Abstract Details

Title B Cell Exchange across the Blood-Brain Barrier in Multiple Sclerosis

Topic MS and Related Diseases

Presentation(s) S11 - (-)

Poster/Presentation
Number 003

Objective

Background In multiple sclerosis (MS) pathogenic B cells likely act on both sides of the blood-brain barrier (BBB). It is unknown whether antigen-experienced B cells are shared between the central nervous system (CNS) and peripheral blood (PB) compartments in MS or OND patients.

Design/Methods We amplified IgG heavy chain variable region genes (IgG-VH) by 5'-RACE followed bey deep IgG-VH repertoire sequencing from paired cerebrospinal fluid (CSF) and PB samples from patients with MS (n=6) and other neurological diseases (OND; n=7)).

Results CSF IgG-VH transcripts could be amplified from all MS patients and from 4 of 7 OND samples. Accordingly, all 6 MS patients expressed IgG in their CSF, while 3 OND patients did not. Mean total IgG-VH sequencing reads were 22,395 (SD +/-10,118) from CSF and 399,966 (SD +/-113,192) from PBMC. We identified identical or related IgG-VH sequences in paired CSF and PBMC IgG-VH datasets of 5/6 MS patients and 3/4 OND patients. We show that restricted pools of clonally related B cells participate in robust bi-directional exchange across the BBB. In clusters of related IgG-VH we find evidence for active B cell diversification particularly in MS patients, either primarily in the CNS, or primarily in the PB, or in both compartments in parallel.

Conclusions B cells are strong candidates for autoimmune effector cells in MS, and these findings suggest that CNS-directed autoimmunity may be triggered and supported on both sides of the BBB. In MS and in other inflammatory states, these data also provide a powerful approach to identify and monitor B cells in the PB that correspond to clonally amplified populations in the CNS.

Authors/Disclosures
H.-Christian C. von Büdingen, MD, FAAN (F. Hoffmann-La Roche Ltd) PRESENTER	Dr. Von Buedingen has received personal compensation for serving as an employee of F. Hoffmann-La Roche Ltd.. Dr. Von Buedingen has received stock or an ownership interest from F. Hoffmann-La Roche Ltd.
	No disclosure on file
	No disclosure on file
Lisa Hobson-Webb, MD, FAAN (Duke University Medical Center)	An immediate family member of Dr. Hobson-Webb has received personal compensation for serving as an employee of G1 Therapeutics. Dr. Hobson-Webb has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Wiley Publishing. The institution of Dr. Hobson-Webb has received research support from Sanofi Genzyme.
	No disclosure on file
	No disclosure on file
	No disclosure on file
Bruce A. Cree, MD, PhD, MAS, FAAN (UCSF, Multiple Sclerosis Center)	The institution of Dr. Cree has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. The institution of Dr. Cree has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for EMD Serono. The institution of Dr. Cree has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. The institution of Dr. Cree has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sanofi. The institution of Dr. Cree has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for TG Therapeutics. The institution of Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Autobahn. The institution of Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Avotres. The institution of Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. Dr. Cree has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Horizon. Dr. Cree has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Neuron23. Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Boston Pharma. Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Hexal/Sandoz. Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Kyverna. Dr. Cree has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Immunic AG. The institution of Dr. Cree has received research support from Genentech. The institution of Dr. Cree has received research support from Kyverna. Dr. Cree has received publishing royalties from a publication relating to health care.
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Stephen L. Hauser, MD (UCSF Weill Institute for Neurosciences)	Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for NGM Bio. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Moderna. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BD. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Pheno Therapeutics. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Nurix Therapeutics. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Gilead. Dr. Hauser has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Accure. Dr. Hauser has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alector. Dr. Hauser has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Annexon. Dr. Hauser has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Hinge Therapeutics. Dr. Hauser has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for Neurona. Dr. Hauser has a non-compensated relationship as a Clinical Trial/Primary Investigator with Roche that is relevant to AAN interests or activities. Dr. Hauser has a non-compensated relationship as a Clinical Trial/Primary Investigator with Novartis that is relevant to AAN interests or activities.

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