Abstract
In multiple sclerosis (MS), there is a possible relationship with viral infection, evidenced by clinical evidence of an implication of infectious events with disease onset and/or relapse. The aim of this research is to study how human herpesvirus (HHVs) infections might dysregulate the innate immune system and impact autoimmune responses in MS. We analyzed 100 MS relapsing remitting patients, in the remission phase, 100 healthy controls and 100 subjects with other inflammatory neurological diseases (OIND) (neuro-lupus) for their immune response to HHV infection. We evaluated NK cell response, levels of HHVs DNA, IgG and pro- and anti-inflammatory cytokines. The results demonstrated that the presence of KIR2DL2 expression on NK cells increased the susceptibility of MS patients to HHV infections. We showed an increased susceptibility mainly to EBV and HHV-6 infections in MS patients carrying the KIR2DL2 receptor and HLA-C1 ligand. The highest HHV-6 viral load was observed in MS patients, with an increased percentage of subjects positive for IgG against HHV-6 in KIR2DL2-positive MS and OIND subjects compared to controls. MS and OIND patients showed the highest levels of IL-8, IL-12p70, IL-10 and TNF-alpha in comparison with control subjects. Interestingly, MS and OIND patients showed similar levels of IL-8, while MS patients presented higher IL-12p70, TNF-alpha and IL-10 levels in comparison with OIND patients. We can hypothesize that HHVs’ reactivation, by inducing immune activation via also molecular mimicry, may have the ability to induce autoimmunity and cause tissue damage and consequent MS lesion development.
Highlights
In multiple sclerosis (MS), there is a possible relationship with viral infection, evidenced by clinical evidence of an implication of infectious events with disease onset and/or relapse
Patients (p = 0.0007; Fisher exact test). These results showed that the expression of the KIR2DL2 receptor seems to correlate with the increased positivity for anti-Epstein–Barr virus (EBV), anti-human herpesvirus (HHVs)-6 and anti-HSV-1 IgG; we assessed the levels of positivity for EBV, human herpesvirus 6 (HHV-6) and HSV-1 IgG in the three populations
MS and other inflammatory neurological diseases (OIND) patients showed the highest levels of IL-8, IL-12p70, IL-10 and TNFalpha in comparison with control subjects (Figure 7; p
Summary
In multiple sclerosis (MS), there is a possible relationship with viral infection, evidenced by clinical evidence of an implication of infectious events with disease onset and/or relapse. The viral infection can directly infect the central nervous system (CNS) and induce an inflammatory response that might result in brain damage. The latent infection typical of herpesviruses might reactivate resulting in disease relapse. The reactivation of viral infection can induce lymphocyte activation and the secretion of pro-inflammatory cytokines that affect cell-specific functions and enhance neurodegeneration [1]. Herpesviridae have shown a possible association with MS, resulting as valuable biomarker candidates of disease progression and therapy outcome. Their preferential tropism for CNS and their latent persisting infections that enable their immune-escape, account for their potential pathogenic role in neuroinflammation, resulting in the persistence of chronic inflammation and the accumulation of neurological deficits. EBV reactivation has been linked to disease activity in early
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