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ACTRIMS 2026 | Multiplex proteomics reveals a distinct inflammatory signature in RIS

Raphael Schneider, MD, PhD, FRCPC, CIP
, St. Michael’s Hospital, Toronto, Canada, discusses a cohort study of radiologically isolated syndrome (RIS), in which individuals with MRI findings suggestive of multiple sclerosis (MS), but no clinical symptoms, are closely monitored. Dr Schneider highlights the use of multiplex proteomic analysis to measure nearly 100 proteins simultaneously. This approach identified a distinct inflammatory signature that precedes radiological disease activity and the onset of clinical symptoms. This interview is part of our coverage of the 11th Annual Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum, held in San Diego, CA.

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Transcript

So we’re looking into a very specific cohort of people with radiologically isolated syndrome here at the BARLO MS Center in Toronto. And this is a group of patients who come to medical attention because of an MRI scan that looks like that of a person with MS without ever having experienced any typical symptoms. And what we then do is we ask them to participate in our cohort study. And then if they agree, they come once a year, they get neurological examinations done, cognitive testing done, repeat MRIs done...

So we’re looking into a very specific cohort of people with radiologically isolated syndrome here at the BARLO MS Center in Toronto. And this is a group of patients who come to medical attention because of an MRI scan that looks like that of a person with MS without ever having experienced any typical symptoms. And what we then do is we ask them to participate in our cohort study. And then if they agree, they come once a year, they get neurological examinations done, cognitive testing done, repeat MRIs done. And we also take blood for biomarker studies. And recently at the ACTRIMS Forum, I’ve shared our data on the protein biomarkers. We’ve oftentimes done studies where we’ve only looked at one or maybe two of these protein biomarkers, and we found a few interesting things when it comes to a protein called neurofilament light protein, or more recently, glial fibrillary acidic protein, and also chitinase 3-like-1. So these were interesting, smaller cohort studies that, again, looked into single markers. And we thought, well, if we’re always going in with a hypothesis that one protein is going to be telling us a lot about these people’s future, well, maybe we’re missing somewhat the bigger picture. And this is where we ended up saying, well, we would need to move forward and do something that’s called multiplexing, basically measuring almost 100 proteins at the same time. And including data from previous studies where we had imaging and also the single biomarkers, we then created a more complete kind of setup where we were looking into these multiplex biomarkers using a platform that’s called Olink. And what we found there was an interesting signature where we saw that when individuals were developing more MRI lesions over time, and also those who developed symptoms over time, well, in that group, we saw an increase of certain inflammatory proteins already at the baseline visit, meaning that proteins such as IL-17 were increased and IL-10 decreased a year before we saw this radiological activity. So that really means for us that we probably should be looking into immune biology markers in addition to the neurobiology markers that we’ve studied before. And we’re now looking into validating these results in larger cohorts.

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Disclosures

Dr Raphael Schneider has received consulting fees from Novartis and EMD Serono and payments or honoraria for lectures, presentations, and educational events from Biogen-Idec, Sanofi-Genzyme, EMD Serono, and Roche. Dr Schneider has participated on advisory boards for Novartis and EMD Serono. He has also received support for attending scientific meetings from EMD Serono.