Department of Medicine B, Rabin Medical Center, Petah-Tikva, Israel.
Nephrology and Hypertension, Rabin Medical Center, Petah-Tikva, Israel.
Clin Transplant. 2019 Jun;33(6):e13562. doi: 10.1111/ctr.13562. Epub 2019 Apr 23.
Desensitization protocols have been developed in order to overcome the immunological barrier of donor-specific anti-HLA antibodies (DSA).
During 2006-2012, we implemented a program for desensitizing sensitized (positive DSA, negative NIH-CDC crossmatch) living-donor recipients. The long-term outcome of 36 sensitized recipients, treated with IVIG and plasmapheresis (PP), with or without rituximab (added when > 7500 MFI), was compared to 252 non-sensitized living-donor recipients.
Median peak DSA level before desensitization was 7223 (range 3567-16 000) MFI. During a mean follow-up of 121.9 months, graft loss occurred in 6/36 (17%) of the sensitized and 15/251 (6%) of the non-sensitized recipients (P = 0.021). Five-year and 10-year death-censored graft survival rates were 85% and 81% compared to 95% and 92%, respectively, for the non-sensitized recipients. There was no difference in recipients' survival. Slightly more episodes of acute rejection occurred in the sensitized group but had not influence on graft survival. At the last follow-up, 28 recipients had functioning graft; seventeen (47%) did not have detectable DSA. Eleven recipients had excellent graft function despite having detectable DSA.
The long-term outcomes of sensitized recipients who underwent desensitization are encouraging. Adding rituximab to PP + IVIG in candidates with very high titers may result in improved outcome.
为了克服供体特异性抗 HLA 抗体(DSA)的免疫屏障,已经开发了脱敏方案。
在 2006 年至 2012 年期间,我们实施了一项脱敏方案,用于治疗致敏(阳性 DSA,阴性 NIH-CDC 交叉配型)的活体供体受者。将 36 名接受 IVIG 和血浆置换(PP)治疗的致敏受者(当 MFI>7500 时添加利妥昔单抗)的长期结果与 252 名非致敏的活体供体受者进行比较。
脱敏前的中位峰值 DSA 水平为 7223(范围 3567-16000)MFI。在平均 121.9 个月的随访中,致敏组有 6/36(17%)的受者和非致敏组 15/251(6%)的受者发生移植物丢失(P=0.021)。5 年和 10 年无死亡移植物存活率分别为 85%和 81%,而非致敏组分别为 95%和 92%。受者存活率无差异。致敏组急性排斥反应的发生率略高,但对移植物存活率没有影响。在最后一次随访时,28 名受者有功能移植物;17 名(47%)没有检测到 DSA。尽管有可检测到的 DSA,但 11 名受者的移植物功能仍良好。
接受脱敏治疗的致敏受者的长期结果令人鼓舞。在滴度非常高的患者中,将利妥昔单抗添加到 PP+IVIG 中可能会改善结果。