Andreani Marco, Testi Manuela, Battarra Mariarosa, Indigeno Paola, Guagnano Annalisa, Polchi Paola, Federici Giorgio, Lucarelli Guido
Laboratorio di Immunogenetica e Biologia dei Trapianti, Fondazione IME, Roma, Italy.
Blood Transfus. 2008 Jul;6(3):143-9. doi: 10.2450/2008.0051-07.
Thalassaemia is a genetic disease that requires a hypertransfusion regimen to treat the anaemia caused by enhanced red blood cell destruction. The only radical cure for thalassaemia is to correct the genetic defect by bone marrow transplantation from an HLA-identical donor capable of producing and maintaining a normal haemoglobin level in the recipient. Complete donor haematopoiesis is not essential for sustained engraftment and the simultaneous presence of haematopoietic cells of both donor and recipient origin is not a rare event after a transplant.
The evolution of marrow engraftment of 93 transplanted thalassaemic patients, all from Middle East or Asian countries, was monitored by analysis of short tandem repeats.
Forty-three of 93 (46%) patients experienced a status of mixed chimerism early after bone marrow transplantation. Results of further engraftment analysis in these patients showed in 27 complete donor engraftment; rejection occurred in seven, while eight maintained the presence of both host and donor-derived cells. Interestingly, five out of the seven patients who rejected their transplant showed more than 25% residual host cells early after transplantation.
Our study confirmed that the presence of large amounts of residual host cells within the first 2 months after a transplant is a risk factor for graft rejection also in a group of patients with wide ethnic heterogeneity, irregular transfusion regimens and/or poor chelation treatment. Ten percent of the transplanted thalassaemic patients maintained coexistence of donor and recipient cells, showing a stable functional graft, characterized by normal production of beta globin chains and high levels of haemoglobin. A mechanism responsible for peripheral tolerance induction, such as the production of specific regulatory T-cell clones, seems to play a key role in the induction of long-term tolerance after the transplant.
地中海贫血是一种遗传性疾病，需要采用强化输血方案来治疗因红细胞破坏增加所导致的贫血。地中海贫血的唯一根治方法是通过来自 HLA 匹配供者的骨髓移植来纠正基因缺陷，该供者能够使受者产生并维持正常的血红蛋白水平。完全的供者造血对于持续植入并非必不可少，移植后供者和受者来源的造血细胞同时存在并非罕见现象。
通过分析短串联重复序列，对 93 例均来自中东或亚洲国家的接受移植的地中海贫血患者的骨髓植入情况进行了监测。
93 例患者中有 43 例（46%）在骨髓移植后早期出现混合嵌合状态。对这些患者进一步的植入分析结果显示，27 例实现了完全供者植入；7 例发生排斥反应，而 8 例维持了宿主和供者来源细胞的并存。有趣的是，7 例移植排斥患者中有 5 例在移植后早期显示有超过 25%的残留宿主细胞。
我们的研究证实，在一组具有广泛种族异质性、不规则输血方案和/或螯合治疗不佳的患者中，移植后前 2 个月内存在大量残留宿主细胞也是移植排斥的一个危险因素。10%的接受移植的地中海贫血患者维持了供者和受者细胞的共存，显示出稳定的功能性移植物，其特征为β珠蛋白链正常产生且血红蛋白水平高。一种负责诱导外周耐受的机制，如特定调节性 T 细胞克隆的产生，似乎在移植后长期耐受的诱导中起关键作用。
