B-Cell Depletion with CD20 Antibodies as New Approach in the Treatment of Inflammatory and Immunological Events Associated with Spinal Cord Injury

Abstract

Spinal cord injury (SCI) is a highly debilitating pathology that has irreversible impacts and results in functional loss. We evaluated the anti-inflammatory and immunologic role of antibody-mediated depletion of B cells through the glycoengineered anti-muCD20 antibody (18B12) in an experimental model of spinal cord compression, in vivo and ex vivo. Intraperitoneal 18B12 was administered at a dose of 30 mg/kg, 1 h and 6 h after SCI, and mice were sacrificed 24 h after trauma. We demonstrated, in vivo, that 18B12 slowed severe hindlimb motor dysfunction (Basso Mouse Scale score) and neuronal death by histological evaluation in SCI mice, as well as decreased expression of nuclear factor-kB, inducible nitric oxide synthase, cytokines, and glial fibrillary acidic protein. Also, 18B12 reduced expression of microglia, just as it lowered the expression of B and T lymphocytes. Moreover, in spinal cord organotypic cultures, pretreatment with 18B12 significantly reduced nitric oxide expression and protected cells from cell death [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay]. In this study, we showed that 18B12 treatment reduces the development of inflammation and tissue injury by alteration of the immune system associated with SCI. This study increases the current knowledge that B-cell depletion is able to exert immunomodulating actions in damaged spinal cords.

Potential immunotherapies for traumatic brain and spinal cord injury

“… 220 Antibody-mediated depletion of B cells through the glycoengineered anti-muCD20 antibody (18B12) in a mouse model significantly inhibits the NFκB-dependent production of pro-inflammatory mediators and improves functional recovery after SCI. 221 The therapeutic CD20 antibodies such as rituximab or obinutuzumab may provide a new immunotherapy for the treatment of CNS injury.…”

Obinutuzumab-Induced B Cell Depletion Reduces Spinal Cord Pathology in a CD20 Double Transgenic Mouse Model of Multiple Sclerosis

“…depleted B cells using 18B12 in a murine model of spontaneous autoimmune thyroiditis in young mice to show that the following activation of regulatory T cells inhibited development of the disease in adult mice [ 37 ]. Casili et al showed that 18B12 treatment lessened inflammation and tissue damage in a model of spinal cord injury [ 38 ].…”

Treatment of spinal cord injury with mesenchymal stem cells

“…Research conducted on a rodent SCI model indicated that antibodies targeting myelin-associated inhibitors could increase the locomotor function after injury [ 92 ]. Another study administered B-cell-depleting antibodies to control injury-associated inflammation and the treatment was found to subside the inflammation, promote cell survival and reduce hindlimb dysfunction [ 93 ]. Thus, the combination of immunotherapy and MSC treatment may be more effective in treating SCI by suppressing the inflammation and promoting cord regeneration.…”