Abstract Details

Title Analysis of B Cell Subsets in Multiple Sclerosis Patients on Immunomodulatory Therapy Reveals Modulation of CD19+CD24hiCD38hi Cells with Implications for the Diagnosis and Monitoring of MS

Topic MS and Related Diseases

Presentation(s) P03 - (-)

Poster/Presentation
Number 224

Objective

Background BACKGROUND: There are currently no serologic tests that aid in the selection or monitoring of therapy in RRMS. The role of B-cells in RRMS remains unclear.

Design/Methods DESIGN/METHODS: We recruited 13 patients (IFN? = 7, GA = 6) from the Stanford MS Center who met the following criteria: 1) age 20-45, 2) diagnosis of RRMS for less than 7 years, 3) clinically stable at the time of blood draw. We conducted ELISA for plasma BAFF levels and FACS for B-cell subsets. In EAE, we assessed BAFF levels, B-cell phenotypes, and disease in wild-type (WT) and muMT (B-cell deficient) mice treated with IFN?.

Results RESULTS: In patients, there was a trend towards increased BAFF in serum in patients treated with IFN? compared to GA. There was a significant increase in circulating B-cells (p < 0.005) and CD24hiCD38hi transitional B-cells (p < 0.001) in IFN? compared to GA. In EAE mice, rmIFN? treatment significantly increase in CD19+ B cells (n=3, p < 0.05) and serum BAFF levels (n = 5, p = 0.003) in IFN? compared to PBS controls. muMT mice developed EAE, but in contrast to WT animals did not respond to IFN? (n=3 per group).

Conclusions CONCLUSIONS: These data suggest mechanism of IFN? therapy is expanding transitional B-cells populations which may have regulatory effects in MS. The importance of B-cells was confirmed in EAE, where B-cells are necessary for successful IFN? therapy. This study has implications for the monitoring and treatment of recently diagnosed RRMS patients.

Authors/Disclosures
PRESENTER	No disclosure on file
Brigitte Wildemann, MD (University Hospital Heidelberg, Department of Neurology)	The institution of Dr. Wildemann has received research support from Roche. The institution of Dr. Wildemann has received research support from Novartis. The institution of Dr. Wildemann has received research support from Argenx. Dr. Wildemann has received personal compensation in the range of $500-$4,999 for serving as a Conference participant with Neuraxpharm. Dr. Wildemann has received personal compensation in the range of $0-$499 for serving as a Speaker with Roche. Dr. Wildemann has received personal compensation in the range of $0-$499 for serving as a Soeaker with Instand.
Alexandra L. Goodyear, MD (Genentech)	Dr. Goodyear has received personal compensation for serving as an employee of Genentech. Dr. Goodyear has received personal compensation for serving as an employee of Novartis. Dr. Goodyear has stock in Novartis. Dr. Goodyear has stock in Genentech.
	No disclosure on file
	No disclosure on file
Lawrence Steinman, MD, FAAN (Stanford Medicine)	Dr. Steinman has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for TG Therapeutics. Dr. Steinman has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for 180 Life Sciences. Dr. Steinman has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for BioAtla. Dr. Steinman has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for Pasithea. Dr. Steinman has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for Atreca. Dr. Steinman has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for Wilmer Hale Cutler Pickering. Dr. Steinman has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Bristol Meyers Squibb. Dr. Steinman has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for TG Therapeutics. Dr. Steinman has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for National Academy of Sciences. Dr. Steinman has received personal compensation in the range of $100,000-$499,999 for serving as an Expert Witness for Gibson Dunn. The institution of Dr. Steinman has received research support from Roche. The institution of Dr. Steinman has received research support from Novartis. Dr. Steinman has received intellectual property interests from a discovery or technology relating to health care.
Jeffrey E. Dunn, MD, FAAN (Stanford University Medical Center)	Dr. Dunn has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genentech. Dr. Dunn has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genzyme. The institution of Dr. Dunn has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Progentec Diagnostics. Dr. Dunn has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Kyverna Therapeutics. Dr. Dunn has received intellectual property interests from a discovery or technology relating to health care.
	No disclosure on file

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