Blood samples have emerged as a potential treasure trove of insights into the early stages of multiple sclerosis (MS), offering the possibility of identifying individuals at high risk long before clinical symptoms appear.
Blood samples revealed a distinct autoantibody signature in a subgroup of individuals with MS well before the onset of clinical symptoms, according to findings reported by Dr Michael Wilson and colleagues from the University of California San Francisco (UCSF).
This specific set of autoantibodies emerged in approximately 10% of MS patients up to five years before the appearance of symptoms. These autoantibodies showed affinity towards both human cells and common pathogens and were associated with elevated levels of serum neurofilament light (NfL).
The persistence of this autoantibody profile over time indicates an immunologically active preclinical phase occurring years before the onset of clinical symptoms, as detailed by Wilson and the research team in Nature Medicine.
This autoantibody signature could serve as a valuable starting point for further characterisation of this patient subset and may hold clinical utility as an antigen-specific biomarker for identifying high-risk individuals with clinically isolated or radiologically isolated syndromes, the authors stated.
Dr Colin Zamecnik, co-author from UCSF, emphasised the importance of B cells, which produce antibodies, in MS disease progression. He explained that profiling antibodies in individuals with or at risk of developing MS offers valuable insights into the disease and could potentially unveil a biomarker.
The study suggests that a subset of individuals prone to developing MS may possess antibodies targeting a common protein domain found in humans and viruses. Dr Zamecnik noted that these patients exhibit these antibodies many years before symptom onset and continue to have them in both blood and cerebrospinal fluid at the time of their first disease flare.
The research, using data from the Department of Defence Serum Repository, employed phage display immunoprecipitation sequencing (PhIP-Seq) to screen blood samples for autoantibodies. This repository, known for its previous contribution to establishing a link between Epstein-Barr virus and MS, provided samples from over 10 million US armed service members.
In both the Department of Defence and UCSF ORIGINS cohorts, individuals diagnosed with MS exhibited higher serum NfL levels years before their first clinical flare compared to matched controls. Furthermore, approximately 10% of MS patients in both cohorts displayed a distinctive autoantibody pattern predictive of an MS diagnosis.
Although the role of autoantibodies in MS could lead to earlier diagnosis and treatment, potentially moving towards a cure for some MS patients.
Source: Zamecnik, C.R., Sowa, G.M., Abdelhak, A. et al. An autoantibody signature predictive for multiple sclerosis. Nat Med (2024). https://doi.org/10.1038/s41591-024-02938-3.
