高剂量类固醇通过供体特异性输血导致的免疫耐受打破：肠道移植和心脏移植后的差异效应。

Break of tolerance via donor-specific blood transfusion by high doses of steroids: a differential effect after intestinal transplantation and heart transplantation.

作者信息

Koshiba T, Kitade H, Waer M, Mathieu C, Van Damme B, Pirenne J

机构信息

Abdominal Transplant Surgery Department, University Hospitals Leuven, Herestraat 49, B-3000 Leuven, Belgium.

出版信息

Transplant Proc. 2003 Dec;35(8):3153-5. doi: 10.1016/j.transproceed.2003.10.042.

DOI:10.1016/j.transproceed.2003.10.042

PMID:14698001

Abstract

UNLABELLED

Tolerance requires active mechanisms. How immunosuppressors affects tolerance is poorly understood.

METHODS

RA (RT1(p))/PVG (RT1(c)) rats were used as donor/recipient. Intestinal and heart transplant model were selected as highly and poorly immunogenic organs. Studied groups were 1, rejecting control; 2, received peritransplant steroids; 3, donor-specific blood transfusion (DSBT); 4, DSBT plus peritransplant steroids; and 5, DSBT+periDSBT Ste.

RESULTS

Intestinal transplant recipients in group 1 died on posttransplant day (d) 18. In group 2, steroids did not change survival (17 days, P >.05 versus group 1). With DSBT (group 3), all rats survived >75 days, whereas with steroids those in group 4 survived 59 days (P >.05 vs group 3) and group 5 survived 51 days (P <.05 versus group 3). Survivors in group 2 were tolerant as evidenced by acceptance of secondary donor-specific (not third-party) graft. However, 100% and 33% of donor-specific secondary grafts were rejected in groups 4 and 5 (P <.05 and P >.05 versus group 3). In heart transplants, steroid treatment had no effect on graft survival (group 1 9 days; group 2 9 days; P >.05). DSBT (group 3) induced 100% tolerance (primary: >100 days, secondary: 100%). Unlike in intestinal transplantation, adjunction peritransplant steroids (group 4) allowed 100% of primary and 83% of secondary graft acceptance (P >.05 versus group 3). In group 5, (DSBT+periDSBT steroids) acceptance of primary and secondary grafts tended to be reduced (primary: 77 days; P >.05 versus group 3; secondary: 67%, P >.05 versus group 3).

CONCLUSION

Steroid induction did not prolong graft survival after either intestinal or heart transplant. Adjunction of steroids to a DSBT tolerogenic regimen caused rejection of primary and secondary grafts, particularly after intestinal transplantation. Routine use of steroids in the clinics must be reconsidered, particularly when immunogenic organs are transplanted and when immunomodulation is applied.

摘要

未标记

耐受性需要主动机制。免疫抑制剂如何影响耐受性尚不清楚。

方法

将RA（RT1(p)）/PVG（RT1(c)）大鼠用作供体/受体。选择肠道和心脏移植模型作为免疫原性高和低的器官。研究组包括：1，排斥对照组；2，移植周围给予类固醇；3，供体特异性输血（DSBT）；4，DSBT加移植周围类固醇；5，DSBT+periDSBT类固醇。

结果

第1组肠道移植受体在移植后第18天死亡。第2组中，类固醇未改变生存率（17天，与第1组相比P>.05）。采用DSBT（第3组）时，所有大鼠存活超过75天，而采用类固醇时，第4组大鼠存活59天（与第3组相比P>.05），第5组存活51天（与第3组相比P<.05）。第2组的存活者具有耐受性，这通过接受二次供体特异性（而非第三方）移植物得到证明。然而，第4组和第5组中分别有100%和33%的供体特异性二次移植物被排斥（与第3组相比P<.05和P>.05）。在心脏移植中，类固醇治疗对移植物存活无影响（第1组9天；第2组9天；P>.05）。DSBT（第3组）诱导100%的耐受性（初次：>100天，二次：100%）。与肠道移植不同，移植周围给予类固醇（第4组）使100%的初次移植物和83%的二次移植物被接受（与第3组相比P>.05）。在第5组（DSBT+periDSBT类固醇）中，初次和二次移植物的接受率趋于降低（初次：77天；与第3组相比P>.05；二次：67%，与第3组相比P>.05）。