Rituximab as Monotherapy for Elicited Xenoreactive Antibody Responses

Abstract

This study was conducted in a non-human primate model to determine the impact of the rituximab, an anti-CD20 monoclonal antibody, as monotherapy on elicited xenoreactive antibody responses. Adult baboons were divided into 2 groups: Group 1 baboons were treated with rituximab then sensitized with porcine red blood cells; Group 2 baboons did not receive rituximab but were immunized with porcine red blood cells. Both groups were followed-up prospectively for 4 weeks. During this time, sera and peripheral lymphocytes were collected for analysis. Anti-galactose-alpha (Galalpha)-1-3 Gal-immunoglobulin (Ig) M and anti-IgG antibody titers were measured using porcine cell enzyme-linked immunosorbent assay, and flow-cytometry was used to study populations of B cells after rituximab therapy. After the administration of rituximab, baboons in Group 1 had a detectable decrease in the percent of CD19(+)/CD20(+) B cells. The effect of rituximab lasted for more than a month in this group. Despite the elimination of B cells, both groups developed vigorous anti-Galalpha-1-3 Gal antibody responses, which were evident within 12 days of immunizations. Furthermore, this increase in the anti-Galalpha-1-3 Gal antibody titers was accompanied by a relative rise in the percentage of double negative (CD19(-)/CD20(-)) but IgM(+) and IgG(+) B cells. In a non-human primate model of xenotransplantation, anti-Galalpha-1-3 Gal antibody responses were elicited despite the elimination of B cells by rituximab. These responses seem to be mediated in part by cells lacking common B-cell surface antigens.