Abstract
BackgroundThe 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.ObjectiveTo perform a systematic review and meta-analysis and to assess qualitative and quantitative evidence on the expression of HERV families in MS patients.MethodsMedline, 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.Results43 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.ConclusionsThis systematic review and meta-analysis shows an association between expression of HERVs, and in particular the HERV-W family, and MS.
Highlights
Multiple Sclerosis (MS) is a chronic demyelinating disease of the central nervous system (CNS) and one of the most common causes of neurological disability in young adults, with a higher incidence in women than men [1]
The analysis showed an association between expression of all Human Endogenous Retrovirus (HERVs) families and MS
This systematic review and meta-analysis shows an association between expression of HERVs, and in particular the HERV-W family, and MS
Summary
The online search identified 324 articles (Fig 2). After removing the duplicates, 244 articles were retained. In 15 studies MSRV/HERV-Wenv [10, 14,15,16,17,18,19] or MSRV/HERV-Wpol [5, 8, 17, 20,21,22,23,24,25] RNA or protein were found to be increased in serum/plasma or PBMC of MS patients compared to control groups (HC or OND) by different techniques [RT-PCR, Flow cytometry (FC) and ELISA]. By contrast, using the same techniques, a Canadian group found an increased expression of HERVWE1env RNA (syncytin-1) but not MSRV/ HERV-Wenv, in the brains of MS patients compared to OND [7, 28, 33, 34]. For our meta-analysis of the association of MSRV/HERV-W with MS, 12 articles were suitable for inclusion according to the criteria described in the Methods Together, these studies included 478 MS patients, 330 HC and 145 OND.
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