Differential Effects of MS Therapeutics on B Cells—Implications for Their Use and Failure in AQP4-Positive NMOSD Patients

Abstract

B cells are considered major contributors to multiple sclerosis (MS) pathophysiology. While lately approved disease-modifying drugs like ocrelizumab deplete B cells directly, most MS medications were not primarily designed to target B cells. Here, we review the current understanding how approved MS medications affect peripheral B lymphocytes in humans. These highly contrasting effects are of substantial importance when considering these drugs as therapy for neuromyelitis optica spectrum disorders (NMOSD), a frequent differential diagnosis to MS, which is considered being a primarily B cell- and antibody-driven diseases. Data indicates that MS medications, which deplete B cells or induce an anti-inflammatory phenotype of the remaining ones, were effective and safe in aquaporin-4 antibody positive NMOSD. In contrast, drugs such as natalizumab and interferon-β, which lead to activation and accumulation of B cells in the peripheral blood, lack efficacy or even induce catastrophic disease activity in NMOSD. Hence, we conclude that the differential effect of MS drugs on B cells is one potential parameter determining the therapeutic efficacy or failure in antibody-dependent diseases like seropositive NMOSD.

Progress in treatment of neuromyelitis optica spectrum disorders (NMOSD): Novel insights into therapeutic possibilities in NMOSD

“…Generally, B‐cell subpopulation with CD19(int), CD27(high), and CD38(high) phenotypes produced AQP4‐IgG in NMOSD patients and obviously enhanced in the peripheral blood during relapse of disease 61 . There's no doubt that B cells had contributed to the pathogenesis of NMOSD, which has confirmed by the growing evidence 62,63 …”

COVID-19 Vaccination and The Eye

“…Overall, the onset of symptoms two weeks following immunisation could potentially be consistent with a dysimmunological process, although it remains uncertain whether this might have been partially attributed to the intended B lymphocyte response targeting the adenovirus vector vaccine, or further exacerbated by the activation and accumulation of B lymphocytes in the peripheral blood incited by natalizumab. 51,53 The second case occurred in a patient who developed MOG antibody-associated bilateral anterior optic neuritis and concurrent subacute thyroiditis, with symptom onset 6 weeks following the first dose and 12 hours after receiving the second dose of the inactivated virus CoronaVac (Sinovac) vaccine. 52 The patient was examined 5 days following symptom onset and demonstrated bilateral optic disc swelling, positive anti-MOG IgG, elevated thyroid stimulating hormone (TSH), antithyroglobluin, anti-thyroid peroxidase, but normal thyroxine levels.…”

Acute bilateral optic/chiasm neuritis with longitudinal extensive transverse myelitis in longstanding stable multiple sclerosis following vector-based vaccination against the SARS-CoV-2

“…NAT usually leads to activation and accumulation of B cells in the peripheral blood but prevents immune cells from crossing the (intact) blood–brain barrier. NAT could have induced catastrophic disease activity in this AQP4-ab negative NMOSD-like syndrome [ 8 ]. However, as this had not occurred during 10 years of regular NAT treatment, NAT is unlikely to be the cause for the acute LETM.…”