Neutralizing BAFF/APRIL with atacicept prevents early DSA formation and AMR development in T cell depletion induced nonhuman primate AMR model.
Neutralizing BAFF/APRIL with atacicept prevents early DSA formation and AMR development in T cell depletion induced nonhuman primate AMR model.
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用ATACICEPT中和BAFF/4月可以防止T细胞耗竭诱导的非人类灵长类动物AMR模型中的早期DSA形成和AMR发展。
DOI：
10.1111/ajt.13045
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发表时间：
2015-03
期刊：
影响因子：
--
通讯作者：
Knechtle S
中科院分区：
文献类型：
--
作者：
Kwun J;Page E;Hong JJ;Gibby A;Yoon J;Farris AB;Villinger F;Knechtle S
在器官移植中，旨在实现诱导耐受的耗竭策略与抗体介导的排斥反应(AMR)和移植物损伤的发生率和风险增加相关。我们的临床数据表明，在接受阿伦珠单抗治疗的患者中，血清B细胞激活因子/生存因子(BAFF)的增加与抗体介导的排斥反应风险的增加有关。在本研究中，我们在非人灵长类AMR模型中测试了BAFF阻断(TACI-Ig)预防同种异体抗体产生和延长同种异体移植物存活的能力。3只动物接受AMR诱导方案(CD3-IT/alefacept/他克莫司)和TACI-Ig(Atacicept)，与只接受AMR诱导方案的5只对照动物相比。在移植后2周和4周，Taci-Ig治疗导致治疗动物的DSA水平降低(p<；0.05)。此外，移植后6周，外周血B细胞数量显著减少。然而，移植肾存活率仅有轻微增加(59±22天vs.102±47天；p=0.11)。组织学分析显示，使用阿替西普治疗后，通常与体液排斥相关的发现显著减少。在阿替西普治疗中，随着移植物T细胞浸润的增加，观察到更多的T细胞排斥反应，这可能是移植物延长的继发原因。我们表明，在我们的耗竭诱导的临床前AMR模型中，BAFF/APRLE阻断结合TACI-Ig治疗减少了排斥反应的体液部分。
Depletional strategies directed toward achieving tolerance induction in organ transplantation have been associated with an increased incidence and risk of antibody-mediated rejection (AMR) and graft injury. Our clinical data suggest correlation of increased serum B cell activating factor/survival factor (BAFF) with increased risk of antibody-mediated rejection in alemtuzumab treated patients. In the present study, we tested the ability of BAFF blockade (TACI-Ig) in a nonhuman primate AMR model to prevent alloantibody production and prolong allograft survival. Three animals received the AMR inducing regimen (CD3-IT/alefacept/tacrolimus) with TACI-Ig (atacicept), compared to five control animals treated with the AMR inducing regimen only. TACI-Ig treatment lead to decreased levels of DSA in treated animals at 2 and 4 weeks posttransplantation (p < 0.05). In addition, peripheral B cell numbers were significantly lower at 6 weeks posttransplantation. However, it provided only a marginal increase in graft survival (59 ± 22 vs. 102 ± 47 days; p = 0.11). Histological analysis revealed a substantial reduction in findings typically associated with humoral rejection with atacicept treatment. More T cell rejection findings were observed with increased graft T cell infiltration in atacicept treatment, likely secondary to the graft prolongation. We show that BAFF/APRIL blockade using concomitant TACI-Ig treatment reduced the humoral portion of rejection in our depletion-induced preclinical AMR model.
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影响因子：
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作者：
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影响因子：
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作者：
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DOI：
10.1111/ajt.12526
发表时间：
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期刊：
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
影响因子：
--
作者：
Kim EJ;Kwun J;Gibby AC;Hong JJ;Farris AB 3rd;Iwakoshi NN;Villinger F;Kirk AD;Knechtle SJ
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Knechtle SJ
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