Multiple Sclerosis and the impact of Epstein-Barr Virus and other Neurotropic Viruses
| Autor: | Nielsen, Anne Julie Heiden |
|---|---|
| Přispěvatelé: | Houen, Gunnar, Troelsen, Jesper |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: | |
| Popis: | Multipel sclerose (MS) er en kronisk inflammatorisk autoimmun sygdom, der forårsager degenerering af myelinskederne i centralnervesystemet. MS ætiologien er stadig ukendt, men en kombination af genetisk prædisposition og miljømæssige faktorer som Epstein-Barr-virus (EBV) er den mest fornuftige teori. EBV er den forårsagende virus til infektiøs mononukleose (IM), og EBV inficerer primært B-celler. Tidligere undersøgelser har afsløret forbindelse mellem humane herpesvirus (HHV), i særdeleshed EBV, og MS. Andre forskningsgrupper har undersøgt indflydelsen af forskellige neurotrope vira som giver mæslinger, fåresyge og rubella (røde hunde). De vigtigste diagnostiske midler til at stille diagnosen MS i dag, er MRI scanninger og undersøgelsen af intratekal produktion af antistoffer ved tilstedeværelsen af oligoklonale bånd (OCB) og et forhøjet IgG-indeks.I dette projekt undersøges immunresponset mod EBV, andre HHV og de neurotrope vira, mæslinger, fåresyge og rubella ved hjælp af ELISA teknik i serum og CSF prøver fra MS patienter, sammenlignet med patienter med synsnervebetændelse (ON) som kan være en form for forstadie til MS, og forskellige kontrolgrupper. Et antigenpanel, der kaldes EZMMR-panelet, bestående af EBV (EBNA-1), VZV, mæslinger, fåresyge og rubella virus antigener blev opfundet, og resultaterne viste et signifikant forhøjet niveau af serum- og CSF IgG antistoffer rettet mod EBNA-1, VZV, mæslinger og fåresyge i patienter med relapsing-remitting MS (RRMS), men ingen forskel i rubella antistoffer. Det specifikke antistof index (AI) var udregnet for at bestemme om de specifikke antistoffer var syntetiseret intratekalt. EZMMR panelets følsomhed vedrørende RRMS patienter var ca. 50%, hvis der kræves tre positive AI og ca. 85%, hvis der kun kræves to positive AI. Sammenlignet med MRZ panelet, hvor kun 50% af RRMS-patienterne havde to positive AI, viste EZMMR-panelet bedre følsomhed. Det var desværre ikke muligt at bestemme specificiteten. Som konklusion, understøtter de opnåede resultater i dette studie teorien om at forskellige vira spiller en stor rolle i MS ætiologien og især EBV. Det er stadig ukendt om vira er den primære årsag til MS, eller den øgede forekomst af antistoffer blot er en konsekvens af sygdommen. Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease causing degeneration of the myelin sheaths of the central nervous system. The etiology of MS is still unknown, but a combination of a genetic predisposition and environmental triggers as Epstein-Barr virus (EBV) is the most reasonable theory. EBV is the causative agent of infectious mononucleosis (IM), and the virus infects primarily B cells. Previous studies have revealed a connection between human herpes viruses (HHVs), especially EBV, and MS, and many research groups have also investigated the impact of different neurotropic viruses like measles, mumps and rubella. The most important tools today in the diagnosis of MS are MRI scans and the investigation of intrathecal production of antibodies, by the presence of oligoclonal bands (OCBs) and an elevated IgG-index.In this project, the immune response towards EBV, other HHVs and the neurotropic viruses measles, mumps and rubella are conducted by ELISA technique in serum and CSF samples from MS patients, compared to patients diagnosed with optic neuritis (ON) which can be a precursor of MS, and various control groups. An antigen panel called the EZMMR panel, consisting of EBV (EBNA-1), VZV, measles, mumps and rubella virus antigens was invented, and the results showed a significant elevated level of serum and CSF IgG antibodies directed against EBNA-1, VZV, measles and mumps in relapsing-remitting MS (RRMS) patients, but no difference regarding rubella antibodies. The specific antibody index (AI) was calculated, to determine if the specific antibodies were intrathecal synthesized. The sensitivity of the EZMMR panel regarding RRMS patients was approximately 50% if three positive AIs were required, and approximately 85% if only two positive AIs were required. Compared with the MRZ panel where only 50% of the RRMS patients had two positive AIs, the EZMMR panel revealed improved sensitivity. Unfortunately, it was not possible to determine the specificity.In conclusion, the results obtained in this study support the theory of the impact of viruses according to MS etiology, and especially EBV. It is still unknown if the viruses are the primary pathogenic agents, and how they are related according to development of MS, or whether the increased prevalence of antibodies just is a consequence of the disease. |
| Databáze: | OpenAIRE |
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