新型血浆细胞靶向疗法或有效改善肾脏移植成功率

  近日，来自辛辛纳提大学的研究人员表明，一种新型的术前药物疗法相对传统方法而言可以减少肾脏病人机体中的抗体含量，从而有效增加患者肾脏移植的成功率及减少器官排斥的可能性，相关研究发表于国际杂志the American Journal of Transplantation上。
  抗体是机体免疫系统产生的用于抵御感染的蛋白质，但有时候抗体的产生往往是影响器官移植成功的屏障，本研究中，研究人员开发了一种针对移植候补病人的新型脱敏策略；研究者E. Steve Woodle博士表示，本研究对于改变传统的肾脏移植非常重要，其可使10%至20%的心脏和胰腺移植候选病人获益，而这些病人机体中往往存在较高水平的抗体从而使得移植受阻。
  自从2008年开始，研究人员就致力于开发靶向作用浆细胞的疗法，浆细胞可以产生抗体，最终研究人员开发出了以药物硼替佐米为基础的疗法，硼替佐米是一种FDA批准常用于治疗多发性骨髓瘤的蛋白酶抑制剂，传统的利用静脉注射免疫球蛋白的方法虽然可以降低机体的抗体水平，但对很多病人通常是无效的。
  本文中研究人员利用新策略治疗肾脏移植患者后，发现患者机体的抗体水平明显下降了，而且其低水平可以持续数月，这种新型的药物疗法被研究者命名为第二代血浆细胞靶向疗法，未来研究人员还需要进行更多的研究来优化这种药物疗法，来更大程度地改善肾脏移植患者的移植成功率。（转化医学网360zhyx.com）
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Prospective Iterative Trial of Proteasome Inhibitor-Based Desensitization
American Journal of Transplantation DOI: 10.1111/ajt.13050
E. S. Woodle1,*, A. R. Shields1,2, N. S. Ejaz1, B. Sadaka1, A. Girnita3, R. C. Walsh1, R. R. Alloway4, P. Brailey3, M. A. Cardi2, B. G. Abu Jawdeh4, P. Roy-Chaudhury4, A. Govil4 andG. Mogilishetty4
A prospective iterative trial of proteasome inhibitor (PI)-based therapy for reducing HLA antibody (Ab) levels was conducted in five phases differing in bortezomib dosing density and plasmapheresis timing. Phases included 1 or 2 bortezomib cycles (1.3 mg/m2 × 6–8 doses), one rituximab dose and plasmapheresis. HLA Abs were measured by solid phase and flow cytometry (FCM) assays. Immunodominant Ab (iAb) was defined as highest HLA Ab level. Forty-four patients received 52 desensitization courses (7 patients enrolled in multiple phases): Phase 1 (n = 20), Phase 2 (n = 12), Phase 3 (n = 10), Phase 4 (n = 5), Phase 5 (n = 5). iAb reductions were observed in 38 of 44 (86%) patients and persisted up to 10 months. In Phase 1, a 51.5% iAb reduction was observed at 28 days with bortezomib alone. iAb reductions increased with higher bortezomib dosing densities and included class I, II, and public antigens (HLA DRβ3, HLA DRβ4 and HLA DRβ5). FCM median channel shifts decreased in 11/11 (100%) patients by a mean of 103 ± 54 mean channel shifts (log scale). Nineteen out of 44 patients (43.2%) were transplanted with low acute rejection rates (18.8%) and de novo DSA formation (12.5%). In conclusion, PI-based desensitization consistently and durably reduces HLA Ab levels providing an alternative to intravenous immune globulin-based desensitization.