Rituximab as monotherapy for elicited xenoreactive antibody responses
Rituximab as monotherapy for elicited xenoreactive antibody responses
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DOI：
10.1016/j.healun.2006.09.008
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发表时间：
2006-12-01
影响因子：
8.9
通讯作者：
Davis, R. Duane, Jr.
中科院分区：
文献类型：
--
作者：
Gonzalez-Stawinski, Gonzalo V.;Davis, R. Duane, Jr.
目的：本研究进行了非人灵长类动物模型，以确定利妥昔单抗，抗CD 20单克隆抗体，作为单一疗法对引起异种反应性抗体responses.Methods的影响：成年狒狒分为2组：第一组狒狒利妥昔单抗处理，然后用猪红细胞致敏;第2组狒狒没有接受利妥昔单抗，但用猪红细胞免疫。两组均前瞻性随访4周。在此期间，血清和外周血。收集淋巴细胞用于分析。用猪细胞酶联免疫吸附试验测定抗半乳糖-et（Ga α）-1-3 Gal-免疫球蛋白（IG）M和抗IgG抗体滴度，并用流式细胞术研究利妥昔单抗治疗后B细胞群。利妥昔单抗的效果在该组中持续了一个多月。尽管消除了B细胞，但两组都产生了强烈的抗Gal α-1-3 Gal抗体应答，这在免疫后12天内是明显的。此外，抗Gal α-1-3 Gal抗体滴度的这种增加伴随着a.双阴性（CD 19（-）/CD 20（-））但IgM（+）和IgG（+）B细胞百分比的相对上升。结论：在异种移植的非人灵长类动物模型中，尽管利妥昔单抗消除了B细胞，但仍引发了抗Gal α-1-3 Gal抗体应答。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。
Purpose: 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 I baboons were treated with rituximah 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-et (Ga alpha)-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 I 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-Gal alpha-1-3 Gal antibody responses, which were evident within 12 days of immunizations. Furthermore, this increase in the anti-Gal alpha-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-Gal alpha-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.