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 24h 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.