Starzl T E, Demetris A J, Trucco M, Ricordi C, Ildstad S, Terasaki P I, Murase N, Kendall R S, Kocova M, Rudert W A
Pittsburgh Transplant Institute, University of Pittsburgh Health Science Center.
N Engl J Med. 1993 Mar 18;328(11):745-9. doi: 10.1056/NEJM199303183281101.
Liver transplantation for type IV glycogen storage disease (branching-enzyme deficiency) results in the resorption of extrahepatic deposits of amylopectin, but the mechanism of resorption is not known.
We studied two patients with type IV glycogen storage disease 37 and 91 months after liver transplantation and a third patient with lysosomal glucocerebrosidase deficiency (type 1 Gaucher's disease), in whom tissue glucocerebroside deposition had decreased 26 months after liver replacement, to determine whether the migration of cells from the allograft (microchimerism) could explain the improved metabolism of enzyme-deficient tissues in the recipient. Samples of blood and biopsy specimens of the skin, lymph nodes, heart, bone marrow, or intestine were examined immunocytochemically with the use of donor-specific monoclonal anti-HLA antibodies and the polymerase chain reaction, with preliminary amplification specific to donor alleles of the gene for the beta chain of HLA-DR molecules, followed by hybridization with allele-specific oligonucleotide probes.
Histopathological examination revealed that the cardiac deposits of amylopectin in the patients with glycogen storage disease and the lymph-node deposits of glucocerebroside in the patient with Gaucher's disease were dramatically reduced after transplantation. Immunocytochemical analysis showed cells containing the HLA phenotypes of the donor in the heart and skin of the patients with glycogen storage disease and in the lymph nodes, but not the skin, of the patient with Gaucher's disease. Polymerase-chain-reaction analysis demonstrated donor HLA-DR DNA in the heart of both patients with glycogen storage disease, in the skin of one of them, and in the skin, intestine, blood, and bone marrow of the patient with Gaucher's disease.
Systemic microchimerism occurs after liver allotransplantation and can ameliorate pancellular enzyme deficiencies.
肝移植治疗IV型糖原贮积病（分支酶缺乏症）可使肝外支链淀粉沉积吸收，但吸收机制尚不清楚。
我们研究了两名肝移植后37和91个月的IV型糖原贮积病患者，以及一名溶酶体葡萄糖脑苷脂酶缺乏症（1型戈谢病）患者，后者在肝移植26个月后组织葡萄糖脑苷脂沉积减少，以确定来自同种异体移植物的细胞迁移（微嵌合现象）是否可以解释受体中酶缺乏组织代谢的改善。使用供体特异性单克隆抗HLA抗体和聚合酶链反应对血液样本以及皮肤、淋巴结、心脏、骨髓或肠道的活检标本进行免疫细胞化学检查，首先对HLA-DR分子β链基因的供体等位基因进行特异性初步扩增，然后与等位基因特异性寡核苷酸探针杂交。
组织病理学检查显示，糖原贮积病患者心脏中的支链淀粉沉积以及戈谢病患者淋巴结中的葡萄糖脑苷脂沉积在移植后显著减少。免疫细胞化学分析显示，糖原贮积病患者的心脏和皮肤以及戈谢病患者的淋巴结（而非皮肤）中存在含有供体HLA表型的细胞。聚合酶链反应分析表明，两名糖原贮积病患者的心脏、其中一名患者的皮肤以及戈谢病患者的皮肤、肠道、血液和骨髓中均存在供体HLA-DR DNA。
肝同种异体移植后会出现全身微嵌合现象，并且可以改善全细胞酶缺乏症。
