Quintana FJ et al. Epitope spreading as an early pathogenic event in paediatric multiple sclerosis. Neurology December, 2014 vol. 83 2219-2226
Objectives: For most adults with initial clinical presentation of multiple sclerosis (MS), biological disease was likely initiated many years prior. Paediatric-onset MS provides an opportunity to study early disease processes.
Methods: Using antigen microarrays, including CNS-related proteins, lipids, and other autoantigens, we studied early immunologic events involved in clinical onset of paediatric MS. Serum samples were collected at the time of incident acquired CNS demyelinating syndromes (ADS) in children who, in subsequent prospective follow-up, were ascertained to have either pediatric MS (ADS-MS) or a monophasic illness (ADS-mono). Samples were obtained both at the time of ADS presentation and 3 months into follow-up. We used an initial training set of samples to implicate antibody signatures associated with each group, and then a test set. An additional set of follow-up samples (stability set) was used as a form of internal validation.
Results: Children with ADS-MS tended to have distinguishable serum antibody patterns both at the time of ADS presentation and 3 months into follow-up. At the time of ADS, serum samples from patients with ADS-MS or ADS-mono reacted against similar numbers of CNS antigens, although CNS antigens implicated in adult MS were more often targeted in children with ADS-MS. The follow-up ADS-MS samples reacted against a broader panel of CNS antigens, while corresponding ADS-mono samples exhibited a contraction of the initial antibody response.
Conclusions: Our findings in this prospective cohort of paediatric-onset CNS demyelinating diseases point to an active process of epitope spreading during early stages of MS, not seen in monophasic CNS inflammatory conditions.
This is very simple, develop treatments targeted at boosting immunoregulatory mechanisms (targets the entire autoantibody response) or control the effector T cells at an antigen-specific level (e.g. targeting MOG, PLP, MBP, H. pylori, CNPase, ssDNA) using vaccines. And there you have it, the cure for MS – or is it…