An autoantibody signature predictive for multiple sclerosis, 2024, Colin R. Zamecnik et al

Abstract
Although B cells are implicated in multiple sclerosis (MS) pathophysiology, a predictive or diagnostic autoantibody remains elusive.

In this study, the Department of Defense Serum Repository (DoDSR), a cohort of over 10 million individuals, was used to generate whole-proteome autoantibody profiles of hundreds of patients with MS (PwMS) years before and subsequently after MS onset. This analysis defines a unique cluster in approximately 10% of PwMS who share an autoantibody signature against a common motif that has similarity with many human pathogens. These patients exhibit antibody reactivity years before developing MS symptoms and have higher levels of serum neurofilament light (sNfL) compared to other PwMS.

Furthermore, this profile is preserved over time, providing molecular evidence for an immunologically active preclinical period years before clinical onset. This autoantibody reactivity was validated in samples from a separate incident MS cohort in both cerebrospinal fluid and serum, where it is highly specific for patients eventually diagnosed with MS.

This signature is a starting point for further immunological characterization of this MS patient subset and may be clinically useful as an antigen-specific biomarker for high-risk patients with clinically or radiologically isolated neuroinflammatory syndromes.

https://www.nature.com/articles/s41591-024-02938-3

 

Blood Biomarker Reveals Signs of MS Years Before

LINK

 

I am not sure that the antibody reactivity can really be called an autoantibody. They seem to have identified it using peptides and antibodies to peptides are very hard to interpret in terms of real-life in vivo antibody reactivity. If the peptides also look like lots of micro-organisms maybe they are just peptides you find anywhere.

Nevertheless, it makes sense for pwMS to have a specific antibody profile before onset.
Perhaps what is most interesting that this does not seem to be a reactivity to one specific Brin protein. It has always been puzzle that no clear autoimmune response to brain shows up in MS. But it makes sense if there isn't. To me the disease looks much more like a problem with B cells (of any sort) getting in to brain by mistake, where they can survive because for some reason brain is a place they can exist in (unlike most tissues). That suggests that the antibody specificity may have more to do with getting into brain than actually reacting with brain.

And having antibodies five years before disease goes along with the other autoimmune B cell diseases. By the time I am dead people may have come round to the idea that these are really all B cell diseases!!

 

Always appreciate your insights and knowledge @Jonathan Edwards