Lee Iris, Constantinescu Serban, Gillespie Avrum, Rao Swati, Silva Patricio, Birkenbach Mark, Leech Stephen, Karachristos Andreas, Daller John A, Sifontis Nicole M
Departments of Medicine, Temple University School of Medicine, Philadelphia, Pennsylvania, USA.
Clin Transpl. 2010:397-403.
The effectiveness of current therapies for humoral rejection and decreasing antibody production directed against human leukocyte antigens (HLA) remains controversial. Standard regimens are unable to abrogate alloantibody production long term, most likely due to a lack of a direct effect on inhibiting and depleting mature plasma cells. Bortezomib (BZ) may be more effective at removing long-lived plasma cells compared to standard regimens that modulate alloantibody production by different mechanisms.
We report a kidney transplant recipient with several episodes of mixed antibody mediated and cellular rejection treated with numerous therapies including BZ. Monitoring included serial measurements of donor specific antibodies (DSA) by Luminex assay and repeated allograft biopsies.
One cycle of BZ was able to reverse humoral rejection and graft dysfunction. DSA levels to multiple donor HLA antigens which were not affected by previous therapies were reduced to undetectable levels post BZ. Abrogation of DSA was only transient. Despite continued stable renal function post-BZ, the patient had a reemergence of DSA, and evidence of humoral rejection detected by allograft biopsy.
Despite the promise of BZ as a therapy for humoral rejection, current data on how it should be used and its efficacy long-term remains limited.
目前针对体液排斥反应以及减少针对人类白细胞抗原（HLA）的抗体产生的治疗方法的有效性仍存在争议。标准治疗方案无法长期消除同种异体抗体的产生，这很可能是由于缺乏对抑制和清除成熟浆细胞的直接作用。与通过不同机制调节同种异体抗体产生的标准治疗方案相比，硼替佐米（BZ）在清除长寿浆细胞方面可能更有效。
我们报告了一名肾移植受者，其经历了多次混合抗体介导和细胞介导的排斥反应，接受了包括BZ在内的多种治疗。监测包括通过Luminex检测法对供体特异性抗体（DSA）进行系列测量以及重复进行移植肾活检。
一个周期的BZ能够逆转体液排斥反应和移植肾功能障碍。对多种供体HLA抗原的DSA水平在之前的治疗中未受影响，但在使用BZ后降至无法检测的水平。DSA的消除只是暂时的。尽管在使用BZ后肾功能持续稳定，但患者的DSA再次出现，并且通过移植肾活检检测到体液排斥反应的证据。
尽管BZ有望成为治疗体液排斥反应的方法，但目前关于其使用方式及其长期疗效的数据仍然有限。
