Rituximab as monotherapy for elicited xenoreactive antibody responses.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Gonzalez-Stawinski
Gonzalo V
GV
Department of Thoracic and Cardiovascular Surgery, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
Davis
R Duane
RD
D000818:Animals; D000910:Antibodies, Heterophile / Q000096:biosynthesis*; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D058846:Antibodies, Monoclonal, Murine-Derived; D018941:Antigens, CD19 / Q000378:metabolism; D018951:Antigens, CD20 / Q000378:metabolism; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D001773:Blood Cells / Q000276:immunology; D004187:Disaccharides / Q000276:immunology; D007114:Immunization; D023421:Models, Animal; D010215:Papio; D000069283:Rituximab; D013552:Swine / Q000097:blood*; D065227:Transfusion Reaction; D014183:Transplantation, Heterologous
D000910:Antibodies, Heterophile; D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018941:Antigens, CD19; D018951:Antigens, CD20; D004187:Disaccharides; C055075:galactosyl-(1-3)galactose; D000069283:Rituximab