Predictive Value of BAFF in Secondary Autoimmunity and Immunodeficiency in Multiple Sclerosis Patients on B-cell Depletion Therapies
Arina Alexeeva1, Anastasia Chumakova1, Gaby Thai1, Michael Demetriou1, Michael Sy1
1University of California Irvine
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.
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