Mogamulizumab Suppresses Induction of Myelin-Reactive Antibodies After Experimental Spinal Cord Injury

Traumatic spinal cord injury (SCI) is believed to increase the risk of autoimmune diseases, including the autoimmune demyelinating disease multiple sclerosis (MS), in humans. The adaptive immune response against one of the key MS autoantigens, myelin basic protein (MBP), is elevated in mice and persists in patients with SCI even 10 years after the initial injury. Here, we show that β1i-enriched immunoproteasomes and PA28β subunits are elevated as early as 12 h post-SCI in DA rats, and all proteasome catalytic immunosubunits are highly abundant in the injured spinal cord of DA and SD rats 7–14 days post-SCI; these changes may therefore represent a primary event of the adaptive myelin-reactive immune response. Mogamulizumab bound a recombinant rat CCR4 N-terminal extracellular fragment, albeit less strongly than the corresponding human fragment, and treatment was associated with weaker CCR4-associated immunoreactivity in peripheral blood leukocyte lysates. Plasma samples from rats with SCI treated with mogamulizumab were characterized by lower levels of antibodies to MBP compared with those from the non-treated group, and by day 60 of the experiment, this discrepancy reached statistical significance. Compared with non-treated animals, rats treated with mogamulizumab showed a significantly decreased glial scar size and total area of cyst-like cavities. Thus, mogamulizumab therapy not only improves the morphological features of the glial scar but also suppresses the autoimmune response against myelin, and may offer a complementary immunological strategy for spinal cord protection following injury.