A Predictive Autoantibody Signature in Multiple Sclerosis
Author:
Zamecnik Colin R.ORCID, Sowa Gavin M., Abdelhak Ahmed, Dandekar Ravi, Bair Rebecca D., Wade Kristen J., Bartley Christopher M., Tubati Asritha, Gomez Refujia, Fouassier Camille, Gerungan Chloe, Alexander Jessica, Wapniarski Anne E., Loudermilk Rita P., Eggers Erica L., Zorn Kelsey C., Ananth Kirtana, Jabassini Nora, Mann Sabrina A., Ragan Nicholas R., Santaniello Adam, Henry Roland G., Baranzini Sergio E., Zamvil Scott S., Bove Riley M., Guo Chu-Yueh, Gelfand Jeffrey M., Cuneo Richard, von Büdingen H.-Christian, Oksenberg Jorge R., Cree Bruce AC, Hollenbach Jill A., Green Ari J., Hauser Stephen L., Wallin Mitchell T., DeRisi Joseph L., Wilson Michael R.ORCID
Abstract
AbstractAlthough B cells are implicated in multiple sclerosis (MS) pathophysiology, a predictive or diagnostic autoantibody remains elusive. Here, 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 of PwMS that 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 prodromal period years before clinical onset. This autoantibody reactivity was validated in samples from a separate incident MS cohort in both cerebrospinal fluid (CSF) 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.
Publisher
Cold Spring Harbor Laboratory
Cited by
4 articles.
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