Gonzalez-Stawinski Gonzalo V, Davis R Duane
Department of Thoracic and Cardiovascular Surgery, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
J Heart Lung Transplant. 2006 Dec;25(12):1462-6. doi: 10.1016/j.healun.2006.09.008. Epub 2006 Oct 30.
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.
本研究在非人类灵长类动物模型中进行，以确定抗CD20单克隆抗体利妥昔单抗作为单一疗法对引发的异种反应性抗体反应的影响。
成年狒狒分为两组：第1组狒狒先用利妥昔单抗治疗，然后用猪红细胞致敏；第2组狒狒未接受利妥昔单抗治疗，但用猪红细胞免疫。两组均进行前瞻性随访4周。在此期间，收集血清和外周淋巴细胞进行分析。使用猪细胞酶联免疫吸附测定法测量抗半乳糖-α（Galα）-1-3半乳糖免疫球蛋白（Ig）M和抗IgG抗体滴度，并使用流式细胞术研究利妥昔单抗治疗后B细胞群体。
给予利妥昔单抗后，第1组狒狒的CD19(+)/CD20(+) B细胞百分比明显下降。该组中利妥昔单抗的作用持续了一个多月。尽管B细胞被清除，但两组均产生了强烈的抗Galα-1-3半乳糖抗体反应，在免疫后12天内即可明显看出。此外，抗Galα-1-3半乳糖抗体滴度的这种增加伴随着双阴性（CD19(-)/CD20(-)）但IgM(+)和IgG(+) B细胞百分比的相对升高。
在异种移植的非人类灵长类动物模型中，尽管利妥昔单抗清除了B细胞，但仍引发了抗Galα-1-3半乳糖抗体反应。这些反应似乎部分由缺乏常见B细胞表面抗原的细胞介导。
