Antibody-mediated immunosuppression can result from RBC antigen loss independent of Fcγ receptors in mice
Antibody-mediated immunosuppression can result from RBC antigen loss independent of Fcγ receptors in mice
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DOI：
10.1111/trf.14939
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发表时间：
2019-01-01
期刊：
影响因子：
2.9
通讯作者：
Stowell, Sean R.
中科院分区：
文献类型：
--
作者：
Mener, Amanda;Patel, Seema R.;Stowell, Sean R.
背景技术背景：抗RhD给药可预防RhD+红细胞（RBC）暴露后重新形成抗RhD，称为抗体介导的免疫抑制（AMIS）。最近的研究表明，AMIS可能通过靶抗原改变（称为抗原调节）发生。然而，研究表明AMIS可能不依赖于抗原调节而发生。特别地，转基因表达融合鸡蛋溶菌酶-卵清蛋白-达菲（HOD）抗原的RBC的AMIS已经显示独立于被认为是抗原调节所需的活化Fc γ受体（Fc γ R）而发生。因此，我们试图确定HOD RBC暴露后AMIS背后的机制。研究设计和方法：在存在或不存在单克隆抗鸡蛋溶菌酶（HEL）抗体的情况下，将HOD RBC转移到野生型或Fc γ R链敲除受体中后，单独或组合地，检查HOD抗原水平和抗HOD抗体形成。我们的结果表明，抗HEL抗体单独或组合抑制抗HOD IgM，这与HOD RBC上HEL的可检测降低速率相关。此外，单独或组合暴露于抗HEL抗体同样抑制抗HOD IgG形成。出乎意料的是，组合或单独的抗HEL抗体以Fc γ R非依赖性方式诱导AMIS和抗原调节。HOD RBC暴露于抗HEL抗体可降低抗原水平并抑制HOD RBC暴露后的抗HOD抗体形成。结论：这些结果表明，抗体介导的抗原调节可能反映了AMIS的一种机制，这种机制可以独立于激活Fc γ R而发生，并可能提供一种替代物来鉴定能够诱导针对不同RBC抗原的AMIS的抗体。
BACKGROUND: Anti-RhD administration can prevent de novo anti-RhD formation following RhD+ red blood cell (RBC) exposure, termed antibody-mediated immunosuppression (AMIS). Recent studies suggest that AMIS may occur through target antigen alterations, known as antigen modulation. However, studies suggest that AMIS may occur independent of antigen modulation. In particular, AMIS to RBCs that transgenically express the fusion hen egg lysozyme-ovalbumin-Duffy (HOD) antigen have been shown to occur independent of activating Fc gamma receptors (Fc gamma Rs) thought to be required for antigen modulation. Therefore, we sought to determine the mechanism behind AMIS following HOD RBC exposure.STUDY DESIGN AND METHODS: Following transfer of HOD RBCs into wild-type or Fc gamma R-chain knockout recipients in the presence or absence of monoclonal anti-hen egg lysozyme (HEL) antibody, individually or in combination, HOD antigen levels and anti-HOD antibody formation were examined.RESULTS: Our results demonstrate that anti-HEL antibodies individually or in combination suppressed antiHOD IgM, which correlated with the rate of detectable decrease in HEL on HOD RBCs. Furthermore, exposure to anti-HEL antibodies alone or in combination equally suppressed anti-HOD IgG formation. Unexpectedly, combination or individual anti-HEL antibodies induced AMIS and antigen modulation in an Fc gamma R-independent manner. Pre-exposure of HOD RBCs to anti-HEL antibodies reduced antigen levels and suppressed antiHOD antibody formation following HOD RBC exposure.CONCLUSION: These results suggest that antibodymediated antigen modulation may reflect a mechanism of AMIS that can occur independent of activating Fc gamma Rs and may provide a surrogate to identify antibodies capable of inducing AMIS against different RBC antigens.