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The association between human endogenous retroviruses and multiple sclerosis: A systematic review and meta-analysis.

ABSTRACT: BACKGROUND:The interaction between genetic and environmental factors is crucial to multiple sclerosis (MS) pathogenesis. Human Endogenous Retroviruses (HERVs) are endogenous viral elements of the human genome whose expression is associated with MS. OBJECTIVE:To perform a systematic review and meta-analysis and to assess qualitative and quantitative evidence on the expression of HERV families in MS patients. METHODS:Medline, Embase and the Cochrane Library were searched for published studies on the association of HERVs and MS. Meta-analysis was performed on the HERV-W family. Odds Ratio (OR) and 95% confidence interval (CI) were calculated for association. RESULTS:43 reports were extracted (25 related to HERV-W, 13 to HERV-H, 9 to HERV-K, 5 to HRES-1 and 1 to HER-15 family). The analysis showed an association between expression of all HERV families and MS. For HERV-W, adequate data was available for meta-analysis. Results from meta-analyses of HERV-W were OR = 22.66 (95%CI 6.32 to 81.20) from 4 studies investigating MSRV/HERV-W (MS-associated retrovirus) envelope mRNA in peripheral blood mononuclear cells, OR = 44.11 (95%CI 12.95 to 150.30) from 6 studies of MSRV/HERV-W polymerase mRNA in serum/plasma and OR = 6.00 (95%CI 3.35 to 10.74) from 4 studies of MSRV/HERV-W polymerase mRNA in CSF. CONCLUSIONS:This systematic review and meta-analysis shows an association between expression of HERVs, and in particular the HERV-W family, and MS.

SUBMITTER: Morandi E

PROVIDER: S-EPMC5313176 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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The association between human endogenous retroviruses and multiple sclerosis: A systematic review and meta-analysis.

Morandi Elena E Tanasescu Radu R Tarlinton Rachael E RE Constantinescu Cris S CS Zhang Weiya W Tench Christopher C Gran Bruno B

PloS one 20170216 2

<h4>Background</h4>The interaction between genetic and environmental factors is crucial to multiple sclerosis (MS) pathogenesis. Human Endogenous Retroviruses (HERVs) are endogenous viral elements of the human genome whose expression is associated with MS.<h4>Objective</h4>To perform a systematic review and meta-analysis and to assess qualitative and quantitative evidence on the expression of HERV families in MS patients.<h4>Methods</h4>Medline, Embase and the Cochrane Library were searched for ...[more]

PMID: 28207850

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Project description:Importance:Multiple sclerosis (MS) relapses may be increased in the postpartum period, and whether breastfeeding is associated with reduction in the risk of postpartum relapses remains controversial. Objective:To perform a systematic review and meta-analysis to evaluate whether breastfeeding is associated with reduction in postpartum MS relapses compared with not breastfeeding. Data Sources:PubMed and Embase were searched for studies assessing the association between breastfeeding and MS disease activity published between January 1, 1980, and July 11, 2018, as well as reference lists of selected articles. Study Selection:All study designs assessing the association between breastfeeding and postpartum relapses in MS relative to a comparator group were included. Data Extraction and Synthesis:Study eligibility assessment and extraction of study characteristics, methods, and outcomes, were performed independently by 2 reviewers following PRISMA guidelines. Risk of bias was evaluated by 2 independent reviewers with the ROBINS-I tool for nonrandomized, interventional studies. Findings from studies with data available for the number of women with postpartum relapses in the breastfeeding and nonbreastfeeding groups were combined with a random-effects model. Main Outcomes and Measures:Postpartum MS relapse. Results:The search identified 462 unique citations, and 24 (2974 women) satisfied eligibility criteria and were included, of which 16 were included in the quantitative meta-analysis. The pooled summary odds ratio for the association of breastfeeding with postpartum relapses was 0.63 (95% CI, 0.45-0.88; P?=?.006) compared with a reference of nonbreastfeeding. Pooled adjusted hazard ratio across 4 studies that reported this finding was 0.57 (95% CI, 0.38-0.85; P?=?.006). There was moderate heterogeneity (I2?=?48%), which was explained by variable prepregnancy relapse rate, postpartum follow-up duration, and the publication year. A stronger association was seen in studies of exclusive rather than nonexclusive breastfeeding, although both demonstrated an association. Studies were rated at moderate and serious risk of bias, with concern for residual confounding, although sensitivity analysis including only moderate quality studies was consistent with a protective outcome of breastfeeding. Conclusions and Relevance:These findings suggest that breastfeeding is protective against postpartum relapses in MS, although high-quality prospective studies to date are limited and well-designed observational studies that aim to emulate a randomized trial would be of benefit.

Project description:BackgroundA role for Epstein Barr virus (EBV) in multiple sclerosis (MS) has been postulated. Previous systematic reviews found higher prevalences of anti-EBV antibodies in MS patients compared to controls, but many studies have since been published, and there is a need to apply more rigorous systematic review methods.Methodology/principal findingsWe examined the link between EBV and MS by conducting a systematic review and meta-analysis of case-control and cohort studies that examined the prevalence of anti-EBV antibodies in the serum of cases and controls. We searched Medline and Embase databases from 1960 to 2012, with no language restriction. The Mantel-Haenszel odds ratios (OR) for anti-EBV antibodies sero-positivity were calculated, and meta-analysis conducted. Quality assessment was performed using a modified version of the Newcastle Ottawa scale. Thirty-nine studies were included. Quality assessment found most studies reported acceptable selection and comparability of cases and controls. However the majority had poor reporting of ascertainment of exposure. Most studies found a higher sero-prevalence of anti-EBNA IgG and anti-VCA IgG in cases compared to controls. The results for anti-EA IgG were mixed with only half the studies finding a higher sero-prevalence in cases. The meta-analysis showed a significant OR for sero-positivity to anti-EBNA IgG and anti-VCA IgG in MS cases (4.5 [95% confidence interval (CI) 3.3 to 6.6, p<0.00001] and 4.5 [95% CI 2.8 to 7.2, p<0.00001] respectively). However, funnel plot examination suggested publication bias for the reporting of the anti-EBNA IgG. No significant difference in the OR for sero-positivity to anti-EA IgG was found (1.4 [95% CI 0.9 to 2.1, p?=?0.09]).Conclusion/significanceThese findings support previous systematic reviews, however publication bias cannot be excluded. The methodological conduct of studies could be improved, particularly with regard to reporting and conduct of laboratory analyses.

Dataset Information

The association between human endogenous retroviruses and multiple sclerosis: A systematic review and meta-analysis.

Publications

The association between human endogenous retroviruses and multiple sclerosis: A systematic review and meta-analysis.

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