Macrochimerism in Intestinal Transplantation: Association With Lower Rejection Rates and Multivisceral Transplants, Without GVHD.
Macrochimerism in Intestinal Transplantation: Association With Lower Rejection Rates and Multivisceral Transplants, Without GVHD.
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DOI：
10.1111/ajt.13325
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发表时间：
2015-10
期刊：
影响因子：
--
通讯作者：
Sykes M
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文献类型：
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作者：
Zuber J;Rosen S;Shonts B;Sprangers B;Savage TM;Richman S;Yang S;Lau SP;DeWolf S;Farber D;Vlad G;Zorn E;Wong W;Emond J;Levin B;Martinez M;Kato T;Sykes M
据报道，在器官移植受者中有零星的血液嵌合现象，主要与移植物抗宿主病(GVHD)有关。我们假设，无论GVHD如何，多脏器移植(MVTx)受者的混合嵌合体程度将高于隔离肠道(IITx)和隔离肝移植(ILTx)的受者。我们进行了一项前瞻性的纵向研究，用流式细胞仪对移植后一年内的5名iITx和4名MVTx受者的多系血细胞嵌合性进行了研究。虽然只有1例iITx患者发生GVHD，但在9例iITx/MVTx受体中有8例检测到T细胞混合嵌合体。在表现出早期中度到重度排斥反应的四名受试者中，嵌合体显著较低。预先形成的高滴度供体特异性抗体，在体内与循环中的供体细胞结合，与嵌合体加速下降有关。对10名iLTx对照组的血液嵌合体也进行了研究。在非致敏患者中，接受MVTx的患者比接受iITx和iLTx的患者表现出更大的T和B细胞嵌合体。髓系嵌合体仅存在于iLTx和MVTx(6/13)受者中，提示它的存在需要肝移植。我们的研究首次证明，内脏移植后出现频繁的T细胞嵌合体，而非移植物抗宿主病，这可能与MVTx受者减少排斥反应有关。
Blood chimerism has been reported sporadically among visceral transplant recipients, mostly in association with graft-vs-host disease (GVHD). We hypothesized that a higher degree of mixed chimerism would be observed in multivisceral (MVTx) than in isolated intestinal (iITx) and isolated liver transplant (iLTx) recipients, regardless of GVHD. We performed a longitudinal prospective study investigating multilineage blood chimerism with flow cytometry in 5 iITx and 4 MVTx recipients up to one year post-transplant. Although only one iITx patient experienced GVHD, T-cell mixed chimerism was detected in 8 out of 9 iITx/MVTx recipients. Chimerism was significantly lower in the four subjects who displayed early moderate to severe rejection. Pre-formed high titer donor-specific antibodies, bound in vivo to the circulating donor cells, were associated with an accelerated decline in chimerism. Blood chimerism was also studied in 10 iLTx controls. Among non-sensitized patients, MVTx recipients exhibited greater T and B-cell chimerism than either iITx and iLTx recipients. Myeloid lineage chimerism was present exclusively among iLTx and MVTx (6/13) recipients, suggesting that its presence required the hepatic allograft. Our study demonstrates, for the first time, frequent T cell chimerism without GVHD following visceral transplantation and a possible relationship with reduced rejection rate in MVTx recipients.