Human herpesvirus 6, Varicella-Zoster virus and oligoclonal bands in demyelinating diseases of the central nervous system
Year: 2016
Type: dissertation
Study design: Observational Study
Abstract: Background: Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) whereby the host immune system attacks against the myelin. MS affects predominantly young adults and leads to neurological disability. Although it has worldwide penetrance, MS has different incidence rates in different parts of the world. The incidence may also vary among different parts of the country, as seen in Finland. The final diagnosis of MS may often be delayed due to the heterogeneity and relapsing nature of the disease. Occurring symptoms depend on the location of the inflammation in the central nervous system. The most common form of the disease is relapsing-remitting multiple sclerosis (RRMS), in which patients typically recover from all of their symptoms. Infections are often seen before the disease progresses or relapses. Therefore, infectious agents, especially viruses, have been under suspicion for triggering an autoimmune reaction that leads to demyelination. Human herpesviruses are considered to be possible triggers for MS pathogenesis. Objective: Most patients who have been diagnosed with MS have oligoclonal bands (OCBs) of immunoglobulins in their cerebrospinal fluid (CSF). The OCBs are intrathecally produced antibodies mainly consisting of IgG, IgA, and IgM class antibodies. Clinically, the most important antibody group in OCB analysis is the IgG class, which was the main focus in this study. The objective was to study if the OCBs of patients contain antibodies against highly neurotropic and common childhood viruses: human herpesvirus-6 (HHV-6) and varicella-zoster virus (VZV). Another objective was to study if the patients, who have virus-reactive OCBs in their CSF, have some distinguishable features. The main aim was to study the possible role of these viruses in the pathogenesis of MS, focusing on the presence of antibodies during the early stages of the disease. Methods: OCB-positive CSF-serum sample pairs were systematically collected over the course of one year. A retrospective re-detection of OCBs by isoelectric focusing (IEF) was made, and HHV-6A, HHV-6B and VZV-reactive OCBs were localized with affinity driven immunoblotting. HHV-6 IgG antibodies were analyzed from the serum with immunofluorescence assay (IFA). The binding capacity of the IgG antibodies was analyzed and the infections (primary vs. past infection) were classified with avidity testing. During the clinical evaluation, the medical records of the patients were analyzed without knowing the results of the IFA or virus-reactive OCBs. This study has been ethically approved. Results: We had 18 immunocompetent adult patients with serologically primary HHV-6A or HHV-6B infections. None of them had any typical signs of a virus infection (e.g. fever or rash). Of those 18 patients 11 were diagnosed with MS with a primary infection during the early stage of the disease. Of 79 patients, 26 had HHV-6A-, HHV-6B-, or VZV reactive OCBs in their CSF. Of those 26 patients 62% were diagnosed with MS and had these virus-reactive OCBs during the early stage of MS. Patients who had any studied virus-reactive OCBs in their CSF seemed to differ from those without, including: more OCBs (p=0.001-0.003), lower protein concentration (p=0.012), and higher IgG index (p=0.007-0.014) in the CSF. They were also younger (p=0.047). Conclusion:Virus-reactive OCBs are possibly associated with MS disease pathogenesis. HHV-6 and VZV may have some association with MS disease. The pathogenesis of multiple sclerosis may have distinguishable subgroups, including pathogenesis triggered by infections with different viruses.
Source: Työväentutkimus Vuosikirja
Author: Jenna Nicklen
Language: English
Subfield: Clinical Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2289297374