Prevalence of human herpesvirus U94/REP antibodies and DNA in Tunisian multiple sclerosis patients

Abstract

Human herpesvirus 6 (HHV-6) has been linked to the pathogenesis of multiple sclerosis (MS). Based on antibody detection and quantitative HHV-6 polymerase chain reaction assay, this study aimed to analyze the possible association between infection with HHV-6 and MS. A total of 131 serum samples were analyzed by ELISA for the presence of specific antibodies to HHV-6 latency-associated U94/REP protein: 68 serum samples from 60 MS patients (20 in relapse and 48 in remission phase) and 63 serum samples from 63 healthy controls. Real-time quantitative PCR for HHV-6 U94/rep DNA was also performed in total blood of MS patients and healthy controls. The serological analysis by ELISA showed that MS patients had increased prevalence and titers of anti-U94/REP immunoglobulins in comparison with control group (seroprevalence 51.47 % versus 28.57 % and mean titer of positive samples 1:248 versus 1:110; p=0.0005), with significant difference between relapse and remission phases. HHV-6 DNA was detected in 4 of 60 MS patients (6.66 %) and in 2 of 63 healthy controls (3.17 %), confirming previous data of prevalence obtained by qualitative nested PCR. However, viral load was higher in MS patients compared to controls, and differences were statistically significant (p=0.02). The results show that, in spite of the low presence of HHV-6 DNA in peripheral blood, MS patients have increased prevalence and titer of IgGs reacting with HHV-6 latency-associated U94/REP protein.

Evidence linking HHV-6 with multiple sclerosis: an update

“…A 2013 study examined antibodies to a latency-promoting protein, U94/REP, and found elevated IgG levels in Tunisian MS patients compared to controls; for eight patients with samples collected during relapsing and remitting phases, significantly higher titers were detected during the relapsing phases [31]. The finding of an elevated U94 IgG response in MS patients versus controls agrees with previous findings in an Italian cohort [32], and adds the observation of higher titers during relapse versus remission.…”

Transcriptome sequencing of neurologic diseases associated genes in HHV-6A infected human astrocyte

“…YKL-40 has been proposed as a biomarker of multiple sclerosis [90]. CSF level of YKL-40 is increased in MS [91] and is a prognostic marker in MS [92]. Enhanced skin expression of IFIH1 (MDA5) in dermatomyositis and related autoimmune diseases [93].…”

Mini review article. Human herpesvirus-6 and the etiology of multiple sclerosis: a literature review

“…Fredj et al [38] reported HHV-6 DNA in peripheral blood samples from 6.1% of patients with RRMS in remission and in 2.0% of healthy controls and Sotelo et al [36] in PBMCs from 2% of patients with RRMS in remission and in none of the healthy controls. Ben-Fredj et al [42] reported HHV-6 DNA in whole blood from 6.7% of patients with MS from Tunisia and in 3.2% of healthy controls and Hon et al [37] in 3.2% of patients with MS from South Africa and absent in healthy controls. Ablashi et al [41] reported higher prevalence rates; the authors reported viral DNA in PBMCs from 66.7% of patients with MS in remission, but also in 60.0% of healthy controls, and therefore equally higher for both patients and controls.…”