Longitudinally persistent cerebrospinal fluid B-cells resist treatment in multiple sclerosis
Longitudinally persistent cerebrospinal fluid B-cells resist treatment in multiple sclerosis
Abstract B-cells are key contributors to chronic autoimmune pathology in multiple sclerosis (MS). Clonally related B-cells exist in the cerebrospinal fluid (CSF), meninges, and central nervous system (CNS) parenchyma of MS patients. Longitudinally stable CSF oligoclonal band (OCB) antibody patterns suggest some local CNS B-cell persistence; however, the longitudinal B-cell dynamics within and between the CSF and blood remain unknown. We sought to address this by performing immunoglobulin heavy chain variable region repertoire sequencing on B-cells from longitudinally collected blood and CSF samples of MS patients (n=10). All patients were untreated at the time of the initial sampling; the majority (n=7) were treated with immune modulating therapies 1.2 (+/?0.3 SD) years later during the second sampling. We found clonal persistence of B-cells in the CSF of five patients; these B-cells were frequently immunoglobulin (Ig) class-switched and CD27+. We identified specific blood B-cell subsets that appear to provide input into CNS repertoires over time. We demonstrate complex patterns of clonal B-cell persistence in CSF and blood, even in patients on high-efficacy immune modulating therapy. Our findings support the concept that peripheral B-cell activation and CNS-compartmentalized immune mechanisms are in part therapy-resistant.
Greenfield Ariele L.、Ramesh Akshaya、Laurent Sarah、Henry Roland G.、Bischof Antje、Hauser Stephen L.、Wilson Michael R.、von B¨1dingen H.-Christian、Weber Martin S.、Cree Bruce A.C.、Eggers Erica L.、Harkin William、Dandekar Ravi、Wu Hao、Pierson Natalie S.
UCSF Weill Institute for Neurosciences, Department of Neurology, University of CaliforniaUCSF Weill Institute for Neurosciences, Department of Neurology, University of CaliforniaUCSF Weill Institute for Neurosciences, Department of Neurology, University of CaliforniaUCSF Weill Institute for Neurosciences, Department of Neurology, University of CaliforniaUCSF Weill Institute for Neurosciences, Department of Neurology, University of CaliforniaUCSF Weill Institute for Neurosciences, Department of Neurology, University of CaliforniaUCSF Weill Institute for Neurosciences, Department of Neurology, University of CaliforniaUCSF Weill Institute for Neurosciences, Department of Neurology, University of CaliforniaInstitute of Neuropathology, Department of Neurology, University Medical Center G?ttingenUCSF Weill Institute for Neurosciences, Department of Neurology, University of CaliforniaUCSF Weill Institute for Neurosciences, Department of Neurology, University of CaliforniaUCSF Weill Institute for Neurosciences, Department of Neurology, University of CaliforniaUCSF Weill Institute for Neurosciences, Department of Neurology, University of CaliforniaUCSF Weill Institute for Neurosciences, Department of Neurology, University of CaliforniaUCSF Weill Institute for Neurosciences, Department of Neurology, University of California
神经病学、精神病学基础医学医学研究方法
Greenfield Ariele L.,Ramesh Akshaya,Laurent Sarah,Henry Roland G.,Bischof Antje,Hauser Stephen L.,Wilson Michael R.,von B¨1dingen H.-Christian,Weber Martin S.,Cree Bruce A.C.,Eggers Erica L.,Harkin William,Dandekar Ravi,Wu Hao,Pierson Natalie S..Longitudinally persistent cerebrospinal fluid B-cells resist treatment in multiple sclerosis[EB/OL].(2025-03-28)[2025-08-02].https://www.biorxiv.org/content/10.1101/490938.点此复制
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