeneity was identified using the Cochran Q test and quantified by the I2 statistic. A total of 8 original cross-sectional studies were included for the quantitative meta-analysis, comprising a total of 13,733 participants from 5 countries. A positive association between adherence to the MedDiet and TL was observed in all meta-analyses, with the exception of those conducted only in men: SMD (95% CI) of 0.130 (0.029; 0.231) for all subjects, 0.078 (0.005; 0.152) for women, and 0.095 (-0.005; 0.195) for men. Only 1 prospective cohort study and 1 RCT were identified, therefore, we could not undertake a meta-analysis for these study designs. The present meta-analysis of cross-sectional studies demonstrates that higher MedDiet adherence is associated with longer TL. At the same time, larger and high-quality prospective studies and clinical trials are warranted to confirm this association.
| S-EPMC7666892 | biostudies-literature
Project description:Background: Over the past two decades, various novel disease-modifying drugs for multiple sclerosis (MS) have been approved. However, there is high variability in the patient response to the available medications, which is hypothesized to be partly attributed to genetics. Objectives: To conduct a systematic review of the current literature on the pharmacogenomics of MS therapy. Methods: A systematic literature search was conducted using PubMed/MEDLINE database searching for articles investigating a role of genetic variation in response to disease-modifying MS treatments, published in the English language up to October 9th, 2018. PRISMA guidelines for systematic reviews were applied. Studies were included if they investigated response or nonresponse to MS treatment defined as relapse rate, by expanded disability status scale score or based on magnetic resonance imaging. The following data were extracted: first author's last name, year of publication, PMID number, sample size, ethnicity of patients, method, genes, and polymorphisms tested, outcome, significant associations with corresponding P-values and confidence intervals, response criteria, and duration of the follow-up period. Results: Overall, 48 articles published up to October 2018, evaluating response to interferon-beta, glatiramer acetate, mitoxantrone, and natalizumab, met our inclusion criteria and were included in this review. Among those, we identified 42 (87.5%) candidate gene studies and 6 (12.5%) genome-wide association studies. Existing pharmacogenomic evidence is mainly based on the results of individual studies, or on results of multiple studies, which often lack consistency. In recent years, hypothesis-free approaches identified novel candidate genes that remain to be validated. Various study designs, including the definition of clinical response, duration of the follow-up period, and methodology as well as moderate sample sizes, likely contributed to discordances between studies. However, some of the significant associations were identified in the same genes, or in the genes involved in the same biological pathways. Conclusions: At the moment, there is no available clinically actionable pharmacogenomic biomarker that would enable more personalized treatment of MS. More large-scale studies with uniform design are needed to identify novel and validate existing pharmacogenomics findings. Furthermore, studies investigating associations between rare variants and treatment response in MS patients, using next-generation sequencing technologies are warranted.
| S-EPMC6399303 | biostudies-literature
Project description:BackgroundNeurofilament proteins have been extensively studied in relapsing-remitting multiple sclerosis, where they are promising biomarkers of disease activity and treatment response. Their role in progressive multiple sclerosis, where there is a particularly urgent need for improved biomarkers, is less clear. The objectives of this systematic review are to summarise the literature on neurofilament light and heavy in progressive multiple sclerosis, addressing key questions.MethodsA systematic search of PubMed, Embase, Web of Science and Scopus identified 355 potential sources. 76 relevant sources were qualitatively reviewed using QUADAS-2 criteria, and 17 were identified as at low risk of bias. We summarise the findings from all relevant sources, and separately from the 17 high-quality studies.ResultsDifferences in neurofilament light between relapsing-remitting and progressive multiple sclerosis appear to be explained by differences in covariates. Neurofilament light is consistently associated with current inflammatory activity and future brain atrophy in progressive multiple sclerosis, and is consistently shown to be a marker of treatment response with immunosuppressive disease-modifying therapies. Associations with current or future disability are inconsistent, and there is no evidence of NFL being a responsive marker of purportedly neuroprotective treatments. Evidence on neurofilament heavy is more limited and inconsistent.ConclusionsNeurofilament light has shown consistent utility as a biomarker of neuroinflammation, future brain atrophy and immunosuppressive treatment response at a group level. Neither neurofilament light or heavy has shown a consistent treatment response to neuroprotective disease-modifying therapies, which will require further data from successful randomised controlled trials.
| S-EPMC8357650 | biostudies-literature
Project description:The aim of this systematic review was to evaluate the existing evidence on the effectiveness and safety of Tai chi, which is critical to provide guidelines for clinicians to improve symptomatic management in patients with multiple sclerosis (MS). After performing electronic and manual searches of many sources, ten relevant peer-reviewed studies that met the inclusion criteria were retrieved. The existing evidence supports the effectiveness of Tai chi on improving quality of life (QOL) and functional balance in MS patients. A small number of these studies also reported the positive effect of Tai chi on flexibility, leg strength, gait, and pain. The effect of Tai chi on fatigue is inconsistent across studies. Although the findings demonstrate beneficial effects on improving outcome measures, especially for functional balance and QOL improvements, a conclusive claim should be made carefully for reasons such as methodological flaws, small sample size, lack of specific-disease instruments, unclear description of Tai chi protocol, unreported safety of Tai chi, and insufficient follow-up as documented by the existing literature. Future research should recruit a larger number of participants and utilize the experimental design with a long-term follow-up to ascertain the benefits of Tai chi for MS patients.
| S-EPMC5300172 | biostudies-literature