Abstract Details

Title Predictive Value of BAFF in Secondary Autoimmunity and Immunodeficiency in Multiple Sclerosis Patients on B-cell Depletion Therapies

Topic Multiple Sclerosis

Presentation(s) P4 - Poster Session 4 (8:00 AM-9:00 AM)

Poster/Presentation
Number 19-003

Objective

We previously established B-cell activating factor (BAFF) as a biomarker of hypogammaglobinemia in Multiple Sclerosis (MS) patients on ocrelizumab. In this study, we investigate whether BAFF correlates with rates of secondary autoimmunity and immunodeficiency in MS patients on B-cell depleting therapies.

Background It is known that B-cell depleting therapies in MS patients have been associated with the development of secondary immunodeficiency and autoimmunity. Complications such as hypogammaglobinemia, with consequent infectious sequelae, inflammatory bowel disease (IBD), endocrinopathies, and psoriasis are most recognized. As biomarkers take the stage in MS clinical care - with potential to provide insight into disease pathogenesis and track treatment response - their relationship with B-cell depleting therapies is becoming increasingly relevant.

Design/Methods We explored a database of 365 MS patients who received Octave Biosciences Inc Multiple Sclerosis Disease Activity (MSDA) testing at UC Irvine between June 2023 and June 2024. We selected 42 MS patients with significantly elevated BAFF above 15 pg/mL (BAFF-superresponders), all of whom were on anti-CD20 treatments or status post autologous stem cell transplant at the time of testing. We used propensity matching to select 38 control patients with BAFF below 15 pg/ml. Clinical and laboratory data were retrospectively collected.

Results BAFF-superresponders were found to have higher rates of autoimmune complications and immunodeficiency compared with their age and treatment-matched controls (OR 3.4, 95% CI 1.27–9.1). Among the BAFF-superresponder group, 31% had hypogammaglobinemia (OR 3.8, 95% CI: 1.10–13.0), 10% autoimmune colitis, 7% organizing pneumonia, and 4% had other autoimmune diseases. In comparison, patients with BAFF below 15 pg/mL had no instances of autoimmune colitis or organizing pneumonia. Furthermore, BAFF-superresponders had increased rates of infections requiring hospitalization compared to the control group.

Conclusions These findings suggest that BAFF may serve as a sensitive and specific predictive marker for these complications in MS patients on anti-CD20 treatments.

Authors/Disclosures
Michael Y. Sy, MD, PhD (University of California, Irvine) PRESENTER	Dr. Sy has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech. Dr. Sy has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Octave Bioscience. Dr. Sy has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amgen. Dr. Sy has received personal compensation in the range of $500-$4,999 for serving as a Consultant for TG Therapeutics. Dr. Sy has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. Dr. Sy has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Alexion. Dr. Sy has received intellectual property interests from a discovery or technology relating to health care.
Arina Alexeeva, MD	Dr. Alexeeva has nothing to disclose.
Anastasia Chumakova, MD (UCI Medical Center)	Dr. Chumakova has nothing to disclose.
Gaby T. Thai, MD, FAAN (UC Irvine)	Dr. Thai has nothing to disclose.
Michael Demetriou, MD, PhD	Dr. Demetriou has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bristol Myers Squibb. Dr. Demetriou has stock in GlyTR Therapeutics. Dr. Demetriou has received intellectual property interests from a discovery or technology relating to health care.

��ɫ��

��ɫ��