Environmental Factors Associated with Disease Progression after the First Demyelinating Event: Results from the Multi-Center SET Study

Abstract

ObjectivesTo investigate the associations of environmental MS risk factors with clinical and MRI measures of progression in high-risk clinically isolated syndromes (CIS) after the first demyelinating event.MethodsWe analyzed 211 CIS patients (age: 28.9±7.8 years) enrolled in the SET study, a multi-center study of high-risk CIS patients. Pre-treatment samples were analyzed for IgG antibodies against cytomegalovirus (anti-CMV), Epstein Barr virus (EBV) early nuclear antigen-1 (EBNA-1), viral capsid antigen (VCA), early antigen-diffuse (EA-D), 25 hydroxy-vitamin D3 and cotinine levels and HLA DRB1*1501 status. The inclusion criteria required evaluation within 4 months of the initial demyelinating event, 2 or more brain MRI lesions and the presence of two or more oligoclonal bands in cerebrospinal fluid. All patients were treated with interferon-beta. Clinical and MRI assessments were obtained at baseline, 6, 12, and 24 months.ResultsThe time to first relapse decreased and the number of relapses increased with anti-CMV IgG positivity. Smoking was associated with increased number and volume of contrast-enhancing lesions (CEL) during the 2-year period. The cumulative number of CEL and T2 lesions during the 2-year period was greater for individuals in the highest quartile of anti-EBV VCA IgG antibodies. The percent loss of brain volume was increased for those in the highest quartile of with anti-EBV VCA IgG antibodies.ConclusionsRelapses in CIS patients were associated with CMV positivity whereas anti-EBV VCA positivity was associated with progression on MRI measures, including accumulation of CEL and T2 lesions and development of brain atrophy.

No association of multiple sclerosis activity and progression with EBV or tobacco use in BENEFIT

“…2-4 Two studies on the effects of smoking and CIS report conflicting results regarding the association between smoking and conversion to clinically definite MS. 2,5 In this study, we examined whether serum levels of anti-EBV IgG antibodies or cotinine, a marker of tobacco use, are associated with early MS disease activity and progression among †Deceased.…”

“…Three prior studies examining EBV and MS activity and/or progression among patients with clinically isolated syndrome (CIS) (first neurologic event suggestive of MS) suggest there is no association with conversion to MS, but have shown mixed results regarding activity and progression. [2][3][4] Two studies on the effects of smoking and CIS report conflicting results regarding the association between smoking and conversion to clinically definite MS. 2,5 In this study, we examined whether serum levels of anti-EBV IgG antibodies or cotinine, a marker of tobacco use, are associated with early MS disease activity and progression among †Deceased. participants in the Betaferon/Betaseron in Newly Emerging Multiple Sclerosis for Initial Treatment (BENEFIT) clinical trial, a cohort of patients who were enrolled and randomized to receive either interferon beta-1b or placebo soon after experiencing a CIS.…”

“…There were 3 outcomes of interest: (1) time to conversion from CIS to MS (either CDMS or MDMS); (2) relapse rates and changes in EDSS score; and (3) changes in number of active lesions, volume of T2 lesions, and brain volume. To minimize reverse causation and changes possibly due to resolution of the CIS, month 6 was considered baseline in analyses of clinical and MRI outcomes, except for change in T2 lesion volume and brain volume in which analyses at month 12 were considered baseline because volume measures in the first year may be affected by the acute inflammation of CIS (e.g., resolution of edema or pseudoatrophy).…”

Serum lipid profile changes predict neurodegeneration in interferon-β1a-treated multiple sclerosis patients

“…The SET study (27) was a prospective longitudinal observational clinical study that involved eight centers in the Czech Republic (clin.gov # NCT01592474). The Ethics Committees of all participating centers approved the study protocol.…”

TLR2 Stimulation Regulates the Balance between Regulatory T Cell and Th17 Function: A Novel Mechanism of Reduced Regulatory T Cell Function in Multiple Sclerosis

“…Thus, TLR2 effects on IL-6 and STAT3 could underpin such effects of infections in vivo. Therefore, acute infections could facilitate disease exacerbations, whereas repeated infections may contribute to the gradual disease progression that is commonly observed in MS patients (67).…”