Using Donor-Specific Antibodies to Monitor the Need for Immunosuppression
Using Donor-Specific Antibodies to Monitor the Need for Immunosuppression
复制标题
DOI：
10.1097/tp.0b013e31824f3d7c
复制
发表时间：
2012-06-15
期刊：
影响因子：
6.2
通讯作者：
Terasaki, Paul I.
中科院分区：
文献类型：
--
作者：
Hoshino, Junichi;Kaneku, Hugo;Terasaki, Paul I.
背景。经验表明，没有一个耐受方案是完美的，每一个逃避耐受必须及早发现，以防止移植物衰竭。此外，需要对停用免疫抑制（is）的患者进行一些检测，以警告断奶失败。常用的功能检测方法，如血清肌酐水平，不够灵敏，不能及时发现排斥反应。一项研究对72例接受活体肾移植的患者进行了研究，这些患者采用克隆删除方案（全淋巴细胞照射或硼替佐米），随后减少了维持IS的剂量。每个月或每2个月，使用Luminex混合和/或单一抗原珠进行供体特异性抗体（DSA）检测。移植后，17%的患者在6个月、41%的患者在1年、57%的患者在2年出现DSA， 95%可信限为10%、28%；30%、55%;分别是44%和71%。53%的患者在3个月内出现了DSA。此外，泼尼松剂量（每2.5 mg）和移植后年数与DSA产生呈负相关（风险比0.92[95%置信限：0.85,0.99]和0.70[0.49,1.00]）。DSA监测是非常有效的检测逃避耐受和重新出现的免疫反应在断奶患者。DSA的出现与断奶过程中维持药物的水平成反比。每月测量DSA足以检测免疫反应性的变化。
Background. Experience with tolerance protocols has shown that none is perfect and that each escape from tolerance must be identified early to prevent graft failure. In addition, some test is needed for patients who are weaned off immunosuppression (IS) to forewarn of weaning failure. The usual measures of function-such as serum creatinine levels-are not sensitive enough to detect rejection in a timely manner.Methods. A study was carried out on 72 patients who received living-donor kidney transplants with clonal deletion protocol (total lymphoid irradiation or bortezomib), and followed with reduced doses of maintenance IS. Every month or every 2 months, a test was performed for donor-specific antibodies (DSA) using Luminex mixed and/or single antigen beads.Results. After transplantation, DSA developed in 17% of the patients at 6 months, 41% at 1 year, and 57% at 2 years, with 95% confidence limits of 10%, 28%; 30%, 55%; and 44%, 71%, respectively. Fifty-three percent of patients weaned IS to less than 10 mg prednisone daily experienced DSA within 3 months. Furthermore, prednisone dose (per 2.5 mg) and years after transplantation were inversely associated with DSA production (risk ratio 0.92 [95% confidence limits: 0.85, 0.99], and 0.70 [0.49, 1.00].Conclusions. DSA monitoring is highly effective for detecting escape from tolerance and reemergence of the immune response in weaned patients. DSA appearance was inversely proportional to the level of maintenance drugs in the weaning process. Measurement of DSA on a monthly basis is adequate for detection of the change in immune reactivity.