Contributions
Abstract: P356
Type: Poster Sessions
Abstract Category: Clinical aspects of MS - Epidemiology
Introduction: The risk of MS subsequent to acute Epstein-Barr virus (EBV) infection manifested as serologically defined infectious mononucleosis (IM) is 2.5 - 3 times higher than expected from population data. While association between EBV and MS was amply confirmed, the reason for the post-IM surplus risk is unknown. Both direct causality from persistent reactivity after IM, and reverse causality due to EBV specific immunodeficiency were proposed, but no hard evidence has been produced in support of any of these hypotheses. The immunological condition of persons who previously experienced acute IM has not been investigated.
Objectives: To reveal persistent inflammatory activity or neurodegeneration several years after IM. Markers which recently showed increased values in MS were selected.
Aims: To examine a direct rather than reverse causality between EBV and MS.
Methods: We examined healthy individuals who had serologically determined IM between 2003 and 2007. Follow-up including a questionnaire, a neurological evaluation and a CSF analysis was performed. The levels of NFl, CXCL13 and YKL-40 were determined with immunochemical methods in the post-IM group (n=22), and in MS control (n=23) and healthy control groups (n=19) with mean age 30, 36 and 26 years.
Results: The CSF level of YKL-40 was increased in the healthy post IM Group, 76.5 (SE 6.21), compared to healthy individuals not reporting previous IM experience, 57.7 (SE 6.88) (p t-test = 0.049, Kruskal-Wallis 0.084). The levels of NFL in the post IM group, 283.8 (SE 20.5) did not deviate from those of the healthy controls, and CXCL13 was below the detection level in most individuals. The NFL, CXCL13 and YKL-40 levels were markedly increased in the MS patients (p < 0.001), practically acting as positive controls.
Discussion: The higher levels of YKL-40 a decade after acute IM was suggestive of a direct rather than inverse link between EBV infection and subsequent inflammatory state, which may be comparable to inflammatory preclinical stages known from MS and other autoimmune diseases. YKL-40, which plays a role in inflammation, proliferation, and angiogenesis, has been evaluated in many inflammatory diseases and is a potential marker for a post IM stage, as IM is known to be a risk factor for several mainly inflammatory conditions including MS. Thus, further studies on the post IM state are warranted.
Disclosure: Daniel Jons: Nothing to disclose. Henrik Zetterberg: Has served at advisory boards for Eli Lilly, Roche Diagnostics and Wave, has received travel support from Teva and is a co-founder of Brain Biomarker Solutions in Gothenburg AB, a GU Ventures-based platform company at the University of Gothenburg. Kai Blennow: Has served at advisory boards for Eli Lilly, Roche Diagnostics and Fujirebio and is a co-founder of Brain Biomarker Solutions in Gothenburg AB, a GU Ventures-based platform company at the University of Gothenburg. Tomas Bergström: Nothing to disclose. Oluf Andersen: Nothing to disclose. Main funding: Swedish ALF grants for university hospitals.
Abstract: P356
Type: Poster Sessions
Abstract Category: Clinical aspects of MS - Epidemiology
Introduction: The risk of MS subsequent to acute Epstein-Barr virus (EBV) infection manifested as serologically defined infectious mononucleosis (IM) is 2.5 - 3 times higher than expected from population data. While association between EBV and MS was amply confirmed, the reason for the post-IM surplus risk is unknown. Both direct causality from persistent reactivity after IM, and reverse causality due to EBV specific immunodeficiency were proposed, but no hard evidence has been produced in support of any of these hypotheses. The immunological condition of persons who previously experienced acute IM has not been investigated.
Objectives: To reveal persistent inflammatory activity or neurodegeneration several years after IM. Markers which recently showed increased values in MS were selected.
Aims: To examine a direct rather than reverse causality between EBV and MS.
Methods: We examined healthy individuals who had serologically determined IM between 2003 and 2007. Follow-up including a questionnaire, a neurological evaluation and a CSF analysis was performed. The levels of NFl, CXCL13 and YKL-40 were determined with immunochemical methods in the post-IM group (n=22), and in MS control (n=23) and healthy control groups (n=19) with mean age 30, 36 and 26 years.
Results: The CSF level of YKL-40 was increased in the healthy post IM Group, 76.5 (SE 6.21), compared to healthy individuals not reporting previous IM experience, 57.7 (SE 6.88) (p t-test = 0.049, Kruskal-Wallis 0.084). The levels of NFL in the post IM group, 283.8 (SE 20.5) did not deviate from those of the healthy controls, and CXCL13 was below the detection level in most individuals. The NFL, CXCL13 and YKL-40 levels were markedly increased in the MS patients (p < 0.001), practically acting as positive controls.
Discussion: The higher levels of YKL-40 a decade after acute IM was suggestive of a direct rather than inverse link between EBV infection and subsequent inflammatory state, which may be comparable to inflammatory preclinical stages known from MS and other autoimmune diseases. YKL-40, which plays a role in inflammation, proliferation, and angiogenesis, has been evaluated in many inflammatory diseases and is a potential marker for a post IM stage, as IM is known to be a risk factor for several mainly inflammatory conditions including MS. Thus, further studies on the post IM state are warranted.
Disclosure: Daniel Jons: Nothing to disclose. Henrik Zetterberg: Has served at advisory boards for Eli Lilly, Roche Diagnostics and Wave, has received travel support from Teva and is a co-founder of Brain Biomarker Solutions in Gothenburg AB, a GU Ventures-based platform company at the University of Gothenburg. Kai Blennow: Has served at advisory boards for Eli Lilly, Roche Diagnostics and Fujirebio and is a co-founder of Brain Biomarker Solutions in Gothenburg AB, a GU Ventures-based platform company at the University of Gothenburg. Tomas Bergström: Nothing to disclose. Oluf Andersen: Nothing to disclose. Main funding: Swedish ALF grants for university hospitals.