Summary: Researchers identified a specific pattern of autoantibodies in the blood that precedes the clinical onset of multiple sclerosis (MS), potentially paving the way for early diagnosis and treatment.
Their study found that 10% of MS patients displayed a unique set of autoantibodies against both human proteins and common pathogens like the Epstein-Barr Virus years before showing symptoms.
These findings could lead to a simple blood test for early detection of MS, allowing for timely intervention with more effective therapies.
The study used blood samples from the U.S. Department of Defense Serum Repository, analyzing samples from before and after the diagnosis of 250 MS patients.
The group analyzed blood from 250 MS patients collected after their diagnosis, plus samples taken five or more years earlier when they joined the military.
The researchers also looked at comparable blood samples from 250 healthy veterans.
Instead, they found that 10% of the MS patients had a striking abundance of autoantibodies years before their diagnosis.
Nature Medicine Abstract An autoantibody signature predictive for multiple sclerosis Although B cells are implicated in multiple sclerosis (MS) pathophysiology, a predictive or diagnostic autoantibody remains elusive.
In summary, prior to the clinical manifestation of multiple sclerosis (MS), a particular pattern of blood autoantibodies has been found by researchers, which may facilitate an early diagnosis and course of treatment. Ten percent of MS patients, according to their research, had a distinct set of autoantibodies against human proteins as well as common pathogens like the Epstein-Barr virus years before they manifested symptoms.
These results may lead to the development of a straightforward blood test for the early diagnosis of multiple sclerosis, facilitating prompt intervention with more potent treatments. With earlier and more targeted treatments on the horizon, this discovery has the potential to revolutionize MS care.
Important Information:.
In 10% of MS patients, autoantibodies that bind to a common viral chemical pattern were discovered by researchers. This suggests that an immune response occurred years before any clinical symptoms appeared.
U.S. blood samples were used in the study. s. Department of Defense Serum Repository, examining samples from 250 MS patients both before and after their diagnosis.
The autoantibody pattern demonstrated remarkable potential as a biomarker, as it was found to be 100% predictive of an MS diagnosis and consistent across different cohorts.
UCSF is the source.
Researchers at UC San Francisco have found a harbinger in the blood of some individuals who went on to develop multiple sclerosis (MS), which could speed up treatment for patients with the disease.
A characteristic set of antibodies against the body’s own proteins is produced by the body in about 1 in 10 MS cases, years before symptoms appear.
The immune attacks on the brain and spinal cord that are characteristic of multiple sclerosis (MS) may be explained by the fact that these autoantibodies appear to bind to both human cells and common pathogens.
The results were April 19 published in Nature Medicine.
Devastating loss of motor control can result from multiple sclerosis (MS), but new treatments can slow the disease’s progression and, for example, keep a patient’s ability to walk.
In the future, the researchers hope that a straightforward blood test will be able to identify the autoantibodies they have identified, providing patients with early access to treatment.
According to UCSF neurologist Michael Wilson, MD, a senior author of the paper, “there’s been a move in the field over the last few decades to treat MS earlier and more aggressively with newer, more potent therapies.”.
When a diagnosis like this is made, patients have hope for a better life and such early intervention becomes more likely. “.
autoimmune diseases and infections being related.
A portion of rare immune responses to common infections are thought to be the cause of autoimmune diseases like multiple sclerosis (MS).
In order to create more effective instruments for identifying the causes of autoimmune diseases, Wilson teamed up with Joe DeRisi, PhD, president of the Chan Zuckerberg Biohub SF and a senior author of the study, in 2014.
They took a method known as phage display immunoprecipitation sequencing (PhIP-Seq), which involves engineering viruses to display flag-like portions of proteins on their surface, and further refined it to screen human blood for autoantibodies.
Autoantibodies against over 10,000 human proteins can be found using PhIP-Seq, which is sufficient to look into almost any autoimmune condition. Utilizing it effectively, they were able to identify a rare autoimmune illness that appeared to be related to testicular cancer in 2019.
Over 900,000 individuals in the US suffer from MS. Diagnoses involving brain MRI scans must be made carefully because the initial symptoms, such as fatigue, dizziness, and spasms, can mimic those of other illnesses.
The scientists reasoned that by revealing the autoantibodies causing the immune attacks associated with multiple sclerosis, the phage display system could open up new avenues for understanding and treating the disease.
First co-author Gavin Sowa, MD, MS, a former UCSF medical student and current internal medicine resident at Northwestern University, and Colin Zamecnik, PhD, a postdoctoral researcher in DeRisi and Wilson’s labs, led the project.
They collaborated with senior author of the paper Mitch Wallin, MD, MPH, of the University of Maryland to look for autoantibodies in the blood of MS patients. These samples came from the U.S. s. Blood samples from armed service members who wish to enlist are kept in the Department of Defense Serum Repository.
The group examined samples taken five years or more prior to their military enlistment, as well as blood from 250 MS patients that had been collected following their diagnosis. Additionally, 250 healthy veterans’ blood samples were examined by the researchers.
With so many participants and samples taken before and after the disease’s clinical onset, Zamecnik called it “a phenomenal cohort of individuals to look at to see how this kind of autoimmunity develops over the course of clinical onset of this disease.”.
A signature that is consistent with MS.
The scientists hypothesized that they would detect an increase in autoantibodies as soon as the initial symptoms of multiple sclerosis (MS) manifested, based on a scant thousandth of a milliliter of blood from each time point.
Rather, they discovered that years prior to their MS diagnosis, 10% of the patients exhibited an incredibly high level of autoantibodies.
The approximately twelve autoantibodies adhered to a chemical pattern resembling that of common viruses, such as Epstein-Barr Virus (EBV), which affects over 85% of the population but has been implicated in prior research as a possible cause of multiple sclerosis.
A subset of MS patients exhibited additional indications of an immune war in their brains years prior to their diagnosis. Neurofilament light (Nfl), a protein released during neuronal breakdown, was found to be elevated in patients with these autoantibodies, according to research by co-author Ahmed Abdelhak, MD, a postdoctoral fellow in Ari Green, MD’s laboratory at UCSF.
Maybe friendly human proteins were being mistaken for a virus, the researchers surmised, which would explain why MS patients would live a lifetime with the disease.
“Everyone looks unique, with their own fingerprint of immunological experience, like a snowflake, when we analyze healthy people using our technology,” DeRisi said.
We start to suspect something is wrong when a person’s immunological signature stops looking like snowflakes and starts to resemble someone else, which is what we discovered in these MS patients. “.
a test designed to direct patients quickly to the best treatments.
The group examined blood samples from UCSF ORIGINS study participants to validate their results. All of these patients experienced neurological symptoms, and many of them—though not all of them—went on to receive an MS diagnosis.
Again, the same autoantibody pattern was found in 10% of patients with MS diagnosed in the ORIGINS study. There was no doubt that the pattern would lead to an MS diagnosis. Every patient exhibiting this autoantibody pattern in both the Department of Defense and ORIGINS groups also had multiple sclerosis.
“The lack of disease-specific biomarkers makes the diagnosis of multiple sclerosis (MS) not always simple,” Wilson stated. “Anything that can provide more diagnostic certainty early on and a tangible discussion about whether to start treatment for each patient excites us. “.
About ninety percent of MS patients do not yet know how the disease progresses, and there are many unanswered questions concerning the condition, including what triggers the immune response in some MS patients. However, the scientists think they have a clear indication that MS is developing now.
Senior author of the paper and director of the UCSF Weill Institute for Neurosciences Stephen Hauser, MD, said, “Imagine if we could diagnose MS before some patients reach the clinic.”. It increases the likelihood that we will progress from suppression to cure. “.
See the paper for funding and disclosures.
The other authors from UCSF are Kristen J., Rebecca D. Bair, and Ravi Dandekar. Wade, Rebecca Gomez, Asritha Tubati, Christopher M. Bartley, Camille Fouassier, Chloe Gerungan, Jessica Alexander, and Anne E. Rita P. Wapniarski. Loudermilk, Elizabeth L. Eggers, the Kelvin C. Sabrina A., Nora Jabassini, Kirtana Ananth, and Zorn. Mann; Adam Santaniello; Roland G.; Nicholas R. Ragan. Ernesto Henry, Jr. Andrew M. Baranzini, Scott S. Zamvil, Riley M. Bove, Chu-Yueh Guo, Jeffrey M. Gelfand, Richard Cuneo, H. -Christian von Büdingen, Bruce AC Cree, Jill A., and Jorge R. Oksenberg. Hollenbach as well as Ari J. Verdant. Refer to the paper for all authors.
regarding this news on multiple sclerosis research.
Levi Gadye wrote this.
The UCSF is the source.
Contact: UCSF’s Levi Gadye.
Photo credit: This image is courtesy of Neuroscience News.
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Michael Wilson et al.’s paper “An autoantibody signature predictive for multiple sclerosis”. Natural Medicine.
Inabst.
a multiple sclerosis predictive autoantibody signature.
There is still no reliable autoantibody for multiple sclerosis (MS), despite the fact that B cells are involved in the pathophysiology of the disease.
Whole-proteome autoantibody profiles of hundreds of MS patients (PwMS) both before and after the onset of the disease were created in this study using the Department of Defense Serum Repository (DoDSR), a cohort of over 10 million people.
By comparing the autoantibody signatures of about 10% of PwMS to a common motif shared by numerous human pathogens, this analysis identifies a distinct cluster.
Compared to other PwMS, these patients have higher serum neurofilament light (sNfL) levels and show antibody reactivity years before they experience symptoms of MS.
This profile is also long-lasting, offering molecular proof of an immunologically active preclinical stage that occurred years before clinical manifestation.
This autoantibody reactivity was confirmed in cerebrospinal fluid and serum samples from a different incident MS cohort, and it is highly specific for patients who are eventually diagnosed with MS.
This signature may be clinically useful as an antigen-specific biomarker for high-risk patients with clinically or radiologically isolated neuroinflammatory syndromes, and it serves as a foundation for future immunological characterization of this subset of MS patients.
