Comprehensive analysis of B cell repopulation in ocrelizumab-treated patients with multiple sclerosis by mass cytometry and proteomics

Product:

Inflammation Panel 250

Topic:

Neurology

Disease Area:

Multiple Sclerosis (MS)

Sample Type:

Plasma

Topic/Product:

Inflammation Panel 250

Disease Area:

Multiple Sclerosis (MS)

Sample Type:

Plasma

Highlights

aCD20 therapy associated with a reduction of memory T cells and activated myeloid cells
CD20⁺ naive B cells with a transitional phenotype was majority of repopulating B cells
Plasma TNFRSF13B, TNFRSF13C, TNFRSF9, TNFSF9, and CXCL13 were declined after aCD20 therapy
Plasma level of TNFRSF13C was strongly associated with B cell repopulation

Summary

Ocrelizumab, an anti-CD20 antibody, depletes CD20⁺ B cells, which subsequently repopulate over months. Little is known about changes in other immune cell populations and molecular markers associated with B cell repopulation. Here, we performed a comprehensive characterization of immune cells from ocrelizumab-treated patients with multiple sclerosis (MS) using mass cytometry. About 50% of patients showed naive B cell repopulation after 6 months mainly with a transitional phenotype, whereas CD27⁺ memory B cells only rarely repopulated. This repopulation was associated with a reduction of memory T cells and activated myeloid cells, as well as reduced expression of activation/migration markers in both cell types. A plasma proteomics analysis identified proteins including TNFRSF13C, associated with B cell depletion and repopulation. Plasma levels of neurofilament light-chain protein declined after ocrelizumab treatment was not linked with B cell repopulation. These findings identify potential soluble markers for monitoring of ocrelizumab treatment in MS.

Authors & Affiliations

Meng Wang,1,2,3,8 Carolin Otto,4,8 Camila Ferna ´ndez Zapata,1,2,3 Adeline Dehlinger,1,2,3 Gerardina Gallaccio,1,2,3 Lisa-Marie Diekmann,1,2,3 Moritz Niederschweiberer,4 Patrick Schindler,1,2,3,4,5 Peter Ko¨rtve´lyessy,6 Desiree Kunkel,7 Friedemann Paul,1,2,3,4,5,9 Klemens Ruprecht,4,9 and Chotima Boettcher 1,2,3,9,10,*

Experimental and Clinical Research Center, a Cooperation between the Max Delbru ¨ck Center for Molecular Medicine in the Helmholtz Association and Charite ´ Universita ¨tsmedizin Berlin, Berlin, Germany
Charite ´ – Universita¨tsmedizin Berlin, Corporate Member of Freie Universita ¨t Berlin and Humboldt-Universita ¨t zu Berlin, Experimental and Clinical Research Center, Lindenberger Weg 80, Berlin 13125, Germany
Max Delbru ¨ck Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany
Department of Neurology with Experimental Neurology, Charite ´ – Universita ¨tsmedizin Berlin, Corporate Member of Freie Universita ¨t Berlin and Humboldt-Universita ¨t zu Berlin, Berlin 10117, Germany
Neuroscience Clinical Research Center, Charite ´ – Universita ¨tsmedizin Berlin, Corporate Member of Freie Universita¨t Berlin and Humboldt-Universita¨t zu Berlin, Berlin 10117, Germany
Department of Neurology, Center for ALS and Other Motor Neuron Disorders, Charite ´ – Universita ¨tsmedizin Berlin, Corporate Member of Freie Universita ¨t Berlin, Humboldt-Universita ¨t zu Berlin, and Berlin Institute of Health, Berlin, Germany
Flow & MassCytometry Core Facility, Berlin Institute of Health at Charite ´ – Universita ¨tsmedizin Berlin, Berlin 13353, Germany

Steve Williams, MD, PhD

CSO

Dr. Willams serves as the company’s Chief Scientific Officer. He was previously Chief Medical Officer at Standard Biotools and at SomaLogic where he pioneered the discipline for discovery and validation of predictive, diagnostic and prognostic models using machine-learning applied to large-plex proteomics. 20 such tests were used for drug characterization, safety and efficacy when incorporated in clinical drug trials at Pharma/Biotech and 17 different multivariate tests were validated and translated into regulated healthcare uses. Prior to SomaLogic, Dr. Williams was at Pfizer in the UK and the USA as a clinical triallist in Translational Medicine, and subsequently as VP, Global Clinical Technology. He sat on the National Advisory Council for the National Institute of Biomedical Imaging and Bioengineering, the Executive Committee for the FNIH Biomarkers Consortium, and worked with FDA and PhRMA on developing evidentiary standards for biomarker qualification. Dr. William’s medical training was in London, at Charing Cross and Westminster Medical School, followed by a PhD in medicine/physiology at the same institution and training in Radiology at the University of Newcastle Upon Tyne. Steve is co-inventor on 26 proteomics patents and author/coauthor on multiple foundational proteomics manuscripts.

Justin McAnear

CFO

Mr. McAnear serves as the company’s Chief Financial Officer. He brings over 25 years of operational and financial leadership experience across various sectors and was instrumental in taking 10x Genomics public in 2019, serving as its CFO for over five years. Mr. McAnear served for over 3 years as Tesla’s VP of Worldwide Finance and Operations, supporting landmark initiatives such as the Model X and Model 3 launches and Solar City acquisition. He also held various roles at Apple and J&J earlier in his career and served as a naval officer and aviator for over 9 years.