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Selective depletion of plasma cells in vivo based on the specificity of their secreted antibodies.
European Journal of Immunology ( IF 4.5 ) Pub Date : 2019-11-12 , DOI: 10.1002/eji.201948144
Qingyu Cheng 1, 2 , Andreas Pelz 1, 2 , Adriano Taddeo 1 , Laleh Khodadadi 1, 2 , Jens Klotsche 1 , Bimba F Hoyer 1, 2 , Tobias Alexander 1, 2 , Andreas Thiel 3 , Gerd-R Burmester 2 , Andreas Radbruch 1 , Falk Hiepe 1, 2
Affiliation  

Antibody-mediated diseases affect more than 10% of the human population. For most, no cure is available, particularly when the pathogenic antibodies are secreted by long-lived plasma cells resistant to conventional immunosuppressive therapies. Current therapeutic approaches target not only the plasma cells that secrete pathogenic antibodies, but also those providing protective antibodies. Here, in a murine model bearing long-lived plasma cells secreting anti-OVA and -chicken gamma globulin (CGG) antibodies, we describe the first-time use of an antigen-antibody (OVA/anti-CD138 antibody) conjugate for in vivo labeling and selective ablation of plasma cells that secrete antibodies specific for the antigen OVA. The selective depletion also led to a stable reduction of the corresponding serum anti-OVA antibody levels. In contrast, CGG-specific plasma cells and circulating anti-CGG antibody levels remained unchanged. The method described here should enable the development of unique causative treatment strategies for established antibody-mediated diseases sparing humoral immunity.

中文翻译:

根据体内分泌的抗体的特异性选择性清除体内浆细胞。

抗体介导的疾病影响了超过10%的人口。大多数情况下,无法治愈,特别是当病原性抗体由对常规免疫抑制疗法有抵抗力的长寿浆细胞分泌时。当前的治疗方法不仅靶向分泌病原性抗体的浆细胞,而且靶向提供保护性抗体的浆细胞。在这里,在携带分泌抗-OVA和-鸡γ球蛋白(CGG)抗体的长寿浆细胞的小鼠模型中,我们描述了抗原-抗体(OVA /抗-CD138抗体)结合物在体内的首次使用分泌特异于抗原OVA的抗体的浆细胞的标记和选择性消融。选择性消耗还导致相应血清抗OVA抗体水平的稳定降低。相比之下,CGG特异性浆细胞和循环的抗CGG抗体水平保持不变。此处描述的方法应能够为建立的不介体液免疫的抗体介导的疾病开发独特的病因治疗策略。
更新日期:2019-11-20
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