, according to a new study.
Investigators screened blood samples from 250 individuals with MS drawn 5 years before and 1 year after symptom onset, profiled MS-related autoantibodies, and compared the sample with 250 matched controls.
A unique cluster of autoantibodies was found in 10% of people with MS, appearing up to 5 years before the onset of clinical symptoms and remaining higher 1 year after diagnosis.
“Our work demonstrates that a subset of MS patients has antibodies that react to a common protein motif, both before, during, and after diagnosis and symptom onset,” said lead investigator Colin R. Zamecnik, PhD, a postdoctoral researcher at UCSF School of Medicine, University of California, San Francisco.
Such a discovery could aid in early diagnosis, Dr. Zamecnik added. MS treatments “have gotten much better in the last 15-20 years and evidence shows early treatment can improve outcomes,” he said.
The study was published online in Nature Medicine.
Seeking Earlier Diagnosis
Previous research shows that nonspecific neurologic episodes occur more frequently in people who received an MS diagnosis later in life, pointing to the possibility of an MS prodrome, the authors noted.
These neurologic episodes may be indicative of ongoing neuroinflammatory processes in the preclinical period, they added. Studies in several other autoimmune diseases show that diagnostic autoantibodies can appear years before symptom onset. However, no such antibodies have previously been identified in MS patients.
To investigate, the researchers turned to data from a large, prospective incident MS cohort assembled during the Gulf War era in more than 10 million US military veterans.
Records of those with the earliest diagnosis (an average of 5 years before symptom onset) and 1 year after the first attack were analyzed, and matched controls were selected.
Investigators used a technique called phage display immunoprecipitation sequencing to screen human blood for antibodies. They conducted a whole-proteome autoantibody screen and serum neurofilament light (sNfL) measurements on these samples in both case patients and controls at the same time points.
Early Signs of Injury
In the preclinical serum samples, sNfL levels were higher nearer the date of diagnosis and significantly higher in post- versus pre-onset samples in people with MS. “Together, these data provide evidence that at least some people with MS exhibit early signs of neuroaxonal injury long before onset of symptoms,” the authors noted.
Analysis of the collection of peptides, described by the investigators as an “autoantibody signature,” was consistent over time and was present regardless of diagnosis.
Further analysis of the autoantibodies revealed a characteristic protein motif found in common viruses, including Epstein-Barr virus (EBV) and hepatitis C virus, among others.
The motif “shares remarkable similarity to those found on many pathogens that infect humans, including EBV, which is known to be a risk factor for development of MS,” Dr. Zamecnik said.
The researchers validated these findings by analyzing serum and cerebrospinal fluid samples from participants in ORIGINS, an MS cohort at the University of California, San Francisco, that enrolled patients at clinical onset. As with the other cohort, 10% of patients had the autoantibody signature.
The investigators added that the findings detail some of the first autoantigen-specific biomarkers found in preclinical MS.
“Taken together, our future work will focus on profiling these patients more closely over time to see how they differ from their counterparts and gives further evidence of viral-host crosstalk as a hallmark of this disease,” Dr. Zamecnik said.