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.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1038/s41591-024-02938-3 | DOI Listing |
Clin Exp Rheumatol
December 2024
Division of Rheumatology, Azienda Sanitaria Universitaria del Friuli Centrale, Santa Maria della Misericordia Hospital, Udine; and Department of Medicine (DMED), University of Udine, Italy.
Objectives: To characterise the overlap syndrome between Sjögren's disease (SjD) and systemic lupus erythematosus (SLE).
Methods: Consecutive patients clinically defined as affected by SjD and SLE overlap syndrome (SjD-SLE), belonging to two Italian rheumatology centres were classified following the application of both the SjD and SLE classification criteria. Clinical, functional, ultrasound and histological data were compared with patients suffering from only SjD or SLE.
Exp Cell Res
December 2024
Biophysics and Structural Genomics Division, Saha Institute of Nuclear Physics, A CI of Homi Bhabha National Institute, Kolkata, 700 064, West Bengal, India. Electronic address:
The signaling pathways behind severe astrocytic lysis with Aquaporin4 auto-antibody (AQP4-IgG) seropositivity, and reactive astrocytosis with myelin oligodendrocyte glycoprotein auto-antibody (MOG-IgG) seropositivity, remain largely unexplored in Neuromyelitis optica spectrum disorder (NMOSD), while almost no molecular details being known about double-seronegative (DN) patients. Recent discovery of glial fibrillary acidic protein (GFAP) in DN NMOSD patients' cerebrospinal fluid, akin to AQP4-IgG + ve cases, suggests astrocytopathy. Here, we aim to study small non coding RNA (sncRNA) signature alterations in astrocytes exposed to AQP4-IgG + ve and MOG-IgG + ve patient sera, and their potential resemblance with DN-NMOSD.
View Article and Find Full Text PDFbioRxiv
November 2024
Department of rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
Systemic Lupus Erythematosus (SLE) is an autoimmune disease characterized by an array of autoantibodies, in particular anti-nuclear antibodies (ANA). The disease is also hallmarked by an expansion of plasmablasts (PB) in peripheral blood. How these relate to autoantibody production is not clear.
View Article and Find Full Text PDFSci Rep
November 2024
Section for Immunology, Division of Infection Control, Norwegian Institute of Public Health, Oslo, Norway.
Disrupted cytokine networks and autoantibodies play an important role in the pathogenesis of systemic lupus erythematosus. However, conflicting reports and non-reproducibility have hindered progress regarding the translational potential of cytokines in SLE. This study attempts to address the existing knowledge gap using multiplex cytokine assay and machine learning.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!