Abstract
ObjectiveTo analyze the titers of the IgG and IgM antibodies against human herpesvirus 6A/B (HHV-6A/B) in multiple sclerosis (MS) patients treated with different disease modified therapies (DMTs) along two-years of follow-up.MethodsWe collected 2163 serum samples from 596 MS; for 301 MS patients a 2-years follow-up was performed. Serum samples of 337 healthy controls were also analyzed. Anti-HHV-6A/B IgG and IgM were analyzed by ELISA (Panbio).ResultsWe found that 129/187 (69.0%) MS patients with a decrease of the anti-HHV-6A/B IgG titers after 2-years with DMTs were free of relapses and progression vs. 46/113 (40.7%) of MS patients with an increase of the anti-HHV-6A/B IgG titers (p = 0.0000015); the higher significance was found for natalizumab. Furthermore, we found that anti-HHV-6A/B IgG titers reached their highest value two weeks before the relapse (p = 0.0142), while the anti-HHV-6A/B IgM titers reached their highest value one month before the relapse (p = 0.0344).ConclusionThe measurement of the anti-HHV-6A/B IgG titers could be a good biomarker of clinical response to the different DMTs. The increase of the anti-HHV-6A/B IgG and IgM titers predicts the upcoming clinical relapses. However, further longitudinal studies are needed to validate these results.
Highlights
Multiple sclerosis (MS) is an inflammatory and degenerative neurological disease in which damage to the central nervous system causes widespread dysfunction [1]
No virus or other environmental agents have been definitively implicated as a causative factor of MS, certain human herpesviruses (HHVs) have been linked with the development of MS [5], especially the Epstein-Barr virus (EBV) [6,7,8], and the formerly known as HHV-6 [9,10,11]; some authors have described a possible relation between HHV-6B and MS [12], it appears that HHV-6A could be mainly associated with MS [13,14,15]
When we analyzed only those serum samples collected when MS patients were untreated (Table 2), we found that the antiHHV-6A/B IgG prevalence was 98.0% (295/301) vs. 93.4% (315/337) in healthy controls (p = 0.005), and the mean titer was 26.8 Panbio units (PU) vs. 23.1 PU in healthy controls (p = 0.00002)
Summary
Multiple sclerosis (MS) is an inflammatory and degenerative neurological disease in which damage to the central nervous system causes widespread dysfunction [1]. There are increasing evidences that a number of environmental factors are important in the development and course of MS. No virus or other environmental agents have been definitively implicated as a causative factor of MS, certain human herpesviruses (HHVs) have been linked with the development of MS [5], especially the Epstein-Barr virus (EBV) [6,7,8], and the formerly known as HHV-6 [9,10,11]; some authors have described a possible relation between HHV-6B and MS [12], it appears that HHV-6A could be mainly associated with MS [13,14,15]. The aim of this study was to analyze the titers of the IgG and IgM antibodies against HHV-6A/B in MS patients treated with different DMTs along two-years of follow-up
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